Alina V. Brenner

History of allergies and autoimmune diseases and risk of brain tumors in adults

To explore a possible influence of the immune system in the development of brain tumors, we evaluated the relationship between history of allergies and autoimmune diseases and risk of brain tumors within a large, hospital‐based case‐control study. Cases (n = 782) were patients recently diagnosed with glioma (n = 489), meningioma (n = 197) or acoustic neuroma (n = 96) at hospitals in Boston, Phoenix and Pittsburgh (USA). Controls (n =799) were patients hospitalized for a variety of nonmalignant conditions and frequency‐matched to cases by hospital, age, sex, race/ethnicity and distance of residence from hospital. Research nurses collected data by personal interview of patients. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. There was a significant inverse association between glioma and history of any allergies (OR = 0.67, 95% CI = 0.52–0.86) or autoimmune diseases (OR = 0.49, 95% CI = 0.35–0.69). No significant associations were evident for meningioma or acoustic neuroma with history of any allergies. An inverse association was observed between meningioma and history of autoimmune diseases (OR = 0.59, 95% CI = 0.38–0.92). There was a suggestion of interaction between allergies and autoimmune diseases on risk of glioma (p = 0.06), with subjects having both conditions being at lowest risk (OR = 0.24, 95% CI = 0.14–0.42). Among the specific conditions, asthma and diabetes showed the most consistent associations (OR = 0.63, 95% CI = 0.43–0.92 and OR = 0.44, 95% CI = 0.27–0.70, respectively). Our results add to evidence that persons with allergies or autoimmune diseases are at reduced risk of glioma. The basis of the associations is not clear, but they might imply a role of immunologic factors in the development of brain tumors. Published 2002 Wiley‐Liss, Inc.

The Increase in Thyroid Cancer Incidence During the Last Four Decades Is Accompanied by a High Frequency of BRAF Mutations and a Sharp Increase in RAS Mutations

CONTEXT Thyroid cancer incidence rates in the United States and globally have increased steadily over the last 40 years, primarily due to a tripling of the incidence of papillary thyroid carcinoma (PTC). OBJECTIVE The purpose of this study was to analyze trends in demographic, clinical, pathologic, and molecular characteristics of PTC from 1974 to 2009. DESIGN AND SETTING We identified and histologically reviewed 469 consecutive cases of PTC from one US institution from 4 preselected periods (1974 to 1985, 1990 to 1992, 2000, and 2009) and assessed BRAF and RAS point mutations and RET/PTC rearrangements among 341 tumors ≥0.3 cm in size. Changes over time were analyzed using polytomous and binary logistic regression; all analyses were adjusted for age and sex. RESULTS During this period, the median age of patients at diagnosis increased from 37 to 53 years (P < .001) and the percentage of microcarcinomas (≤1.0 cm) increased from 33% to 51% (P < .001), whereas extrathyroidal extension and advanced tumor stage decreased from 40% to 21% (P = .005) and from 43% to 28% (P = .036), respectively. Changes in tumor histopathology showed a decrease in classic PTC and an increase in the follicular variant (P < .001). The proportion of tumors with a BRAF mutation was stable (∼46%) but increased from 50% to 77% (P = .008) within classic papillary PTCs. The proportion of tumors with RAS mutations increased from 3% to 25% and within follicular pattern tumors from 18% to 44% (P < .001). The proportion of RET/PTC rearrangements decreased from 11% to 2% (P = .038). CONCLUSIONS Similar to US national trends, we found an increasing age at diagnosis and greater detection of smaller-sized intrathyroidal PTCs. However, the overall proportion of BRAF mutations remained stable. Sharply rising percentages of the follicular variant histology and RAS mutations after 2000 suggest new and more recent etiologic factors. The increased incidence is not likely to be due to environmental or therapeutic radiation because the percentage of RET/PTC rearrangements decreased.

I-131 dose response for incident thyroid cancers in Ukraine related to the Chornobyl accident.

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case–control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose–response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose–response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43–6.34], and the EAR per 104 PY/Gy was 2.21 (95% CI, 0.04–5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. Conclusions: I-131–related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.

Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident

Background:Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose–response are poorly understood.Methods:We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated 131I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear–exponential functions.Results:For thyroid doses <5 Gy, the dose–response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81–5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases.Conclusion:10–15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation.

Cooking oil fumes and risk of lung cancer in women in rural Gansu, China.

