ijerph International Journal of Environmental Research and Public Health 1661-7827 1660-4601 Molecular Diversity Preservation International (MDPI) 10.3390/ijerph7051913 ijerph-07-01913 Review Season of Birth and Risk for Adult Onset Glioma EfirdJimmy T. Center for Health of Vulnerable Populations, Office of the Dean, School of Nursing, University of North Carolina, 237A McIver Building, Administrative Drive, Greensboro, NC 27402-6170, USA; E-Mail: jimmy.efird@stanfordalumni.org; Tel.: +1-650-248-8282 5 2010 28 4 2010 7 5 1913 1936 6 1 2010 4 2 2010 11 2 2010 © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. 2010


Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive.

gliomas farming allergies handedness

Gliomas are a heterogeneous group of neoplasms in terms of cellular origin and location. They represent the most common malignant brain tumors [1]. Despite considerable efforts to unravel the etiologic basis for this cancer and attempts to find a cure, gliomas largely remain refractory to treatment. Except for a small percentage of cases, the tumors continue to show high morbidity and mortality. Established risk factors include ionizing radiation and a few genetic syndromes [2]. However, the attributable risk for these factors is small and can only explain a fraction of cases.

Evidence of an association between adult-onset glioma and date of birth suggests an etiologic role for a seasonally variable environmental exposure occurring prenatally around the time of birth. The period between an environmental exposure and the appearance of cancer may be lengthy, as illustrated by the development of vaginal cancer in daughters years after their mothers used diethylstilbestrol (DES) during pregnancy [3]. Similarly, exposure to asbestos 70 years prior to the development of mesothelioma [4], suggests a “one insult, co-carcinogenic model” of cancer development [5]. Risk factors that may exhibit seasonal epidemicity include exposure to infectious agents, allergens, pesticides, indoor environmental tobacco smoke, and other sources of polycyclic aromatic hydrocarbons (e.g., soot from fires for home heating), and use of antihistamines. Other putative candidates include harmonic variation in population mixing, diet, temperature, humidity, sunlight/photoperiod, levels of vitamin D3, and endogenous hormones [6,7].

The origins of many childhood and adult malignancies are believed to be determined during a finite perinatal window. During this period the brain and immune systems are less developed, undergoing greater cell growth and differentiation, and possibly more susceptible to DNA and epigenetic changes underlying cancer development in the near or distant future [5,813]. In this model, environmental exposures and lifestyle changes that occur afterwards play a mainly secondary role to the programming or imprinting that occurs during pregnancy and/or early infancy [14,15].

Methods Search Strategy

Articles were identified by systematically searching the Medline/PubMed database from inception to January 2010 using the key words: brain tumors and season of birth. Furthermore, we manually examined the bibliography of the papers that were identified electronically. We also searched for unpublished studies, PhD dissertations, internal reports, and conference proceedings/abstracts. Finally, to make our search inclusive of those studies in which season of birth was a secondary factor we checked the tables of every article known to us that examined risk factors for brain tumors. A similar process was used to identify papers on risk factors related to season of birth.

Inclusion Criteria

Studies were included only if the target population, outcome and exposures of interest were clearly defined and results were based on valid statistical methodology with evaluation of errors and discussion of study bias. Studies in which participants were chosen at convenience were not considered in this review. In the case of a cohort appearing in the literature multiple times only the most recent version was included since it provided the largest number of cases and the longest follow-up. Priority was given to papers that presented original data rather than reviews or meta-analyses.

Review of Literature

Several recent studies have explored season of birth as a risk factor for adult glioma, but results have been mixed (Table 1). Three independent reports have observed a peak risk for winter births [1618], while no seasonal variation for risk was noted in two other epidemiologic studies [19,20]. A multi-centered study of four Midwest states examining rural and farm exposures observed a statistically significant increased risk of adult gliomas for springtime births, but only among those born “off” a farm [21]. Similarly, the study of childhood brain tumors and season of birth have yielded equivocal results [2226].

Risk Factors Related To Season of Birth

The underlying rationale for the occurrence of a glioma decades after a seasonal exposure remains elusive. No specific etiologic agent to date has been identified to support such a long induction period for this cancer. Several hypothetical arguments have been offered in explanation of a season of birth effect for adult gliomas, if such an association exists. Thus far, the major evidence in support of a seasonal effect involves farming, allergies/immunity, viruses, and vitamin D. Other possible factors related to seasonal birth are diet, birth weight, and handedness.


Farming, by virtue of its seasonal nature, conveys increased risk at certain times of the year of exposure to pesticides and other agricultural chemicals. Insecticides and herbicides constitute the bulk of farm chemical exposures: two key routes of exposure are dermal and respiratory [27], bypassing detoxification in the liver. Many farm chemicals are classified as probable or likely human carcinogens by the US Environmental Protection Agency (EPA), most notably acephate, dichlorvos, dimethoate, lindane, parathion, phosmet, and tetrachlorvinphos [28].

Indoor exposures to these agents frequently occur [29,30]. Parents and other individuals track dust and dirt into the home, on shoes and clothes, after working on the farm. Household dust concentrations of azinphosmethyl, chlorpyrifos, parathion, and phosmet have been found to be significantly higher in farmer or farmworker homes than in referent homes [29]. Similarly, indoor-outdoor pets are efficient carriers of agents into the home, and also pose an exposure source for pesticides from anti flea/tick collars, sprays, and shampoos. Homes with high pet activities have been shown to have greater levels of pesticide residues in sampled carpet dust than homes with low pet activities [31,32]. Airborne farm pollutants also may enter the home environment by way of the wind, after spraying, gassing, or open-air application. Newborn and infant children have greater contact with these contaminants since they lie, crawl and play near the ground and frequently place their hands, objects or food in their mouths [29,33,34].

In tandem with living on a farm, infants have unique vulnerabilities that may lead to higher levels of exposures in the same environment than adults [9]. For example, their skin surface area is comparatively larger and more permeable to lipophilic compounds, which serves to maximize the absorption of compounds such as pesticides into the bloodstream [3537]. Dryness, rashes, and related skin conditions, to which infants may be particularly susceptible, serve to disrupt the protective barrier of the skin [36,38]. Once in the circulatory system, compounds enter the brain of the infant relatively quickly as the blood-brain barrier is not fully operational until at least 6 months of age [10].

At birth, children are less able to detoxify chemicals and other inorganic substances commonly used on farms [33,34], and they tend to have higher concentrations in their blood due to a decreased capacity to bind plasma protein [35]. They drink more water and eat more foods per unit of body weight than adults and will therefore ingest more toxins from well water and agriculturally treated foods [33,34]. Furthermore, they are more sensitive to airborne chemicals since their resting air intake is about twice that of an adult [34]. The commonly used organophospate pesticide chlorpyrifos (CPF) is known to specifically target the immature brain, from the early embryonic stage to the postweaning period, and it causes a host of irreversible changes to developing brain cells [39]. (Pesticides also are used outside the farm in urban schools, homes, and day-care centers for control of roaches, rats, and other vermin, and conceivably their peak period of application may differ seasonally from that on farms [33,40].)

While farmers live longer than the population-at-large [41], and die less frequently from cancer in general [42], several epidemiologic studies have found an increased risk for brain cancer in this group [4350]. Farmers represent a diverse group (e.g., with dairy, field crop, hog, beef cattle, poultry, fish, marijuana, cotton, and organic), and the heterogeneity of brain cancer risk for farmers could reflect differences in activities, as well as in the type, magnitude, and seasonality of exposures.

Allergies and Immunity

The perinatal period represents a time of heightened sensitivity to environmental allergens [51,52]. Within this window the peak for immune system priming or susceptibility is believed to vary differentially in response to presenting antigens [53,54]. Contact with allergens during early childhood may enhance the risk of developing allergies later in life, especially in individuals with a predisposition for atopic and allergic conditions [51,55].

