Parental smoking and risk of childhood brain tumors by functional polymorphisms in polycyclic aromatic hydrocarbon metabolism genes.

BACKGROUND: A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals. METHODS: We assessed 9 functional polymorphisms in 6 genes that affect the metabolism of polycyclic aromatic hydrocarbons (PAH) to evaluate potential interactions with parental smoking during pregnancy in a population-based case-control study of childhood brain tumors. Cases (N = 202) were ≤10 years old, diagnosed from 1984-1991 and identified in three Surveillance, Epidemiology, and End Results (SEER) registries in the western U.S. Controls in the same regions (N = 286) were frequency matched by age, sex, and study center. DNA for genotyping was obtained from archived newborn dried blood spots. RESULTS: We found positive interaction odds ratios (ORs) for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P(interaction) = 0.02; 0.10), such that children with the high-risk (greater PAH activation) genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. A dose-response pattern for paternal smoking was observed among children with the EPHX1 H139R high-risk genotype only (OR(no exposure) = 1.0; OR(≤3 hours/day) = 1.32, 95% CI: 0.52-3.34; OR(>3 hours/day )= 3.18, 95% CI: 0.92-11.0; P(trend )= 0.07). CONCLUSION: Parental smoking during pregnancy may be a risk factor for childhood brain tumors among genetically susceptible children who more rapidly activate PAH in tobacco smoke.

Trends in childhood brain tumor incidence, 1973-2009.

In the mid-1980s, there was a rise in incidence rates of childhood brain tumors (CBT) in the United States that appeared to stabilize at a higher rate in the early 1990 s. An updated analysis of the pattern of CBT over the past 2 decades, with commentary on whether the elevated incidence rate has continued, is past due. We used Surveillance, Epidemiology and End Results (SEER) data to examine trends in incidence of CBT from 1973 through 2009. We examined age-adjusted incidence rates (AAIRs) and secular trends for all malignant brain tumors combined (SEER classification) by histologic tumor type and anatomic site. The incidence of CBT remained stable from 1987 to 2009 [annual percent change (APC) = 0.10; 95 % confidence intervals (CI) -0.39 to 0.61] with an AAIR for all CBT of 3.32 (95 % CI 3.22-3.42). The stability of rates in these two decades contrast the change that occurred in the mid-1980s (1983-1986), when the incidence of CBT increased by 53 % (APC = 14.06; 95 % CI 4.05-25.0). From 1983 to 1986, statistically significant rate increases were observed for pilocytic astrocytoma, PNET/medulloblastoma, and mixed glioma. Further, the rate of increase in pilocytic astrocytoma was similar to the rate of decrease for astrocytomas NOS from 1981 to 2009, suggesting a change from a more general to more specific classification. After the increase in rates in the mid-1980s, rates of CBT over the past two decades have stabilized. Changes in incidence rates of subtypes of tumors over this time period reflect changes both in classification of CBT and in diagnostic techniques.

Childhood brain tumors and maternal cured meat consumption in pregnancy: differential effect by glutathione S-transferases.

BACKGROUND: Some epidemiologic studies suggest that maternal consumption of cured meat during pregnancy may increase risk of brain tumors in offspring. We explored whether this possible association was modified by fetal genetic polymorphisms in genes coding for glutathione S-transferases (GSTs) that may inactivate nitroso compounds. METHODS: We assessed six GST variants: GSTM1 null, GSTT1 null, GSTP1(I105V) (rs1695), GSTP1(A114V) (rs1138272), GSTM3*B (3-bp deletion), and GSTM3(A-63C) (rs1332018) within a population-based case-control study with data on maternal prenatal cured meat consumption (202 cases and 286 controls born in California or Washington, 1978-1990). RESULTS: Risk of childhood brain tumor increased with increasing cured meat intake by the mother during pregnancy among children without GSTT1 [OR = 1.29; 95% confidence interval (95% CI), 1.07-1.57 for each increase in the frequency of consumption per week] or with potentially reduced GSTM3 (any -63C allele; OR = 1.14; 95% CI, 1.03-1.26), whereas no increased risk was observed among those with GSTT1 or presumably normal GSTM3 levels (interaction P = 0.01 for each). CONCLUSIONS: Fetal ability to deactivate nitrosoureas may modify the association between childhood brain tumors and maternal prenatal consumption of cured meats. IMPACT: These results support the hypothesis that maternal avoidance during pregnancy of sources of some nitroso compounds or their precursors may reduce risk of brain tumors in some children.

