Background

Individual exposure to ultraviolet radiation (UVR) is challenging to measure, particularly for diseases with substantial latency periods between first exposure and diagnosis of outcome, such as cancer. To guide the choice of surrogates for long-term UVR exposure in epidemiologic studies, we assessed how well stable sun-related individual characteristics and environmental/meteorological factors predicted daily personal UVR exposure measurements.

Methods

We evaluated 123 United States Radiologic Technologists subjects who wore personal UVR dosimeters for 8 hours daily for up to 7 days (N = 837 days). Potential predictors of personal UVR derived from a self-administered questionnaire, and public databases that provided daily estimates of ambient UVR and weather conditions. Factors potentially related to personal UVR exposure were tested individually and in a model including all significant variables.

Results

The strongest predictors of daily personal UVR exposure in the full model were ambient UVR, latitude, daily rainfall, and skin reaction to prolonged sunlight (R2 = 0.30). In a model containing only environmental and meteorological variables, ambient UVR, latitude, and daily rainfall were the strongest predictors of daily personal UVR exposure (R2 = 0.25).

Conclusions

In the absence of feasible measures of individual longitudinal sun exposure history, stable personal characteristics, ambient UVR, and weather parameters may help estimate long-term personal UVR exposure.

Objective

We examined the associations between cigarette smoking, alcohol intake, and thyroid cancer risk in a pooled analysis of five prospective studies.

Methods

Data from five prospective U.S. studies were standardized and then combined into one aggregate dataset (384,433 men and 361,664 women). Pooled hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer were estimated from mutually-adjusted models of cigarette smoking and alcohol intake, which were additionally adjusted for age, sex, education, race, marital status, body mass index, and cohort.

Results

Over follow-up, 1,003 incident thyroid cancer cases (335 men and 668 women) were identified. Compared to never smokers, current smoking was associated with reduced risk of thyroid cancer (HR=0.68, 95% CI:0.55-0.85); this association was slightly stronger among non-drinkers (HR=0.46, 95% CI:0.29-0.74). No reduction in risk was observed for former, compared to never, smokers. Greater smoking intensity, duration, and pack-years were associated with further reductions in risk among former and current smokers. Alcohol intake was also inversely associated with thyroid cancer risk (≥7 drinks/week versus 0, HR=0.72, 95% CI:0.58-0.90, P-trend=0.002). Inverse associations with smoking and alcohol were more pronounced for papillary versus follicular tumors.

Conclusion

The results of this pooled analysis suggest that both cigarette smoking and alcohol consumption are associated with reduced risks of papillary thyroid cancer and, possibly, follicular thyroid cancer.

Analyzing data from over 650,000 individuals, Dr. Steven Moore and colleagues report that greater amounts of leisure-time physical activity were associated with higher life expectancy across a wide range of activity levels and body mass index groups.

Background

Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis.

Methods and Findings

We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21–90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1–3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6–2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3–4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5–24.9) was associated with a gain of 7.2 (95% CI: 6.5–7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report.

Conclusions

More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Regular physical activity is essential for human health. It helps to maintain a healthy body weight and prevents or delays heart disease, type 2 diabetes, and some cancers. It also makes people feel better and increases life expectancy. The World Health Organization (WHO) currently recommends that adults do at least 150 minutes of moderate- to vigorous-intensity physical activity every week. Moderate-intensity physical activities (for example, brisk walking and gardening) require a moderate amount of effort and noticeably increase the heart rate; vigorous-intensity physical activities (for example, running or fast swimming) require a large amount of effort and cause rapid breathing and a substantial heart rate increase. Worryingly, people in both developed and developing countries are becoming increasingly physically inactive. People are sitting at desks all day instead of doing manual labor; they are driving to work in cars instead of walking or cycling; and they are participating in fewer leisure time physical activities.

Why Was This Study Done?

Although various studies suggest that physical activity increases life expectancy, few have quantified the years of life gained at distinct levels of physical activity. Moreover, the difference in life expectancy between active, overweight individuals and inactive, normal weight individuals has not been quantified. Thus, it is hard to develop a simple public health message to maximize the population benefits of physical activity. In this pooled prospective cohort analysis, the researchers determine the association between levels of leisure time physical activities, such as recreational walking, and years of life gained after age 40, both overall and within body mass index (BMI) groups. A pooled prospective cohort analysis analyzes the combined data from multiple studies that have followed groups of people to investigate associations between baseline characteristics and outcomes such as death. BMI is a ratio of weight to height, calculated by dividing a person's weight by their height squared; normal weight is defined as a BMI of 18.5–24.9 kg/m2, obesity (excessive body fat) is defined as a BMI of more than 30 kg/m2.