Efforts to reduce allergen exposure immediately after birth often only delay the onset of allergic conditions, rather than preventing it, suggesting that immunologic memory may predate birth [15]. While genetics constitute a key determinant of immunologic memory and immune system maturation [5658], environmental factors also are believed to play an important role in the development of allergies, as illustrated by the discordance of allergies in twin studies [59], the increasing prevalence of atopic diseases over time [15,60], and the different incidence of allergies in immigrant and country of origin populations [61].

In a number of studies, season of birth has been associated with the development of allergic conditions later in life, such as asthma [6165], atopic dermatitis [66], house dust mite allergy [60,61,65,6769], cockroach allergy [70,71], grass/birch/hay and other pollen allergy [51,60,63,67, 68,7276], animal dander allergy [51,67], mold allergy [74], food allergy [51,55,67], allergic rhinitis [62,77], and otherwise unspecified atopy (NOS) [55,78]. In the case of cockroach sensitivity, over 60% of inner-city residents with asthma test positive for cockroach allergen [79], with black children and those receiving public assistance most likely to be sensitized [70]. The rate of cockroach sensitization at the age of 5 years was higher for winter births (72%), than for spring (48%), summer (42%) and fall (43%) births [70].

Factors known to influence the development of asthma include race [80,81], low yearly family income [81], less than a high school education [81], residence in high poverty areas [81], exposure to urban air pollution [64] and childhood viral infections [64,82]. A significant percent of infants with a history of respiratory syncytial virus (RSV) bronchiolitis infection, which peaks during the winter season, develop asthma [64].

Asthma, allergies, and other atopic diseases have been inversely associated with adult glioma risk in several epidemiologic studies and meta-analyses [8393], although some reports do not support this conclusion [9498]. The exact biologic mechanisms underlying a protective effect are not clearly understood. It has been suggested that the inverse association may reflect increased immune surveillance on the part of the atopic individual [91,93]. Glioma patients are known to suffer from an impaired immune system [99], and the reduced association with allergies alternatively could be due to immunosuppression induced by the tumor (i.e., reverse causality) [84]. Inflammatory responses also may favor tumor development [93]. In animal studies, therapeutic immunity to intracranial tumors has been induced by peripheral immunization with interleukin-4 (IL-4) transduced glioma cells [100,101].

Being raised on a farm [102114] or in a rural area [115] has been shown in some studies to protect against asthma, hay fever, and atopic sensitization. Although farm children are exposed to higher concentrations of airborne allergens, paradoxically they become sensitized less often and manifest a weaker sensitization response than non-farm controls [113]. Some researchers have hypothesized that the protective effect may be attributed to a form of “tolerance”. Such tolerance could conceivably develop early in life, following repeated exposure to high levels of allergens such as organic dusts, fungi, and endotoxins; this is perhaps the result of component lipopolysaccharides that excite Th1 responses and suppress the development of immunoglobulin-E (IgE)-antibodies [109,116].

Little is known about specific determinants of asthma and atopy in the farm setting. Any relationship with glioma risk is probably complex and must be interpreted in light of differences in farming practices and the protective ability of farming environments, especially with respect to microbial exposures [102,103,114]. While farmers and their families have greater contact with seasonal elements, they may be less prone to “sick building syndrome” than residents of urban areas [117]. The latter tend to live and work in a more closed indoor environment and thus suffer greater exposure to indoor pollutants (e.g., polychlorinated biphenyls, phthalates, phenols, flame retardants) [29]. Other mitigating factors may include a greater intake of saturated fat in the form of milk and butter, as well as a greater number of older siblings living at home in rural/farm communities [116]. Furthermore, farmers usually are non-smokers and healthier than the population-at-large [43,116,118120]. By self-selection, those who manifest seasonal allergies may choose a career path other than farming (i.e., healthy worker effect) [116].

Differences in the definition of atopy, a lack of objective measures of atopy, residual confounding, and bias (e.g., detection, selection, interview, recall) are important to consider when interpreting the above studies [92,121]. Furthermore, regarding the role of allergies and immunity, there is no clear trend toward a decreasing risk for glioma with younger ages at onset of the allergic condition [121].

Interestingly, increased risk for glioma has been observed in patients with AIDS-related immuno-suppression [122124], but not in those with iatrogenic immuno-suppression [125].


Environmental exposures to viruses, microbes and other pathogens generally tend to occur more often in particular seasons [25,126,127]. Polyomaviruses have been shown to induce brain tumors in animals [128131] and have been detected in human gliomas [132]. Other neuro-oncogenic viruses implicated in gliomas under laboratory conditions include human adenovirus type 12 and Rous sarcoma virus [133]. Some tumor viruses must be injected in animals on the first day of life to be effective, although they may not cause cancer until years later [7].

Epidemiologic evidence in support of a viral or pathogenic etiology for adult brain tumors remains controversial and the windows of interest of these studies have been outside the perinatal period. In adults, Toxoplasma gondii infection has been associated with a greater prevalence of astrocytomas [134], while decreased glioma risk has been associated with a history of infections/colds [88], and chicken pox [135,136]. On the other hand, increased risk for childhood brain tumors has been associated in some studies with a history of chicken pox [137], influenza [138,139], measles [138], general viral infections [140,141], and neonatal urinary tract infections [141]. In particular, a 7.5-fold OR (95% CI = 1.3–44.9) for low grade astrocytoma has been observed for neonatal urinary tract infections [141]. Bacterial urinary tract infections have been shown to follow a well defined seasonal pattern with a peak in August [127]. Similarly, seasonal occurrence has been observed for chicken pox, measles, influenza and many other common childhood infectious diseases [7,142].

A seasonal infectious etiology for disease is complicated by many factors [126]. The same infectious agent may present a different pattern of incidence depending on the host location. A seasonal peak evident in the general population may not behave uniformly within certain subpopulations. Temperature, humidity, precipitation, and indoor air quality are among the mitigating factors that may affect the survival and transmissibility of a pathogen and explain different seasonal peaks for a disease in different studies. Other factors include poor nutrition, crowding, seasonal travel, hygiene practices, cultural practices in food consumption/preparation, changes in herd immunity, or evolution of the infectious agent over time. Furthermore, seasonal variation in immune function may increase host susceptibility to infections at certain times of the year [143,144]. Given the rarity of some infections and brain tumors, the interpretability of seasonal patterns, or the lack thereof, may be confounded by time- and/or space-dependent factors [126].

Vitamin D

Vitamin D is a fat-soluble prohormone which operates via a nuclear receptor [145]. Maternal serum vitamin D levels tend to be closely correlated with infant cord serum levels [146,147]. This light synthesized steroid, resulting from the absorption of ultraviolet B photons by 7-dehydrocholesterol in the skin [148], has been suggested as a possible factor underlying the season of birth risk for adult gliomas observed in some studies [145]. Levels of vitamin D are known to fluctuate depending on sunlight exposure, which is highest in the summer for the northern hemisphere and tends to increase for latitudes nearer the equator [145,148150].

Antiproliferative and proapoptotic activity of vitamin D3 has been noted in model glioma cell lines and a primary culture, as well as tumor tissue experiments [145]. Further, prenatal vitamin D3 depletion has been associated with altered brain development in rodent studies [151]. Vitamin D receptors are present in most cells and tissues in the body [152], including the brain [148], so this hormone is believed to play an important role in disease management and cancer prevention as a modulator of immune system activity [148,153155].

Children who live in polluted, inner city environments and who are deprived of regular sunlight exposure have been shown to suffer a higher prevalence of rickets (due to vitamin D deficiency) than children in rural areas [148]. Seasonal variation in vitamin D levels also has been suggested as a factor differentially affecting newborn growth plate width, and this may explain why babies born in Australia around October (spring) are relatively heavier than those born at other times [156].