HIV as a risk factor for lung cancer in women: data from the Women's Interagency HIV Study.

PURPOSE: Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS). METHODS: A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III. RESULTS: Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III. CONCLUSION: HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.

Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes.

BACKGROUND: Insecticides that target the nervous system may play a role in the development of childhood brain tumors (CBTs). Constitutive genetic variation affects metabolism of these chemicals. METHODS: We analyzed population-based case-control data to examine whether CBT is associated with the functional genetic polymorphisms PON1C-108T, PON1Q192R, PON1L55M, BCHEA539T, FMO1C-9536A, FMO3E158K, ALDH3A1S134A, and GSTT1 (null). DNA was obtained from newborn screening archives for 201 cases and 285 controls,

Ambient air pollution and brain cancer mortality.

OBJECTIVE: Growing evidence that ultrafine particles in ambient air can cause brain lesions in animals led us to investigate whether particulate components of air pollution may be associated with brain cancer risk in humans. Air pollution has been associated with respiratory disorders and cardiovascular morbidity and mortality, but associations between air pollutants and brain cancer have not been investigated in adults. METHODS: The analyses included 1,284 deaths due to brain cancer from the Cancer Prevention Study-II, an ongoing prospective mortality study of adults in the United States and Puerto Rico conducted by the American Cancer Society. Air pollution data from national databases for metropolitan areas were combined with residential history and vital status data to estimate exposure to particulate and gaseous air pollution. RESULTS: We found no elevated risk for estimated measures of air pollutants, an unanticipated reduction in risk was found between gaseous air pollutants and brain cancer mortality. CONCLUSION: The findings do not provide evidence of increased risk of brain cancer mortality due to air pollutants.

An international case-control study of maternal diet during pregnancy and childhood brain tumor risk: a histology-specific analysis by food group.

PURPOSE: Maternal dietary data from an international collaborative case-control study on childhood brain tumors were used to evaluate associations between histology-specific risk and consumption of specific food groups during pregnancy. METHODS: Nine study centers from seven countries contributed 1218 cases and 2223 controls. Most cases were diagnosed between 1982 and 1992 and ranged in age from 0 to 19 years. Dietary consumption was measured as average grams per day. RESULTS: Foods generally associated with increased risk were cured meats, eggs/dairy, and oil products; foods generally associated with decreased risk were yellow-orange vegetables, fresh fish, and grains. The cured meat association was specific to astrocytomas (odds ratio [OR] range=1.8-2.5 across astrocytoma subtypes for 4th vs. 1st quartile of consumption, p trends

An international case-control study of adult diet and brain tumor risk: a histology-specific analysis by food group.

PURPOSE: Existing studies of diet and adult brain tumors have been limited by small numbers in histology-specific subgroups. Dietary data from an international collaborative case-control study on adult brain tumors were used to evaluate associations between histology-specific risk and consumption of specific food groups. METHODS: The study included 1548 cases diagnosed between 1984 and 1991 and 2486 control subjects from 8 study centers in 6 countries. Of the 1548 cases, 1185 were gliomas, 332 were meningiomas, and 31 were other tumor types. Dietary consumption was measured as average grams per day. RESULTS: We found inverse associations between some vegetable groups and glioma risk, the strongest for yellow-orange vegetables (odds ratio [OR], 0.7, 95% confidence interval [CI], 0.5-0.9 for the 4th vs. 1st quartile of consumption, p for trend<0.001), and the association was limited to specific glioma subtypes. There was no association with cured meat. Non-cured meat was associated with a modest increase in glioma risk (OR, 1.3; 95% CI, 1.0-1.7 for 4th quartile vs. 1st quartile, p for trend=0.01). We also found positive associations between egg, grain, and citrus fruit consumption and glioma but not meningioma risk. CONCLUSIONS: Our study suggests that selected dietary food groups may be associated with adult gliomas and its subtypes but not meningiomas.

Family cancer history and risk of brain tumors in children: results of the SEARCH international brain tumor study.

OBJECTIVE: To examine whether childhood brain tumors (CBTs) are associated with a family history of brain tumors or other cancers in an international case-control study. METHODS: Cancers in children's first- and second-degree relatives were ascertained by interview with parents of 620 children with astroglial tumors, 255 with primitive neuroectodermal tumors, 324 with other CBTs, and 2,218 controls from Australia, Canada, France, Israel, Italy, Spain, and the US. These were used with histories of neurofibromatosis or tuberous sclerosis to exclude in subanalyses children with Li-Fraumeni or other hereditary syndromes predisposing to brain tumors. RESULTS: A first- or second-degree relative of 4% of children with astroglial tumors, 6% with PNET, 5% with other CBTs, and 5% of controls had had a brain tumor. Any potential differences were statistically non-significant, including when focusing on relatives diagnosed in childhood. In the US, where anatomical sites of relatives' other cancers were known, CBT occurrence was not associated with any other specific site. Results were not markedly altered by exclusion of children with hereditary syndromes. CONCLUSION: Consistent with most prior studies using these methods, we observed no strong relationship between CBT occurrence and cancers in family members.