What Did the Researchers Do and Find?

The researchers pooled self-reported data on leisure time physical activities and BMIs from nearly 650,000 individuals over the age of 40 years enrolled in one Swedish and five US prospective cohort studies, most of which were investigating associations between lifestyle factors and disease risk. They used these and other data to calculate the gain in life expectancy associated with specific levels of physical activity. A physical activity level equivalent to brisk walking for up to 75 minutes per week was associated with a gain of 1.8 years in life expectancy relative to no leisure time activity. Being active—having a physical activity level at or above the WHO-recommended minimum of 150 minutes of brisk walking per week—was associated with an overall gain of life expectancy of 3.4–4.5 years. Gains in life expectancy were seen also for black individuals and former smokers, groups for whom relatively few data had been previously available. The physical activity and life expectancy association was also evident at all BMI levels. Being active and normal weight was associated with a gain of 7.2 years of life compared to being inactive and class II+ obese (having a BMI of more than 35.0 kg/m2). However, being inactive but normal weight was associated with 3.1 fewer years of life compared to being active but class I obese (having a BMI of 30–34.9 kg/m2).

What Do These Findings Mean?

These findings suggest that participation in leisure time physical activity, even below the recommended level, is associated with a reduced risk of mortality compared to participation in no leisure time physical activity. This result may help convince currently inactive people that a modest physical activity program may have health benefits, even if it does not result in weight loss. The findings also suggest that physical activity at recommended levels or higher may increase longevity further, and that a lack of leisure time physical activity may markedly reduce life expectancy when combined with obesity. Although the accuracy and generalizability of these findings may be limited by certain aspects of the study's design (for example, some study participants may have overestimated their leisure time physical activity), these findings reinforce the public health message that both a physically active lifestyle and a normal body weight are important for increasing longevity.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001335.

The World Health Organization provides information about physical activity and health (in several languages); its 2010 Global Recommendations on Physical Activity for Health is available in several languages

The US Centers for Disease Control and Prevention provides information on physical activity for different age groups; its Physical Activity for Everyone webpages include guidelines, instructional videos, and personal success stories

The UK National Health Service information source NHS Choices also explains the benefits of regular physical activity and includes physical activity guidelines, tips for exercising, and some personal stories

MedlinePlus has links to other resources about exercise and physical fitness (in English and Spanish)

In a pooled analysis of 4 US epidemiologic studies (1993–2001), the authors evaluated the role of 5 female reproductive factors in 357 women with glioma and 822 controls. The authors further evaluated the independent association between 5 implicated gene variants and glioma risk among the study population, as well as the joint associations of female reproductive factors (ages at menarche and menopause, menopausal status, use of oral contraceptives, and menopausal hormone therapy) and these gene variants on glioma risk. Risk estimates were calculated as odds ratios and 95% confidence intervals that were adjusted for age, race, and study. Three of the gene variants (rs4295627, a variant of CCDC26; rs4977756, a variant of CDKN2A and CDKN2B; and rs6010620, a variant of RTEL1) were statistically significantly associated with glioma risk in the present population. Compared with women who had an early age at menarche (<12 years of age), those who reported menarche at 12–13 years of age or at 14 years of age or older had a 1.7-fold higher risk and a 1.9-fold higher risk of glioma, respectively (P for trend = 0.009). Postmenopausal women and women who reported ever having used oral contraceptives had a decreased risk of glioma. The authors did not observe joint associations between these reproductive characteristics and the implicated glioma gene variants. These results require replication, but if confirmed, they would suggest that the gene variants that have previously been implicated in the development of glioma are unlikely to act through the same hormonal mechanisms in women.

Background

Autoimmunity is clearly linked with hematologic malignancies, but less is known about autoimmunity and alimentary tract cancer risk, despite the specific targeting of alimentary organs and tissues by several autoimmune diseases. We therefore conducted the first systematic evaluation of a broad range of specific autoimmune diseases and risk for subsequent alimentary tract cancer.