The “developmental plasticity hypothesis” refers to the critical developmental period in utero when the fetus is plastic and adaptively imprints to its environment. In utero adaptation may lead to lifelong changes in the body’s metabolism, hormone regulation, and the number of cells present in key organs [14,157,158]. If this is the case, adult health outcomes may reflect season of birth if food intake is seasonal, and if exposure occurs at a critical stage of fetal development. Certain foods and the chemicals contained in these foods may be more or less available at particular times of the year due to crop cycles, storage capability, transportation access, and cost; and the use of preservatives in foods also may vary accordingly. N-nitroso compounds are a potent inducer of cancer and brain tumors in various animal species [159,160], and fetal exposure produces more tumors than postnatal exposure [161]. Foods high in N-nitroso compounds have been associated with an increased risk for brain tumors in some studies [162165]. These compounds may be present in foods through their use as preservatives or in fertilizers [166].

Vitamin C, which is mostly found in seasonal fruits and vegetables, can react with and then inhibit nitrite formation of nitrosamines [163]. An 18-fold greater risk of primary adult brain tumors has been found among individuals who consumed large amounts of processed meats (high in N-nitroso content) and drank orange/grapefruit juice once per week or less, than among those who consumed less processed meat and drank orange/grapefruit juice more often [164]. However, a recent multi-centered international case-control study of adult diet and brain tumor risk found no evidence of confounding or effect modification by vitamin supplementation, especially in the association between consumption of cured meats (containing high levels of nitrates) and gliomas [167].

Birth Weight

Birth weight has been reported to vary by season of birth [168170]. High birth weight is an important predictor of adult obesity [171], and a higher body mass index (BMI) has been linked to greater risk for adult-onset glioma [172]. In children, high birth weight has been associated with increased risk for astrocytoma and medulloblastoma/primitive neuroectodermal tumors (PNET) [173]. Temporal patterns in birth weight may result from seasonal variations in food availability. For example, birth weights in agricultural societies are highest at the peak of the dry season, corresponding to the time of harvesting and greatest food availability [174]. Interestingly, very low birth weight has been associated with left- or mix-handedness [175,176], a factor associated in some studies with season of birth [177] and reduced glioma risk [178].


Handedness is believed to be determined in utero [179], possibly through hormonal influences [180183], and has been linked with immune disease [184,185], various developmental learning disorders [184], epilepsy [186], and breast cancer risk in both pre- and post-menopausal women [187190]. Exposure to a high level of testosterone during the earlier part of pregnancy is thought to promote right brain development and influence hand preference, although the evidence in support of a relationship is not conclusive [191]. Testosterone, progesterone, oestradiol, and lutenising hormone levels in women have been reported to be higher in spring than in autumn [192194].

Results from several studies hint that non-genetic factors may play an important role in the determination of handedness. Women exposed in utero to the estrogen-like compound DES show a higher prevalence for left handedness [195,196]. Similarly, left-handedness has been linked to congenital adrenal hyperplasia, a condition characterized by high in utero levels of androgeizing hormones [197]. Of note, brain tumors are known to contain sex steroid receptors (e.g., estrogen, androgen, progestin) [198], and sex hormones have been shown to promote brain tumors in animal studies [199,200]. Mice reared under conditions favoring the right limb develop a right-limb preference, and vice versa [201], further suggesting that environmental factors influence handedness. Additionally, the discordance of handedness in twin studies illustrates that genetics alone cannot explain the development of handedness [202207].

Handedness has been shown to follow a gender-invariant seasonal pattern, with more left-handers than right-handers born between March and July [177,178]. Being right-handed has been associated with a greater risk for glioma than being left-handed or ambidextrous [178]. However, for left-handed and ambidextrous participants born from late fall through early spring, glioma risk also has been shown to be higher than for those born at other times of the year [16]. A study of 15,390 Brazilian students was unable to detect a difference in the season of birth between right- and left-handers. However, little seasonal variation exists in the light/dark cycle in the area where the majority of study participants were born [208].

The putative connection between handedness, season of birth, and glioma risk remains difficult to interpret. For example, glioma risk is greater for males than females [2], yet the pattern of seasonal influence upon handedness does not vary significantly between females and males [177]. A higher incidence of sinistrality has been observed for individuals born in winter and autumn than for those born summer and spring [191]. The incidence of left-handedness is disproportionately higher among males [202], a finding which is consistently observed across species [201,209212]. Risk for glioma also is nearly equal for left-handed and ambidextrous individuals but higher for right-handers. Overall, handedness appears to be a surrogate marker for an underlying but unidentified risk factor that interacts with seasonality and other factors to possibly explain glioma risk.


Season of birth in its own right cannot be deemed a cause for glioma. Rather, it is a surrogate marker for underlying risk factors that may offer subtle clues about the possible perinatal etiology of adult gliomas.

There is probably no specific etiologic agent acting in isolation that completely explains a season of birth association with adult glioma risk. If an association exists the effect probably represents the interplay between various environmental, genetic, lifestyle, and socioeconomic factors, operating on mother and child within a precise window of vulnerability. The mechanism of action may involve epigenetic processes or DNA changes with the capacity to modulate or influence oncogenic outcomes in the distant future. A patient’s innate and adaptive immune response and a host of hormonal and metabolic factors, likely play important and closely interrelated roles in understanding the complex biologic and etiologic mechanisms in the season of birth effect for adult gliomas.

In the studies conducted to date, risk estimates and p-values for the association between season of birth and glioma risk have been nominal to borderline in strength. However, a weak association does not necessarily imply the absence of causality, nor is a strong association necessary or sufficient for causality [213,214]. The ability to find associations between specific seasonal risk factors occurring around the time of birth and adult glioma incidence is limited by the rarity of this cancer in the population and the vast time period from exposure to disease. While the risk factors outlined in this review do not conflict with our current understanding of the natural history of cancer or glioma specifically, the evidence in support of a causal relationship has not been consistent. To some degree, effect modification or publication bias may explain the inconsistencies. At minimum, if a causal relationship exists, season of birth meets the criteria of temporality as the period surrounding birth clearly predates disease occurrence. However, the exact window of exposure when the underlying risk factor(s) most occur to cause disease is unknown.

On the present evidence, it is not possible to definitively answer the question of how season of birth influences glioma risk, or to favor any specific hypothesis. Many questions remain and future research will benefit from focused studies aimed at specific exposures and subpopulations, allowing for more detailed analyses by histologic subtypes.

This manuscript was made possible by a grant from NCMHD/NIH (P20MD002289) entitled “Teamwork in Research and Intervention to Alleviate Disparities Project (TRIAD)”. Elizabeth Tornquist (UNC-CH) and Debra C. Wallace (UNCG) offered valuable comments during the writing of this manuscript and their knowledge and insight are greatly appreciated. The author also thanks Helen Sedwick, Caitlin Fehrenbacher and Carol Zurcher for administrative and proofreading assistance, and Ruirui Jiang for carefully checking references. The contents of this publication are solely the responsibility of the author and do not necessarily represent the views of any funding agency.