Comparing self-reported disease outcomes, diet, and lifestyles in a national cohort of black and white Seventh-day Adventists.

INTRODUCTION: Few epidemiologic cohort studies on the etiology of chronic disease are powerful enough to distinguish racial and ethnic determinants from socioeconomic determinants of health behaviors and observed disease patterns. The Adventist Health Study-2 (AHS-2), with its large number of respondents and the variation in lifestyles of its target populations, promises to shed light on these issues. This paper focuses on some preliminary baseline analyses of responses from the first group of participants recruited for AHS-2. METHODS: We administered a validated and pilot-tested questionnaire on various lifestyle practices and health outcomes to 56,754 respondents to AHS-2, comprising 14,376 non-Hispanic blacks and 42,378 non-Hispanic whites. We analyzed cross-sectional baseline data adjusted for age and sex and performed logistic regressions to test differences between responses from the two racial groups. RESULTS: In this Seventh-day Adventist (Adventist) cohort, blacks were less likely than whites to be lifelong vegetarians and more likely to be overweight or obese. Exercise levels were lower for blacks than for whites, but blacks were as likely as whites not to currently smoke or drink. Blacks reported higher rates of hypertension and diabetes than did whites but lower rates of high serum cholesterol, myocardial infarction, emphysema, and all cancers. After we eliminated skin cancer from the analysis, the age-adjusted prevalence of cancer remained significantly lower for black than for white women. The prevalence of prostate cancer was 47% higher for black men than for white men. CONCLUSION: The profile of health habits for black Adventists is better than that for blacks nationally. Given the intractable nature of many other contributors to health disparities, including racism, housing segregation, employment discrimination, limited educational opportunity, and poorer health care, the relative advantage for blacks of the Adventist lifestyle may hold promise for helping to close the gap in health status between blacks and whites nationally.

Effects of human immunodeficiency virus on protracted amenorrhea and ovarian dysfunction.

OBJECTIVE: To characterize ovarian failure and prolonged amenorrhea from other causes in women who are both human immunodeficiency virus (HIV) seropositive and seronegative. METHODS: This was a cohort study nested in the Women's Interagency HIV Study, a multicenter U.S. study of HIV infection in women. Prolonged amenorrhea was defined as no vaginal bleeding for at least 1 year. A serum follicle stimulating hormone more than 25 milli-International Units/mL and prolonged amenorrhea were used to define ovarian failure. Logistic regressions, chi2, and t tests were performed to estimate relationships between HIV-infection and cofactors with both ovarian failure and amenorrhea from other causes. RESULTS: Results were available for 1,431 women (1,139 HIV seropositive and 292 seronegative). More than one half of the HIV positive women with prolonged amenorrhea of at least 1 year did not have ovarian failure. When adjusted for age, HIV seropositive women were about three times more likely than seronegative women to have prolonged amenorrhea without ovarian failure. Body mass index, serum albumin, and parity were all negatively associated with ovarian failure in HIV seropositive women. CONCLUSION: HIV serostatus is associated with prolonged amenorrhea. It is difficult to ascertain whether the cause of prolonged amenorrhea is ovarian in HIV-infected women without additional testing. LEVEL OF EVIDENCE: II-2.

Descriptive epidemiology of vestibular schwannomas.