Methods

Based on 4,501,578 U.S. male Veterans, we identified 96,277 men who developed alimentary tract cancer during up to 26.2 years of follow-up. Using Poisson regression methods we calculated relative risks (RR) and 95% confidence intervals.

Results

A history of autoimmune disease with localized alimentary tract effects generally increased cancer risks in the organ(s) affected by the autoimmune disease, such as primary biliary cirrhosis and liver cancer (RR=6.01, 4.76–7.57); pernicious anemia and stomach cancer (RR=3.17, 2.47–4.07); and ulcerative colitis and small intestine, colon, and rectal cancers (RR=2.53, 1.05–6.11; RR=2.06, 1.70–2.48; and RR=2.07, 1.62–2.64, respectively). In addition, a history of celiac disease, reactive arthritis (Reiter’s disease), localized scleroderma, and systemic sclerosis all were associated significantly with increased risk of esophageal cancer (RR=1.86–2.86). Autoimmune diseases without localized alimentary tract effects generally were not associated with alimentary tract cancer risk, with the exception of decreased risk for multiple alimentary tract cancers associated with a history of multiple sclerosis.

Conclusions

Our findings support the importance of localized inflammation in alimentary tract carcinogenesis. Future research is needed to confirm our findings and improve our understanding of underlying mechanisms by which autoimmune diseases contribute to alimentary tract carcinogenesis.

Background

Thyroid cancer incidence has risen dramatically in the U.S. since the early 1980s. Although the prevalence of obesity has doubled during this time period, the relationship between obesity and thyroid cancer is uncertain.

Methods

We examined the association between body mass index (BMI) and thyroid cancer risk in a pooled analysis of five prospective U.S. studies, including 413,979 women and 434,953 men. Proportional hazards models with attained age as the time metric were adjusted for education, race, marital status, smoking, alcohol intake, and (where appropriate) cohort and sex.

Results

Over follow-up (mean=10.3 years), 768 women and 388 men were diagnosed with thyroid cancer. The risk of thyroid cancer was greater with increasing BMI (per 5 kg/m2: hazard ratio [HR] in women, 1.16 [95% confidence interval (CI), 1.08–1.24]; HR in men, 1.21 [95% CI, 0.97–1.49]). There was no significant heterogeneity between studies (both P>0.05). For women and men combined, the HRs for overweight (25.0–29.9 kg/m2) and obesity (≥30 kg/m2) compared to normal-weight (18.5–24.9 kg/m2) were 1.20 (95% CI, 1.04–1.38) and 1.53 (95% CI, 1.31–1.79), respectively. We found no significant effect modification by other factors, and the results did not differ significantly by histologic type. A significant positive association for BMI in young adulthood (ages 18–20) with thyroid cancer risk was also observed (per 5-kg/m2 increase: HR, 1.18 [95% CI, 1.03–1.35]).

Conclusion

BMI was positively associated with thyroid cancer risk in both men and women.

Impact

Our study provides strong evidence that obesity is an independent risk factor for thyroid cancer.

Recent epidemiologic studies have suggested that ultraviolet radiation (UV) may protect against non-Hodgkin lymphoma (NHL), but few, if any, have assessed multiple indicators of ambient and personal UV exposure. Using the U.S. Radiologic Technologists study, we examined the association between NHL and self-reported time outdoors in summer, as well as average year-round and seasonal ambient exposures based on satellite estimates for different age periods, and sun susceptibility in participants who had responded to two questionnaires (1994-1998, 2003-2005) and who were cancer-free as of the earlier questionnaire. Using unconditional logistic regression, we estimated the odds ratio (OR) and 95% confidence intervals for 64,103 participants with 137 NHL cases. Self-reported time outdoors in summer was unrelated to risk. Lower risk was somewhat related to higher average year-round and winter ambient exposure for the period closest in time, and prior to, diagnosis (ages 20-39). Relative to 1.0 for the lowest quartile of average year-round ambient UV, the estimated OR for successively higher quartiles was 0.68 (0.42-1.10); 0.82 (0.52-1.29); and 0.64(0.40-1.03), p-trend = 0.06), for this age period. The lower NHL risk associated with higher year-round average and winter ambient UV provides modest additional support for a protective relationship between UV and NHL.