References CBTRUS Statistical ReportPrimary Brain Tumors Diagnosed in the United States in 2004–2005Central Brain Tumor Registry of the United StatesHinsdale, IL, USA2009 WrenschMMinnYChewTBondyMBergerMEpidemiology of primary brain tumors: Current concepts and review of the literatureNeuro. Oncol20024278299 HerbstAUlfelderHPoskanzerDAdenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young womenN. Engl. J. Med1971284878881 McDonaldAMcDonaldJEpidemiologic surveillance of mesothelioma in CanadaCan. Med. Assoc. J1973109359362 PolednakALatency periods in neoplastic diseasesAm. J. Epidemiol1974100354356 EfirdJNielsenSA method to model season of birth as a surrogate environmental risk factor for diseaseInt. J. Environ. Res. Public Health200854953 BailarJGurianJMonth of birth and cancer mortalityJ. Natl. Cancer Inst196433237242 RiceJWardJAge dependence of susceptibility to carcinogenesis in the nervous systemAnn. N.Y. Acad. Sci1982381274289 SelevanSKimmelCMendolaPIdentifying critical windows of exposure for children’s healthEnviron. Health Perspect2000108451455 RodierPDeveloping brain as a target of toxicityEnviron. Health Perspect19951037376 RodierPVulnerable periods and processes during central nervous system developmentEnviron. Health Perspect1994102121124 FeinbergAOhlssonRHenikoffSThe epigenetic progenitor origin of human cancerNat. Rev. Genet200672133 LundALohuizenMEpigenetics and cancerGenes Dev20041823152335 BarkerDThe developmental origins of adult diseaseEur. J. Epidemiol200318733736 WarnerJJonesCJonesAWarnerJPrenatal origins of allergic diseaseJ. Allergy Clin. Immunol2000105S493S496 BrennerALinetMShapiroWSelkerRFineHBlackPInskipPSeason of birth and risk of brain tumors in adultsNeurology200463276281 KochHKlinkhammer-SchalkeMHofstädterFBogdahnUHauPSeasonal patterns of births in patients with glioblastomaChronobiol. Int20062310471052 MainioAHakkoHKoivukangasJNiemeläARäsänenPWinter birth in association with a risk of brain tumor among a Finnish patient populationNeuroepidemiology2006275760 StaykovDRadespiel-TrögerMMeyerMPetschSSchwabSHandschuRBirth month and risk of glioma in adults: a registry-based study in BavariaChronobiol. Int200926282292 HoubenMCoeberghJBirchJTijssenCvan DuijnCMcNallyRSpace-time clustering patterns of gliomas in the Netherlands suggest an infectious aetiologyEur. J. Cancer20054129172923 EfirdJSeason of birth and risk for adult gliomas (abstract)Brain Tumor Epidemiology Consortium Annual Meeting Abstract SessionThe Houstonian Hotel, Houston, Texas4–6 April, 2009 McNallyRCairnsDEdenOAlexanderFTaylorGKelseyGBirchJAn infectious aetiology for childhood brain tumours? Evidence from space-time clustering and seasonality analysesBr. J. Cancer20028610701077 HeuchJHeuchIAkslenLKvåleGRisk of primary childhood brain tumors related to birth characteristics: a Norwegian prospective studyInt. J. Cancer199877498503 YamakawaYFukuiMKinoshitaKOhgamiSKitamuraKSeasonal variation in incidence of cerebellar medulloblastoma by month of birthFukuoka Igaku Zasshi197970295300 HoffmanSSchellingerKProppJMcCarthyBCampbellRDavisFSeasonal variation in incidence of pediatric medulloblastoma in the United States, 1995–2001Neuroepidemiology2007298995 HalperinEMirandaMWatsonDGeorgeSStanberryMMedulloblastoma and birth date: evaluation of 3 U.S. datasetsArch. Environ. Health2004592630 NielsonJNielsonFSørensenJIn vitro percutaneous penetration of five pesticides—effects of molecular weight and solubility characteristicsAnn. Occup. Hyg200448697705 Chemicals evaluated for carcinogenic potentialOffice of Pesticide Programs, Health Effects Division, US Environmental Protection AgencyWashington, DC, USAApril 2003. ButteWHeinzowBPollutants in house dust as indicators of indoor contaminationRev. Environ. Contam. Toxicol2002175146 StarrHAldrichFMacDougallWMounceLContribution of household dust to the human exposure to pesticidesPestic. Monit. J19748209212 MorganMStoutDWilsonNFeasibility study of the potential for human exposure to pet-borne diazinon residues following lawn applicationsBull. Environ. Contam. Toxicol200166295300 NishiokaMBurkholderHBrinkmanMLewisRDistribution of 2,4-Dichlorophenoxyacetic acid in floor dust throughout homes following homeowner and commercial lawn applications: quantitative effects of children, pets, and shoesEnviron. Sci. Technol19993313591365 LandriganPClaudioLMarkowitzSBerkowitzGBrennerBRomeroHWetmurJMatteTGoreAGodboldJWolffMPesticides and inner-city children: exposures, risks, and preventionEnviron. Health Perspect1999107431437 LandriganPRisk assessment for children and other sensitive populationsAnn. N.Y. Acad. Sci199989519 WestDWorobecSSolomonLPharmacology and toxicology of infant skinJ. Invest. Dermatol198176147150 FenskeRBlackKElknerKLeeCMethnerMSotoRPotential exposure and health risks of infants following indoor residential pesticide applicationsAm. J. Public Health199080689693 WesterRMaibachHIn vivo percutaneous absorption and decontamination of pesticides in humansJ. Toxicol. Environ. Health1985162537 NielsenJPercutaneous penetration through slightly damaged skinArch. Dermatol. Res2005296560567 GarciaSSeilderFSlotkinTDevelopmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: effects on neurospecific proteins indicate changing vulnerabilitiesEnviron. Health Perspect2003111297303 AdgateJKukowskiAStroebelCShubatPMorrellSQuackenbossJWhitmoreRSextonKPesticide storage and use patterns in Minnesota households with childrenJ. Expo. Anal. Environ. Epidemiol200010159167 AlavanjaMSandlerDMcMasterSZahmSMcDonnellCLynchCPennybackerMRothmanNDosemeciMBondABlairAThe Agricultural Health StudyEnviron. Health Perspect1996104362369 BlairADosemeciMHeinemanECancer and other causes of death among male and female farmers from twenty-three statesAm. J. Ind. Med199323729742 KristensenPAndersenAIrgensLLaakePByeAIncidence and risk factors of cancer among men and women in Norwegian agricultureScand. J. Work Environ. Health1996221426 ReifJPearceNFraserJOccupational risks for brain cancer: a New Zealand cancer registry-based studyJ. Occup. Med198931863867 WingrenGAxelsonOCluster of brain cancers spuriously suggesting occupational risk among glassworkersScand. J. Work Environ. Health1992188589 AhlbomANavierINorellSOlinRSpännareRNonoccupational risk indicators for astrocytomas in adultsAm. J. Epidemiol1986124334337 MusiccoMFilippiniGBordoBMelottoAMorelloGBerrinoFGliomas and occupational exposure to carcinogens: case-control studyAm. J. Epidemiol1982116782790 MusiccoMSantMMolinariSFilippiniGGattaGBerrinoFA case-control study of brain gliomas and occupational exposure to chemical carcinogens: the risk to farmersAm. J. Epidemiol1988128778785 BrownsonRReifJChangJDavisJAn analysis of occupational risks for brain cancerAm. J. Public Health199080169172 HeinemanEGaoYDosemeciMMcLaughlinJOccupational risk factors for brain tumors among women in Shanghai, ChinaJ. Occup. Environ. Med199537288293 NilssonLBjörksténBHattevigGKjellmanBSigursNKjellmanNSeason of birth as predictor of atopic manifestationsArch. Dis. Child199776341344 WarnerJJonesCJonesAMilesEFrancisTWarnerJImmune responses during pregnancy and the development of allergic diseasePediatr. Allergy Immunol19978510 Van Duren-SchmidtKPichlerJEbnerCBartmannPFörsterEUrbanekRSzépfalusiZPrenatal contact with inhalant allergensPediatr. Res199741128131 JonesAMilesEWarnerJColwellBBryantTWarnerJFetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestationPediatr. Allergy Immunol19967109116 NilssonLKjellmanNAtopy and season of birthAllergy199651138139 DoldSWjstMvon MutiusEReitmeirPStiepelEGenetic risk for asthma, allergic rhinitis, and atopic dermatitisArch. Dis. Child19926710181022 KüsterWPetersenMChristophersEGoosMSterryWA family study of atopic dermatitis: clinical and genetic