Cooking oil fumes have been suggested to increase the risk of lung cancer in Chinese women by exposing them to mutagenic substances. We investigated the association between lung cancer and locally made rapeseed and linseed oils in a population-based case-control study in Gansu Province, China. Two hundred and thirty-three incident, female lung cancer cases diagnosed from 1994-98 were identified. A control group of 459 women was selected from census lists and were frequency matched on age and prefecture. Interviewers obtained information on cooking practices and cooking oil use. The odds ratio (OR) for lung cancer associated with ever-use of rapeseed oil, alone or in combination with linseed oil, was 1.67 (95% CI 1.0-2.5), compared to use of linseed oil alone. ORs for stir-frying with either linseed or rapeseed oil 15-29, 30 and > or =31 times per month were 1.96,1.73, and 2.24, respectively (trend, P=0.03), relative to a lower frequency of stir-frying. Lung cancer risks also increased with total number of years cooking (trend, P<0.09). Women exposed to cooking fumes from rapeseed oil appeared to be at increased risk of lung cancer, and there was some evidence that fumes from linseed oil may have also contributed to the risk.

ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer.

In their previous analysis of papillary thyroid carcinomas (PTCs) from an Ukrainian‐American cohort that was exposed to iodine‐131 (131I) from the Chernobyl accident, the authors identified RET/PTC rearrangements and other driver mutations in 60% of tumors.

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics†

Childhood exposure to iodine‐131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited.

Lung cancer and indoor exposure to coal and biomass in rural China.

Incomplete combustion of coal in homes has been linked with lung cancer in China. We report on a lung cancer case-control study in a rural area of China, where many residents live in underground dwellings and burn coal and unprocessed biomass (crop residues, wood, sticks, and twigs) for heating and cooking. We interviewed 846 patients with lung cancer (626 men, 220 women; aged 30 to 75 years) diagnosed between 1994 and 1998, and 1740 population-based controls. The odds ratio for lung cancer associated with coal use compared with that for biomass in the house of longest residence was 1.29 (95% confidence interval, 1.03 to 1.61), adjusted for smoking and socioeconomic status. The risk for lung cancer increased relative to the percentage of time that coal was used over the past 30 years (P = 0.02). Our findings suggest that coal may contribute to the risk of lung cancer in this rural area of China.

Prospective study of body mass index, physical activity and thyroid cancer.

Increased body size and physical inactivity are positively related to risk of several cancers, but only few epidemiologic studies have investigated body‐mass index (BMI) and physical activity in relation to thyroid cancer. We examined the relations of BMI and physical activity to thyroid cancer in a prospective cohort of 484,326 United States men and women, followed from 1995/1996 to 2003. During 3,490,300 person‐years of follow‐up, we documented 352 newly incident cases of thyroid cancer. The multivariate relative risks (RR) of thyroid cancer for BMI values of 18.5–24.9 (reference), 25.0–29.9 and ≥30 kg m−2 were 1.0, 1.27 and 1.39 [95% confidence interval (CI) = 1.05–1.85]. Adiposity predicted papillary thyroid cancers (RR comparing extreme BMI categories = 1.47; 95% CI = 1.03–2.10) and, based on small numbers, suggestively predicted follicular thyroid cancers (RR = 1.49; 95% CI = 0.79–2.82) and anaplastic thyroid cancers (RR = 5.80; 95% CI = 0.99–34.19). No relation with BMI was noted for medullary thyroid cancers (RR = 0.97; 95% CI = 0.27–3.43). The positive relation of BMI to total thyroid cancer was evident for men but not for women. However, the test of interaction (p = 0.463) indicated no statistically significant gender difference. Physical activity was unassociated with thyroid cancer. The RRs of total thyroid cancer for low (reference), intermediate, and high level of physical activity were 1.0, 1.01 and 1.01 (95% CI = 0.76–1.34, p for trend = 0.931), respectively. Our results support an adverse effect of adiposity on risk for developing total and papillary, and possibly follicular thyroid cancers. Based on only 15 cases, adiposity was unrelated to medullary thyroid cancers. Physical activity was unrelated to total thyroid cancer.

Clinical and epidemiologic characteristics of first primary tumors of the central nervous system and related organs among atomic bomb survivors in Hiroshima and Nagasaki, 1958–1995†

Analysis conducted in the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki found a significant dose‐related excess of tumors of the central nervous system (CNS) and the pituitary gland. The objective of the current study was to evaluate clinical and epidemiologic characteristics of first primary tumors of the CNS and the pituitary gland in this cohort and to compare them with characteristics among other populations.