Purpose

Previous studies have shown increased risks of second malignancies after non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL); however, no earlier investigation has quantified differences in risk of new malignancy by lymphoma subtype.

Patients and Methods

We evaluated second cancer and leukemia risks among 43,145 1-year survivors of CLL/small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL) from 11 Surveillance, Epidemiology, and End Results (SEER) population-based registries during 1992 to 2006.

Results

Among patients without HIV/AIDS–related lymphoma, lung cancer risks were significantly elevated after CLL/SLL and FL but not after DLBCL (standardized incidence ratio [SIR], CLL/SLL = 1.42, FL = 1.28, DLBCL = 1.00; Poisson regression P for difference among subtypes, PDiff = .001). A similar pattern was observed for risk of cutaneous melanoma (SIR: CLL/SLL = 1.92, FL = 1.60, DLBCL = 1.06; PDiff = .004). Acute nonlymphocytic leukemia risks were significantly elevated after FL and DLBCL, particularly among patients receiving initial chemotherapy, but not after CLL/SLL (SIR: CLL/SLL = 1.13, FL = 5.96, DLBCL = 4.96; PDiff < .001). Patients with HIV/AIDS–related lymphoma (n = 932) were predominantly diagnosed with DLBCL and had significantly and substantially elevated risks for second anal cancer (SIR = 120.50) and Kaposi's sarcoma (SIR = 138.90).

Conclusion

Our findings suggest that differing immunologic alterations, treatments (eg, alkylating agent chemotherapy), genetic susceptibilities, and other risk factors (eg, viral infections, tobacco use) among lymphoma subtypes contribute to the patterns of second malignancy risk. Elucidating these patterns may provide etiologic clues to lymphoma as well as to the second malignancies.

Vitamin D has been hypothesized to protect against cancer. We followed 16,819 participants in NHANES III from 1988 through 2006, expanding upon an earlier NHANES III study (1988–2000). Using Cox proportional hazard regression models, we examined risk related to baseline serum 25-hydroxyvitamin D (25(OH)D) for total cancer mortality, in both sexes, and by racial/ethnic groups, as well as for site-specific cancers. Because serum was collected in the south in cooler months and the north in warmer months, we examined associations by collection season (“summer/higher latitude” and “winter/lower latitude”). We identified 884 cancer deaths during 225,212 person-years. Overall cancer mortality risks were unrelated to baseline 25(OH)D status in both season/latitude groups, and in non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. In men, risks were elevated at higher levels (e.g., for ≥100 nmol/L, RR=1.85 (95% CI=1.02–3.35) compared to <37.5 nmol/L). Athough risks were unrelated to 25(OH)D in all women combined, risks significantly decreased with increasing 25(OH)D in the summer/higher latitude group (for ≥100 nmol/L, RR= 0.52 (95% CI=0.25–1.15) compared to <37.5 nmol/L, P-trend=0.03, based on continuous values). We also observed a suggestion of an inverse association with colorectal cancer mortality(P-trend=0.09) and a positive association with lung cancer mortality among males (P-trend=0.03). Our results do not support a the hypothesis that 25(OH)D is associated with reduced cancer mortality. Although cancer mortality in females was inversely associated with 25(OH)D in the summer/higher latitude group, cancer mortality at some sites was increased among men with higher 25(OH)D. These findings argue for caution before increasing 25(OH)D levels to prevent cancer.

The etiology of meningioma, the second-most common type of adult brain tumor in the United States, is largely unknown. Prior studies indicate that history of immune-related conditions may affect the risk of meningioma. To identify genetic markers for meningioma in genes involved with innate immunity, we conducted an exploratory association study of 101 meningioma cases and 330 frequency-matched controls of European ancestry using subjects from a hospital-based study conducted by the National Cancer Institute. We genotyped 1407 “tag” single nucleotide polymorphisms (SNPs) in 148 genetic regions chosen on the basis of an r2> 0.8 and minor allele frequency > 5% in Caucasians in HapMap1. Risk of meningioma was estimated by odds ratios and 95% confidence intervals. Seventeen SNPs distributed across twelve genetic regions (NFKB1 (3), FCER1G (3), CCR6 (2), VCAM1, CD14, TNFRSF18, RAC2, XDH, C1D, TLR1/TLR10/TLR6, NOS1, DEFA5) were associated with risk of meningioma with p<0.01. Although individual SNP tests were not significant after controlling for multiple comparisons, gene region-based tests were statistically significant (p<0.05) for TNFRSF18, NFKB1, FCER1G, CD14, C1D, CCR6, and VCAM1. Our results indicate that common genetic polymorphisms in innate immunity genes may be associated with risk of meningioma. Given the small sample size, replication of these results in a larger study of meningioma is needed.