characteristics of 188 patients and 2,151 family membersArch. Dermatol. Res199028298102 OberCHoffjanSAsthma genetics 2006: the long and winding road to gene discoveryGenes Immun2006795100 FalliersCde CardosoRBaneHCoffeyRMiddletonEDiscordant allergic manifestations in monozygotic twins: genetic identity versus clinical, physiologic, and biochemical differencesJ. Allergy197147207219 BusincoLCantaniAFarinellaFBusincoEMonth of birth and grass pollen or mite sensitization in children with respiratory allergy: a significant relationshipClin. Allergy198818269274 SmithJSpringettVAtopic disease and month of birthClin. Allergy19799153157 ÅbergNBirth season variation in asthma and allergic rhinitisClin. Exp. Allergy198919643648 WjstMDoldSReitmeirPStiepelEvon MutiusEMonth of birth and allergic disease at the age of 10Clin. Exp. Allergy19922210261031 GazalaERon-FeldmanVAltermanMKamaSNovackLThe association between birth season and future development of childhood asthmaPediatr. Pulmonol20064111251128 WarnerJPriceJHouse dust mite sensitivity in childhood asthmaArch. Dis. Child197853710713 LewyHMeirsonHLarsonZSeasonality of birth month of children with celiac disease differs from that in the General population and between sexes and is linked to family history and environmental factorsJ. Pediatr. Gastroenterol. Nutr200948181185 AalberseRNieuwenhuysEHeyMStapelS‘Horoscope effect’ not only for seasonal but also for non-seasonal allergensClin. Exp. Allergy19922210031006 SoothillJStokesCTurnerMNormanATaylorBPredisposing factors and the development of reaginic allergy in infancyClin. Allergy19766305319 KorsgaardJDahlRSensitivity to house dust mite and grass pollen in adults: influence of the month of birthClin. Allergy198313529535 SarpongSKarrisonTSeason of birth and cockroach allergen sensitization in children with asthmaJ. Allergy Clin. Immunol1998101566568 LendorCJohnsonAPerzanowskiMChewGGoldsteinIKelvinEPereraFMillerREffects of winter birth season and prenatal cockroach and mouse allergen exposure on indoor allergen-specific cord blood mononuclear cell proliferation and cytokine productionAnn. Allergy Asthma Immunol2008101193199 BjörksténFSuoniemiIKoskiVNeonatal birch-pollen contact and subsequent allergy to birch pollenClin. Allergy198010585591 PearsonDFreedDTaylorGRespiratory allergy and month of birthClin. Allergy197772933 QuoixEBessotJKopferschmitt-KublerMFraissePPauliGPositive skin tests to aero-allergens and month of birthAllergy198843127131 KempARelationship between the time of birth and the development of immediate hypersensitivity to grass-pollen antigensMed. J. Aust19791263264 RobertJCarronRPollinose precoce des natifs du taureau (Early pollen allergy in children born in spring)Rev. Franc. Allergol197919153155 PedersenPWeekeEMonth of birth in asthma and allergic rhinitisScand. J. Prim. Health Care1983197101 CronerSKjellmanNPredictors of atopic disease: cord blood IgE and month of birthAllergy1986416870 SarpongSHamiltonREgglestonPAdkinsonNSocioeconomic status and race as risk factors for cockroach allergen exposure and sensitization in children with asthmaJ. Allergy Clin. Immunol19969713931401 McDanielMPaxsonCWaldfogelJRacial disparities in childhood asthmas in the United States: evidence from the National Health Interview Survey, 1997 to 2003Pediatrics2006117e868e877 LitonjuaACareyVWeissSGoldDRace, socioeconomic factors, and area of residence are associated with asthma prevalencePediatr. Pulmonol199928394401 FrickOGermanDMillsJDevelopment of allergy in children. I. Association with virus infectionsJ. Allergy Clin. Immunol197963228241 Berg-BerkhoffGSchüzJBlettnerMMünsterESchlaeferKWahrendorfJSchlehoferBHistory of allergic disease and epilepsy and risk of glioma and meningioma (INTERPHONE study group, Germany)Eur. J. Epidemiol200924433440 WigertzALönnSSchwartzbaumJHallPAuvinenAChristensenHJohansenCKlæboeLSalminenTSchoemakerMSwerdlowATynesTFeychtingMAllergic condition and brain tumor riskAm. J. Epidemiol2007166941950 SchwartzbaumJJonssonFAhlbomAPreston-MartinSLönnSSöderbergKFeychtingMCohort studies of association between self-reported allergic conditions, immune-related diagnoses and glioma and meningioma riskInt. J. Cancer2003106423428 HochbergFTonioloPColePNonoccupational risk indicators of glioblastoma in adultsJ. Neurooncol199085560 SchlehoferBBlettnerMBeckerNMartinsohnCWahrendorfJMedical risk factors and the development of brain tumorsCancer19926925412547 SchlehoferBBlettnerMPreston-MartinSNiehoffDWahrendorfJArslanAAhlbomAChoiWGilesGHoweGLittleJMénégozFRyanPRole of medical history in brain tumour development. Results from the international adult brain tumour studyInt. J. Cancer199982155160 RyanPLeeMNorthBMcMichaelARisk factors for tumors of the brain and meninges: results from the Adelaide Adult Brain Tumor StudyInt. J. Cancer1992512027 BrennerALinetMFineHShapiroWSelkerRBlackPInskipPHistory of allergies and autoimmune diseases and risk of brain tumors in adultsInt. J. Cancer200299252259 LinosERaineTAlonsoAMichaudDAtopy and risk of brain tumors: a meta-analysis. JNatl. Cancer Inst20079915441550 WangHDiepgenTIs atopy a protective or a risk factor for cancer? A review of epidemiological studiesAllergy20056010981111 CarrozziLViegiGAllergy and cancer: a biological and epidemiological rebusAllergy20056010951097 HagströmerLYeWNyrénOEmtestamLIncidence of cancer among patients with atopic dermatitisArch. Dermatol200514111231127 TurnerMChenYKrewskiDGhadirianPThunMCalleECancer mortality among US men and women with asthma and hay feverAm. J. Epidemiol2005162212221 SiegmundBSchlehoferBWahrendorfJInvestigation on primary brain tumours and the co-morbidity with diabetes mellitus and atopic diseases in frame of the EPIC studyBrain Tumor Epidemiology Consortium Annual Meeting Abstract Session, German Cancer Research Center, Heidelberg, Germany, 5–7 April, 2008. ErikssonNMikoczyZHagmarLCancer incidence in 13811 patients skin tested for allergyJ. Investig. Allergol. Clin. Immunol200515161166 CicuttiniFHurleySForbesADonnanGSalzbergMGilesGMcNeilJAssociation of adult glioma with medical conditions, family and reproductive historyInt. J. Cancer199771203207 DixABrooksWRoszmanTMorfordLImmune defects observed in patients with primary malignant brain tumorsJ. Neuroimmunol1999100216232 OkadaHVillaLAttanucciJErffMFellowsWLotzeMPollackIChambersWCytokine gene therapy of gliomas: effective induction of therapeutic immunity to intracranial tumors by peripheral immunization with interleukin-4 transduced glioma cellsGene Ther2001811571166 BenedettiSDi MecoFCireneiNBruzzoneMPolloBFlorioNCaposioLColomboMCattaneoEFinocchiaroGIL-4 gene transfer for the treatment of experimental gliomasAdv. Exp. Med. Biol1998451315321 AlfvenTBraun-FahrländerCBrunekreefBvon MutiusERiedlerJScheyniusAvan HageMWickmanMBenzMBuddleJMichelsKSchramDUblaggerEWaserMPershagenGthe PARSIFAL study groupAllergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle—the PARSIFAL studyAllergy200661414421 EgeMFreiRBieliCSchram-BijkerkDWaserMBenzMWeissGNybergFvan HageMPershagenGBrunekreefBRiedlerJLauenerRBraun-FahrländerCvon MutiusEthe PASIFAL Study teamNot all farming environments protect against the development of asthma and wheeze in childrenJ. Allergy Clin. Immunol200711911401147 RiedlerJBraun-FahrländerCEderWSchreuerMWaserMMaischSCarrDSchierlRNowakDvon MutiusEthe ALEX Study TeamExposure to farming in early life and development of asthma and allergy: a cross-sectional surveyLancet200135811291133 Braun-FahrländerCGassnerMGrizeLNeuUSennhauserFVaronierHVuilleJWäthrichBThe SCARPOL TeamPrevalence of hay fever and allergic sensitization in farmer’s children and their peers living in the same rural communityClin. Exp. Allergy1999292834 RiedlerJEderWOberfeldGSchreuerMAustrian children living on a farm have