Vestibular schwannomas, commonly termed acoustic neuromas, arise from the vestibular branch of the eighth cranial nerve (acoustic nerve) and are benign, slow-growing brain tumors that negatively impact patient quality of life. They are thought to account for the majority of intracranial nerve sheath tumors. To describe incidence rate patterns and trends of primary nerve sheath tumors of the brain/CNS and the subset of vestibular schwannomas in two population-based incidence registries, data were obtained from 11 Central Brain Tumor Registry of the United States (CBTRUS) collaborating state registries and the Los Angeles County Cancer Surveillance Program (LACCSP) (1975-1998). Average annual incidence rates were tabulated by age, gender, race, year, and region and were age-adjusted to the year 2000 U.S. standard population. Multiplicative Poisson regression models were used to compare trends in primary nerve sheath tumors of the brain/CNS overall and in subgroups, including vestibular schwannomas, controlling for age, gender, race, microscopic confirmation, and region. Joinpoint regression analysis was used to identify any sharp changes in incidence over time. The overall incidence of primary nerve sheath tumors of the brain/CNS was 1.1 per 100,000 person-years (CBTRUS, 1995-1999 and LACCSP, 1995-1998). The incidence of vestibular schwannomas was similar for both data sets: 0.6 per 100,000 person-years (CBTRUS, 1995-1999) and 0.8 per 100,000 person-years (LACCSP, 1995-1998). Moreover, the incidence of primary nerve sheath tumors of the brain/CNS overall (CBTRUS, 1985-1999 and LACCSP, 1975-1998) and of vestibular schwannomas (CBTRUS, 1992-1999 and LACCSP, 1992-1998) increased over time. However, the incidence of benign schwannomas in sites other than the acoustic nerve either decreased (CBTRUS, 1992-1999) or experienced no significant change (LACCSP, 1992-1998). While improvements in diagnosis and reporting may explain some of these trends, further consideration of potential etiologic factors may be warranted.

Maternal medication use and the risk of brain tumors in the offspring: the SEARCH international case-control study.

N-nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R(1)NNO.COR(2)), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (< or =5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring.

A population-based description of glioblastoma multiforme in Los Angeles County, 1974-1999.

BACKGROUND: There have been reports that the incidence rates of brain tumors have increased over the past few decades, but most have considered all brain tumors together. The authors analyzed the pattern of glioblastoma multiforme (GBM) occurrence in Los Angeles County, California to shed light on the incidence and descriptive epidemiology of this type of brain tumor. METHODS: Data were obtained from the Los Angeles County Cancer Surveillance Program. Incidence rates were analyzed by gender, race, age at diagnosis, period of diagnosis (1974-1981, 1982-1988, or 1989-1999), and socioeconomic status (SES). In addition, data were stratified according to anatomic subsite. A multivariate model describing changes in rates by each of these variables was constructed. RESULTS: Age-specific incidence rates (ASIR) rose sharply after age 30 years. The peak ASIR was at age 70-74 years in males and at age 75-79 years in females. The age-adjusted incidence rate (AAIR) of GBM increased from 1974 to 1999 by an estimated 2.4% per year among males and 2.8% per year among females. Overall, males had a 60% increased risk of brain tumors compared with females. Males had a higher incidence of GBM compared with females at each anatomic subsite except the posterior fossa. The largest male:female ratio occurred in the occipital lobes. Non-Latino whites had the highest incidence rates (2.5 per 100,000) followed by Latino whites (1.8 per 100,000), and blacks (1.5 per 100,000). After 1989, compared with the period before magnetic resonance imaging (MRI) was available, there was an increase in GBM incidence rates among those with of higher SES that was most pronounced in females. The incidence of GBM was highest for frontal lobe tumors and for tumors that involved two or more lobes (overlapping tumors), followed by tumors in the temporal and parietal lobes. In the multivariate analysis, year of diagnosis, SES, gender, race (Latino but not black), site, and age at diagnosis all were important predictors of incidence rate. CONCLUSIONS: GBM incidence increased in Los Angeles County over the last 30 years and especially after 1989, suggesting that the introduction of MRI may have contributed to the increase. Individuals older than age 65 years experienced the greatest increase in incidence over time. Older age, male gender, higher SES, and non-Latino white race increased the risk of GBM. Previously unreported incidence rates for GBM among Latino whites were significantly lower than among non-Latino whites but were intermediate between non-Latino whites and blacks.

A review: dietary and endogenously formed N-nitroso compounds and risk of childhood brain tumors.

Maternal dietary exposure to N-nitroso compounds (NOC) or to their precursors during pregnancy has been associated with risk of childhood brain tumors. Cured meat is one source of exposure to dietary NOC and their precursors. Most epidemiological studies that have examined the role of maternal consumption of cured meats during pregnancy have found a significant positive association between maternal intake of cured meat and the risk of childhood brain tumor (CBT). NOC consist of two main groups, N-nitrosamines and N-nitrosamides. The carcinogenicity profiles of NOC suggest that N-nitrosamides rather than N-nitrosamines are the compounds that may be associated with CBT and that they should be investigated more closely in epidemiological studies. We present a review of the chemical and carcinogenic properties of NOC in connection with the findings of case-control studies. This approach may be helpful in determining the essential information that must be collected in future epidemiological studies on CBT.