Objective

To investigate whether the positive association of body mass index (BMI, kg/m2) with risk of pancreatic cancer is modified by age, sex, smoking status, physical activity, and history of diabetes.

Methods

In a pooled analysis of primary data of seven prospective cohorts including 458,070 men and 485,689 women, we identified 2,454 patients with incident pancreatic cancer during an average 6.9 years of follow-up. Cox proportional hazard regression models were used in data analysis.

Results

In a random-effects meta-analysis, for every 5 kg/m2 increment in BMI, the summary relative risk (RR) was 1.06 (95% confidence interval (CI) 0.99–1.13) for men and 1.12 (95% CI 1.05–1.19) for women. The aggregate analysis showed that compared with normal weight (BMI: 18.5 to <25), the adjusted RR was 1.13 (95% CI 1.03–1.23) for overweight (BMI: 25 to <30) and 1.19 (95% CI 1.05–1.35) for obesity class I (BMI: 30 to <35). Tests of interactions of BMI effects by other risk factors were not statistically significant. Every 5 kg/m2 increment in BMI was associated with an increased risk of pancreatic cancer among never and former smokers, but not among current smokers (P-interaction = 0.08).

Conclusion

The present evidence suggests that a high BMI is an independent risk factor of pancreatic cancer.

BACKGROUND

A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain.

METHODS

We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58).

RESULTS

The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up.

CONCLUSIONS

In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

Objective

Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk.

Methods

We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose–response across genotypes.

Results

There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2–12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0–3.8) and EOR/Gy < 0 (95%CI < 0–14.8) for the GC and CC genotypes, respectively, (pinteraction = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined.

Conclusions

This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.

Burkitt lymphoma (BL) is a unique B-cell non-Hodgkin lymphoma with three established clinical-epidemiological variants: endemic, sporadic, and AIDS-related BL shows characteristic dysregulation of MYC gene, but the causes of MYC dysregulation or BL arising at different ages are poorly understood. Therefore, we examined population-based BL incidence patterns in the United States to determine age-related risk. BL case and population data were obtained from the NCI’s Surveillance, Epidemiology, and End Results Databases (1973–2005). Standard cross-sectional, age-standardized, and age-specific incidence rates were stratified by sex and race and supplemented with age-period-cohort (APC) models. We analyzed 3058 BL cases diagnosed during 1,160,300,297 person-years of observation. Age-standardized incidence rates rose 6.8% per year (95% CI 4.5–9.1) for males and 7.1% (95% CI 3.2–11.1) for females during the study period. The rate among males was 3.2 times that among females, and among Whites 1.3 times that among Blacks. Male-to-female incidence rate ratios did not differ by race, but were 4.2 for pediatric (0–19 years), 4.1 for adult (20–59 years) and 2.0 for geriatric (≥ 60 years) BL. Cross-sectional age-specific rates showed two separate peaks among males and females, near ages 10 and 75 years, and a third peak near age 40 years among males. The tri/bimodal incidence pattern was present in sensitivity analyses excluding registries with many HIV/AIDS cases and in period-specific, cohort-specific analyses. To our knowledge tri/bimodal incidence patterns have not previously been reported for BL. Trimodal/bimodal BL suggests heterogeneity in etiology or biology of BL diagnosed at different ages in males and females.