less hay fever, asthma and allergic sensitizationClin. Exp. Allergy200030194200 von EhrensteinOvon MutiusEIIIiSBaumannIBöhmBvon KriesRReduced risk of hay fever and asthma among children of farmersClin. Exp. Allergy200030187193 KilpelainenMTerhoEHeleniusHKoskenvuoMFarm environment in childhood prevents the development of allergiesClin. Exp. Allergy200030201208 KlintbergBBerglungNLilgaGWickmanMvan Hage-HamstenMFewer allergic respiratory disorders among farmers’ children in a closed birth cohort from SwedenEur. Respir. J20011711511157 ErnstPCormierYRelative scarcity of asthma and atopy among rural adolescents raised on a farmAm. J. Respir. Crit. Care Med200016115631566 RemesSIivanainenKKoskelaHPekkanenJWhich factors explain the lower prevalence of atopy amongst farmers’ children?Clin. Exp. Allergy200333427434 LeynaertBNeukirchCJarvisDChinnSBurneyPNeukirchFon behalf of the European Community Respiratory Health SurveyDoes living on a farm during childhood protect against asthma, allergic rhinitis, and atopy in adulthood?Am. J. Respir. Crit. Care Med200116418291834 Gassner-BachmannMWüthrichBFarmers’ children suffer less from hay fever and asthmaDtsch. Med. Wochenschr2000125924931 VercelliDAdvances in asthma and allergy genetics in 2007J. Allergy Clin. Immunol2008122267271 GodfreyRAsthma and IgE levels in rural and urban communities of The GambiaClin. Allergy19755201207 BråbäckLDoes farming provide protection from asthma and allergies?Acta Paediatr20029111471149 BachBMølhaveLIndeklimasyndromet: the sick building syndromeUgeskr. Laeg198714910121017 Population and Public Health Branch (PPHB), Health CanadaFarmers at lower risks for many diseasesFarm Family Health1995313 BlairASandlerDTaroneRLubinJThomasKHoppinJSamanicCCobleJKamelFKnottCDosemeciMZahmSLynchCRothmanNAlavanjaMMortality among participants in the agricultural health studyAnn. Epidemiol200515279285 RoncoGCostaGLyngeECancer risk among Danish and Italian farmersBr. J. Ind. Med199249220225 SchoemakerMSwerdlowAHepworthSvan TongerenMMuirKMcKinneyPHistory of allergies and risk of glioma in adultsInt. J. Cancer200611921652172 GoedertJCotéTVirgoPScoppaSKingmaDGailMJaffeEBiggarRfor the AIDS-Cancer Match Study GroupSpectrum of AIDS-associated malignant disordersLancet199835118331839 FrischMBiggerREngelsEGoedertJfor the AIDS-Cancer Match Registry Study GroupAssociation of cancer with AIDS-related immunosuppression in adultsJAMA200128517361745 GrulichAWanXLawMCoatesMKaldorJRisk of cancer in people with AIDSAIDS199913839843 SchiffDGliomas following organ transplantation: analysis of the contents of a tumor registryJ. Neurosurg2004101932934 NaumovaEMystery of seasonality: getting the rhythm of natureJ. Public Health Policy200627212 AndersonJSeasonality of symptomatic bacterial urinary infections in womenJ. Epidemiol. Community Health198337286290 NagashimaKYasuiKKimuraJWashizuMYamaguchiKMoriWInduction of brain tumors by a newly isolated JC virus (Tokyo-1 strain)Am. J. Pathol1984116455463 Zu RheinGVarakisJPerinatal induction of medulloblastomas in Syrian golden hamsters by a human polyoma virus (JC)Natl. Cancer Inst. Monogr197951205208 LondonWHouffAMaddenDFuccilloDGravellMWallenWPalmerASeverJPadgettBWalkerDZuRheinGOhashiTBrain tumors in owl monkeys inoculated with a human polyomavirus (JC virus)Science197820112461249 LondonWHouffSMcKeeverPWallenWSeverJPadgettBWalkerDViral induced astrocytomas in squirrel monkeysProg. Clin. Biol. Res1983105227237 RollisonDHelzlsouerKAlbergAHoffmanSHouJDanielRShahKMajorESerum antibodies to JC virus, BK virus, simian 40 virus, and the risk of incident adult astrocytic brain tumorsCancer Epidemiol. Biomarkers Prev200312460463 ZimmermanHThe significance of experimental gliomas for human diseaseGliomas Current Concepts in Biology, Diagnosis, and TherapyHekmatpanahJSpringer-VerlagNew York, NY, USA1975619 SchumanLChoiNGullenWRelationship of central nervous system neoplasms to Toxoplasma gondii infectionAm. J. Public Health Nations Health196757848856 WrenschMWeinbergAWienckeJMiikeRSisonJWiemelsJBargerGDeLorenzeGAldapeKKelseyKHistory of chickenpox and shingles and prevalence of antibodies to varicella-zoster virus and three other herpesviruses among adults with glioma and controlsAm. J. Epidemiol2005161929938 WrenschMWeinbergAWienckeJMiikeRBargerGKelseyKPrevalence of antibodies to four herpesviruses among adults with glioma and controlsAm. J. Epidemiol2001154161165 BithellJDraperGGorbachPAssociation between malignant disease in children and maternal virus infectionsBr. Med. J197324706708 DickinsonHNyariTParkerLChildhood solid tumours in relation to infections in the community in Cumbria during pregnancy and around the time of birthBr. J. Cancer200287746750 LinosAKardaraMKosmidisHKatriouDHatzisCKontzoglouMKoumandakisETzartzatou-StathopoulouFReported influenza in pregnancy and childhood tumourEur. J. Epidemiol199814471475 FearNRomanEAnsellPBullDMalignant neoplasms of the brain during childhood: the role of prenatal and neonatal factors (United Kindom)Cancer Causes Control200112443449 LinetMGridleyGCnattingiusSNicholsonHMartinssonUGlimeliusBAdamiHZackMMaternal and perinatal risk factors for childhood brain tumors (Sweden)Cancer Causes Control19967437448 KaiserLCouchRGalassoGGlezenWWebsterRWrightPHaydenFFirst International Symposium on Influenza and Other Respiratory Viruses: summary and overview: Kapalua, Maui, Hawaii, December 4–6, 1998Antiviral Res199942149175 MelnikovONikolskyIDugovskayaLBalitskayaNKravchukGSeasonal aspects of immunological reactivity of human and animal organismJ. Hyg. Epidemiol. Microbiol. Immunol198731225230 CarandenteFAngeliADe VechiADammaccoFHalbergFMultifrequency rhythms of immunologic functionsChronobiologia198815723 KoPEylesDBurneTMackay-SimAMcGrathJSeason of birth and risk of brain tumors in adultsNeurology2005641317 HillmanLHaddadJPerinatal vitamin D metabolism. III. Factors influencing late gestational human serum 25-hydroxyvitamin DAm. J. Obstet. Gynecol1976125196200 VerityCBurmanDBeadlePHoltonJMorrisASeasonal changes in perinatal vitamin D metabolism maternal and cord blood biochemistry in normal pregnanciesArch. Dis. Child198156943948 HolickMSunlight and vitamin D for bone and prevention of autoimmune diseases, cancers, and cardiovascular diseasesAm. J. Clin. Nutr2004801678S1688S ChatfieldSBrandCEbelingPRussellDVitamin D deficiency in general medical inpatients in summer and winterInter. Med. J200737377382 LevisSGomezAJimenezCVerasLMaFLaiSHollisBRoosBVitamin D deficiency and seasonal variation in an adult South Florida populationJ. Clin. Endocrinol. Metab20059015571562 EylesDBrownJMackay-SimAMcGrathJFeronFVitamin D3 and brain developmentNeuroscience2003118641653 GiovannucciEExpanding roles of vitamin DJ. Clin. Endocrinol. Metab200994418420 HolickMVitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosisAm. J. Clin. Nutr200479362371 KrickerAArmstrongBDoes sunlight have a beneficial influence on certain cancers?Prog. Biophys. Mol. Biol200692132139 GiovannucciEThe epidemiology of vitamin D and cancer incidence and mortality: a review (United States)Cancer Causes Control2005168395 McGrathJKeepingDSahaSChantDLiebermanDO’CallaghanMSeasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape?Early Hum. Dev200581609618 BarkerDMaternal nutrition, fetal nutrition, and disease in later lifeNutrition199713807813 BarkerDThe developmental origins of adult diseaseJ. Am. Coll. Nutr200423588S595S BogovskiPBogovskiSAnimal species in which N-nitroso compounds induce cancerInt. J. Cancer198127471474 KoestnerADenlingerRInduction of neurogenic and lymphoid neoplasms by the feeding of threshold levels of methyl- and ethylnitrosourea precursors to adult ratsFood Cosmet. Toxicol197513605609 BerleurMCordierSThe role of chemical, physical, or