Prior hospitalization for epilepsy, diabetes, and stroke and subsequent glioma and meningioma risk.

We conducted a case-control study to evaluate the preclinical association between epilepsy, diabetes, and stroke and primary adult brain tumors. We first identified all 1,501 low-grade glioma, 4,587 high-grade glioma (HGG), and 4,193 meningioma cases reported to the Swedish Cancer Registry from 1987 to 1999. Next, controls (137,485) were randomly selected from the continuously updated Swedish Population Registry and matched to cases diagnosed that year on age and sex. Finally, cases and controls were linked to the Swedish Hospital Discharge Registry (1969-1999). We found that > or =8 years before HGG diagnosis (or control reference year) there was an elevated risk of HGG among people discharged with epilepsy [odds ratio (OR), 3.01; 95% confidence interval (95% CI), 1.73-5.22]. Two to 3 years before HGG diagnosis, this risk increased (OR, 5.33; 95% CI, 3.58-7.93) and was especially strong among people ages <55 years (OR, 13.49; 95% CI, 6.99-25.94). During this 2- to 3-year prediagnostic period, we also found an increased risk of HGG among people discharged with meningitis (OR, 3.02; 95% CI, 1.06-8.59) or viral encephalitis (OR, 12.64; 95% CI, 2.24-71.24). Results are similar for glioblastoma multiforme, low-grade glioma, and meningioma. In contrast, risk of HGG among people discharged with diabetes or stroke does not increase until year of brain tumor diagnosis. The occurrence of excess epilepsy > or =8 years before HGG diagnosis suggests a relatively long preclinical phase, but excess diabetes or stroke appear late in HGG development.

Occupational risk factors for low grade and high grade glioma: results from an international case control study of adult brain tumours.

The majority of suspected occupational risk factors for adult brain tumours have yet to be confirmed as etiologically relevant. Within an international case-control study on brain tumours, lifelong occupational histories and information on exposures to specific substances were obtained by direct interviews to further investigate occupational risk factors for glioma. This is one of the largest studies of brain tumours in adults, including 1,178 cases and 1987 population controls from 8 collaborating study centres matched for age, gender and centre. All occupational information, was aggregated into 16 occupational categories. In a pooled analysis, odds ratios (OR), adjusted for education, were estimated separately for men and women and for high-grade glioma (HGG) and low-grade glioma (LGG), focusing especially on 6 categories defined a priori: agricultural, chemical, construction, metal, electrical/electronic and transport. For men, an elevated OR of glioma associated with the category "metal" (OR = 1.24, 95% CI 0.96-1.62) was seen, which appeared to be largely accounted for by LGG (OR = 1.59, 95% CI 1.00-2.52). For the other 5 occupational categories, no elevated risks for glioma were observed. For women the only noteworthy observation for the 6 a priori categories was an inverse association with the "agriculture" category (OR = 0.60, 95% CI 0.36-0.99). Apart from the 6 major categories, women working in food production or food processing (category "food") showed an increased OR of 1.95 (95% CI 1.04-3.68). None of the 20 substance groups was positively associated with glioma risk. Although some other point estimates were elevated, they lacked statistical significance. The results do not provide evidence of a strong association between occupational exposures and glioma development.

Prescription drug use and risk of acute myeloid leukemia by French-American-British subtype: results from a Los Angeles County case-control study.

Chemotherapy is a well-established risk factor for acute myeloid leukemia (AML) but little is known about other prescription drugs and AML risk. We report data from a population-based Los Angeles County study in which 299 matched case-control pairs had complete data on prescription drug use and 88% of cases were subtyped according to the French-American-British (FAB) criteria. Cases were diagnosed between 1987 and 1994. Prescription nonsteroidal anti-inflammatory drug (NSAID) use for at least 4 weeks in the 2 to 10 years before diagnosis was associated with decreased risk (odds ratio = 0.5, 95% confidence interval=0.3, 1.0; p=0.04) with dose-response most evident for FAB subtype M2 (OR = 0.6, CI: 0.1, 2.9 for duration < or =6 months; OR = 0.2, CI: 0.0, 1.6 for >6 months). For subtype M4, ORs increased with increasing duration of benzodiazepine use in the 2 to 10 years before diagnosis (OR = 1.5, CI: 0.3, 9.0 for < or =6 months vs. OR = 5.0, CI: 0.6, 42.8 for >6 months). These results suggest that prescription drugs other than chemotherapy may have FAB subtype-specific effects on AML risk.