viral exposures and health factors in neurocarcinogenesis: Implications for epidemiologic studies of brain tumorsCancer Causes Control19956240256 BoeingHSchlehoferBBlettnerMWahrendorfJDietary carcinogens and the risk for glioma and meningioma in GermanyInt. J. Cancer199353561565 LeeMWrenschMMiikeRDietary and tobacco factors for adult onset glioma in the San Francisco Area (California, USA)Cancer Causes Control199781324 RollisonDHelzlsouerKProcessed meat consumption and gliomas in a Maryland cohortCancer Causes Control20041599100 BlowersLPreston-MartinSMackWDietary and other lifestyle factors of women with brain gliomas in Los Angeles County (California, USA)Cancer Causes Control19978512 FraserPChilversCFoxJRisk assessment of N-nitroso compounds for human health: Human relevance, epidemiology and occupational exposureOncology198037278281 TerryMHoweGPogodaJZhangFAhlbomAChoiWGilesGLittleJLubinFMénégozFRyanPSchlehoferBPreston-MartinSAn international case-control study of adult diet and brain tumor risk: a histology-specific analysis by food groupAnn. Epidemiol200919161171 van Hanswijck de JongeLWallerGStettlerNEthnicity modifies seasonal variation in birth weight and weight gain of infantsJ. Nutr200313314151418 BucklesKHungermanDSeason of birth and later outcomes: old questions, new answersNational Bureau of Economic ResearchCambridge, MA, USA2008; Available online: http://www.nber.org/papers/w14573 (accessed on 08 April 2010). ChodickGShalevVGorenIInskipPSeasonality in birth weight in Israel: new evidence suggests several global patterns and different etiologiesAnn. Epidemiol200717440446 CurhanGWillettWRimmESpiegelmanDAscherioAStampferMBirth weight and adult hypertension, diabetes mellitus and obesity in US menCirculation19969432463250 BensonVPirieKGreenJCasabonneDBeralVMillion Women Study Collaborators. Lifestyle factors and primary glioma and meningioma tumours in the Million Women Study cohortBr. J. Cancer200899185190 HarderTPlagemannAHarderABirth weight and subsequent risk of childhood primary brain tumors: a meta-analysisAm. J. Epidemiol2008168366373 FallisGHilditchJA comparison of seasonal variation in birthweights between rural Zaire and OntarioCan. J. Public Health198980205208 PowlsABottingNCookeRMarlowNHandedness in very-low-birthweight (VLBW) children at 12 years of age: relation to perinatal and outcome variablesDev. Med. Child Neurol199638594602 SaigalSRosenbaumPSzatmariPHoultLNon-right handedness among ELBW and term children at eight years in relation to cognitive function and school performanceDev. Med. Child Neurol199234425433 MartinMJonesGHandedness and season of birth: a gender-invariant relationCortex199935123128 InskipPTaroneRBrennerAFineHBlackPShapiroWSelkerRLinetMHandedness and risk of brain tumors in adultsCancer Epidemiol. Biomarkers Prev200312223225 HepperPShahidullahSWhiteRHandedness in the human fetusNeuropsychologia19912911071111 GeschwindNGalaburdaACerebral Lateralization: Biological Mechanisms, Associations, and Pathology: I. A hypothesis and a program for researchArch. Neurol198542428459 GeschwindNGalaburdaACerebral Lateralization: Biological Mechanisms, Associations, and Pathology: II. A hypothesis and a program for researchArch. Neurol198542521552 GeschwindNGalaburdaACerebral Lateralization: Biological Mechanisms, Associations, and Pathology: III. A hypothesis and a program for researchArch. Neurol198542634654 WitelsonSNeural sexual mosaicism: sexual differentiation of the human temporo-parietal region for functional asymmetryPsychoneuroendocrinology199116131153 GeschwindNBehanPLeft-handedness: an association with immune disease, migraine, and developmental learning disorderProc. Natl. Acad. Sci. U.S.A19827950975100 BrydenMMcmanusIBulman-FlemingMEvaluating the empirical support for the Geschwing-Behan-Galaburda model of cerebral lateralizationBrain Cogn199426103167 BrydenPBruynJFletcherPHandedness and health: an examination of the association between different handedness classifications and health disordersLaterality200510429440 FritschiLDivitiniMTalbot-SmithAKnuimanMLeft-handedness and risk of breast cancerBr. J. Cancer200797686687 RamadhaniMEliasSvan NoordPGrobbeeDPeetersPUiterwaalCInnate left handedness and risk of breast cancer: case-cohort studyBMJ2005331882883 Titus-ErnstoffLNewcombPEganKBaronJGreenbergETrichopoulosDWillettWStampferMLeft-handedness in relation to breast cancer risk in postmenopausal womenEpidemiology200011181184 TrichopoulosPIs breast cancer initiated in utero?Epidemiology199019596 NichollsMSeasonal trends in the birth of sinistralsLaterality19983241253 RonkainenHPakarinenAKirkinenPKauppilaAPhysical exercise-induced changes and season-associated differences in the pituitary-ovarian function of runners and joggersJ. Clin. Endocrinol. Metab198560416422 MartikainenHRuokonenATomásCKauppilaASeasonal changes in pituitary function: amplification of midfollicular luteinizing hormone secretion during the dark seasonFertil. Steril199665718720 TestartJFrydmanRRogerMSeason influence of diurnal rhythms in the onset of the plasma luteinizing hormone surge in womenJ. Clin. Endocrinol. Metab198255374377 ScheirsJVingerhoetsAHandedness and other laterality indices in women prenatally exposed to DESJ. Clin. Exp. Neuropsychol199517725730 SchachterSHandedness in women with intrauterine exposure to diethylstilberstrolNeuropsychologia199432619623 NassRBakerSSpeiserPVirdisRBalsamoACacciariELocheADumicMNewMHormones and handedness: left-hand bias in female congenital adrenal hyperplasia patientsNeurology198737711715 StuerenburgHBreivikIPuchnerMLohmannFKunzeKTestosterone is locally metabolized in human brain tumors, with possible qualitative and quantitive changes in its effectsNeuro. Endocrinol. Lett199818203213 FurthJCliftonKExperimental pituitary tumoursThe Pituitart GlandHassisGDonovanBUniversity of California PressBerkeley and Los Angeles, CA, USA1966460497 AvtsynAYablonovskayaLEffects of disturbances in the hormonal status on experimental brain tumorsActa Unio Int. Contra Cancrum19642015191522 CollinsRWhen left-handed mice live in right-handed worldsScience1975187181184 VuoksimaaEKoskenvuoMRoseRKaprioJOrigins of handedness: a nationwide study of 30161 adultsNeuropsychologia20094712941301 MedlandSDuffyDWrightMGeffenGHayDLevyFvan-BeijsterveldtCWillemsenGTownsendGWhiteVHewittAMackeyDBaileyJSlutskeWNyholtDTreloarSMartinNBoomsmaDGenetic influences on handedness: data from 25,732 Australian and Dutch twin familesNeuropsychogia200947330337 DeromCThieryEVlietinckRLoosRDeromRHandedness in twins according to zygosity and chorion type: a preliminary reportBehav. Genet199626407408 McManusIHandedness in twins: a critical reviewNeuropsychologia198018347355 MedlandSWrightMGeffenGHayDLevyFMartinNDuffyDSpecial twin environments, genetic influences and their effects on the handedness of twins and their siblingsTwin Res20036119130 SommerIRamseyNMandlRKahnRLanguage lateralization in monozygotic twin pairs concordant and discordant for handednessBrain200212527102718 CosenzaRMingotiSSeason of birth and handedness revisitedPercept. Mot. Skills199581475480 WardJMillikenGDodsonDStaffordDWallaceMHandedness as a function of sex and age in a large population of LemurJ. Comp. Psychol1990104167173 WellsDMillsoppSLateralized behaviour in the domestic catFelis silvestris catus. Anim. Behav200978537541 WellsDLateralised behaviour in the domestic dogCanis familiaris. Behav. Processes2003612735 HopkinsWBardKHemispheric specialization in infant chimpanzees (Pan troglodytes), evidence for a relation with gender and arousalDev. Psychobiol199326219235 RothmanKGreenlandJModern EpidemiologyLippincott-RavenPhiladelphia, PA, USA1998 HillAThe environment and disease: Association or causation?Proc. R. Soc. Med196558295300 Table

Summary of studies on season of birth and adult glioma risk.

Reference, Year, Country Study design Cases (M=Male, F=Female) Referents Risk estimates and/or p-values Comments
Brenner, et al. 2004 U.S.A [16] Case-referent Low-grade glioma, n = 135.High-grade glioma, n = 354.63% of the low-grade gliomas were oligo-dendrogioma, astrocytoma, or mixed gliomas. 86% of high-grade gliomas were glioblastoma or anaplastic astrocytoma.M/F ratio = 1.3.Mean age = 52yrs. Frequency matched (by hospital, age, sex, race, ethnicity, and distance of residence from hospital), n = 799. Sinusoidal test of periodicity, χ2=6.1 (2df), p = 0.04. Risk peaked in February and troughed in August (OR = 1.5, CI not provided). Incident cases. Hospital-based referents. Adjustment by education, marital status, place of birth, handedness, birth order, and history of allergy or auto immune disease did not change results. Excluding different diagnostic subgroups of referents from the analysis did not materially change the estimated parameters of the periodic function.
Efird 2009 U.S.A. [21] Case-referent Primary intracranial gliomas, n = 797. Frequency matched within state of current residence to cases (2:1 to projected number of cases) by age and sex, n = 1,174. Sinusoidal logistic regression model. All participants, peak day = 169, p = 0.0469. Born “on” farm, peak day = 283, p = 0.1579. Born “off” farm, peak day = 150, p = 0.0049. GBM, peak day = 146, p = 0.1456. Non-GBM, peak day = 187, p = 0.0603. Adjusted for age, sex, and state of residence. Population-based controls. Participants were not asked about handedness.
Houben, et al. 2005 The Netherlands [20] Tumor registry cases to all cancer patients comparison. Pilocytic astrocytoma, n = 37.Other astrocytoma, n = 1,064.Oligodendroglioma, n = 131.Other glioma, n = 234. 59.5% males. Median age = 52yrs.Age range = 0–92yrs. Monthly births adjusted to all cancer patients registered by the cancer registry. Edward’s test for sinusoidal variation, p < 0.05. Hospital-based referent population. Adults analyzed together with children.
Koch, et al. 2006 Germany [17] Tumor registry to population cases comparison. Glioblastoma, n = 299M, 202F. Mean age (±SD) = 57.1 ± 14.2 yrs. Population normalized monthly births Circannual cosinor model, r2 = 0.34, p < 0.05. Maximum frequency of births was found in Jan. Monthly mean birth freq = 127.9 (SEM = 7.1). Analysis not adjusted for age, sex. Did not specify the reference years of the birth rates used for normalization of the observed incidence data.
Mainio, et al. 2006 Finland [18] Surgical record cases to population census comparison. Grade I–II gioma, n = 9M, 10F.Grade III–IV glioma, n = 14M, 8F. Meningioma, n = 7M, 26F.Pituitary adenoma, n = 5M, 3F. Acoustic neurinoma, n = 4M, 3F. Other, n = 0M, 6F. Mean age (±SD), F = 49.4 ± 11.5 yrs,. M = 49.4 ± 11.5 yrs. Monthly births in the general population over the years corresponding to the entire range of year of births of the brain tumor patients (born in the years 1915–1971). Observed to expected ratio = 1.3 (95%CI = 1.01–1.77). Comparison: December–February to March–November. Winter trough of births reported for low-grade glioma (adj. ratio = 0.4, CI not provided). Risk only separately reported for low-grade gliomas. Excluded cases not surgically treated.
Staykov, et al. 2009 Germany [19] Tumor registry cases to population census comparison. Mixed glioma, n = 46M, 32F.Ependymoma, n = 48M, 51F.Other glioma, n = 34M, 17F.Anaplastic astrocytoma, n = 122M, 99F. Pilocytic astrocytoma, 15M, 8F. Other astrocytoma, n = 138M, 97F.Glioblastoma, 805M, 560F.Oligodendroglioma, 52M, 50F.Mean age (±SD), M = 54 ± 14, F = 54 ± 14. Monthly births for the years 1931 to 1986 (except 1944) in the general Bavarian population. Roger-test of seasonality, p = 0.54 F, p = 0.11 M. The estimated peak-trough ratio of glioma in persons born in the month with the greatest number of cases compared to month with lowest number was 1.07 in M (95%CI=1.00–1.25) and 1.16 in F (95%CI=1.00–1.39). Incident cases. Data not analyzed separately by low- and high-grade glioma. The analysis of time trends in the distribution of monthly births adjusted for length of month revealed a pronounced absolute maximum of monthly births in February and March prior to 1965, which has gradually decreased in prominence during the subsequent decades. Analysis not adjusted for handedness, education level, or history of allergy/autoimmune disease.