Studies have examined the associations between cancers and circulating 25-hydroxyvitamin D [25(OH)D], but little is known about the impact of different laboratory practices on 25(OH)D concentrations. We examined the potential impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25(OH)D concentrations. Blood samples from 20 healthy volunteers underwent alternative laboratory procedures: four centrifuging times (2, 24, 72, and 96 h after blood draw); three types of collection tubes (red top serum tube, two different plasma anticoagulant tubes containing heparin or EDTA); and two types of assays (DiaSorin radioimmunoassay [RIA] and chemiluminescence immunoassay [CLIA/LIAISON®]). Log-transformed 25(OH)D concentrations were analyzed using the generalized estimating equations (GEE) linear regression models. We found no difference in 25(OH)D concentrations by centrifuging times or type of assay. There was some indication of a difference in 25(OH)D concentrations by tube type in CLIA/LIAISON®-assayed samples, with concentrations in heparinized plasma (geometric mean, 16.1 ng ml−1) higher than those in serum (geometric mean, 15.3 ng ml−1) (p = 0.01), but the difference was significant only after substantial centrifuging delays (96 h). Our study suggests no necessity for requiring immediate processing of blood samples after collection or for the choice of a tube type or assay.

Objective To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days).

Design Case-control study.

Setting England and Wales.

Participants 2690 childhood cancer cases and 4858 age, sex, and region matched controls from the United Kingdom Childhood Cancer Study (UKCCS), born 1976-96.

Main outcome measures Risk of all childhood cancer, leukaemia, lymphoma, and central nervous system tumours, measured by odds ratios.

Results Logistic regression models conditioned on matching factors, with adjustment for maternal age and child’s birth weight, showed no evidence of increased risk of childhood cancer with in utero exposure to ultrasound scans. Some indication existed of a slight increase in risk after in utero exposure to x rays for all cancers (odds ratio 1.l4, 95% confidence interval 0.90 to 1.45) and leukaemia (1.36, 0.91 to 2.02), but this was not statistically significant. Exposure to diagnostic x rays in early infancy (0-100 days) was associated with small, non-significant excess risks for all cancers and leukaemia, as well as increased risk of lymphoma (odds ratio 5.14, 1.27 to 20.78) on the basis of small numbers.

Conclusions Although the results for lymphoma need to be replicated, all of the findings indicate possible risks of cancer from radiation at doses lower than those associated with commonly used procedures such as computed tomography scans, suggesting the need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages.

As genome-wide association studies of breast cancer are replicating findings and refinement studies are narrowing the signal location, additional efforts are necessary to elucidate the underlying functional relationships. One approach is to evaluate variation in risk by genotype based on known breast carcinogens, such as ionizing radiation. Given the public health concerns associated with recent increases in medical radiation exposure, this approach may also identify potentially susceptible sub-populations. We examined interaction between 27 newly identified breast cancer risk alleles (identified within the NCI Cancer Genetic Markers of Susceptibility and the Breast Cancer Association Consortium genome-wide association studies) and occupational and medical diagnostic radiation exposure among 859 cases and 1083 controls nested within the United States Radiologic Technologists cohort. We did not find significant variation in the radiation-related breast cancer risk for the variant in RAD51L1 (rs10483813) on 14q24.1 as we had hypothesized. In exploratory analyses, we found that the radiation-associated breast cancer risk varied significantly by linked markers in 5p12 (rs930395, rs10941679, rs2067980, and rs4415084) in the mitochondrial ribosomal protein S30 (MRPS30) gene (pinteraction=0.04). Chance, however, may explain these findings, and as such, these results need to be confirmed in other populations with low to moderate levels of radiation exposure. Even though a complete understanding by which these variants may increase breast cancer risk remains elusive, this approach may yield clues for further investigation.

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF –308G>A (rs1800629), lymphotoxin-α (LTA) 252A>G (rs909253), IL10 –3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for “new” participant TNF –308A carriers (NHL: per-allele odds ratio (ORallelic) = 1.10, Ptrend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, Ptrend = 0.004). In the combined population, odds ratios were increased for TNF –308A carriers (NHL: ORallelic = 1.13, Ptrend = 0.0001; DLBCL: ORallelic = 1.25, Ptrend = 3.7 × 10−6; marginal zone lymphoma: ORallelic = 1.35, Ptrend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, Ptrend = 0.006; mycosis fungoides: ORallelic = 1.44, Ptrend = 0.015). The LTA 252A>G/TNF –308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 × 10−8). Results suggested associations between IL10 –3575T>A and DLBCL (Ptrend = 0.02) and IL10 –1082A>G and mantle cell lymphoma (Ptrend = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF –308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.

The incidence of thyroid cancer has been rapidly increasing in the United States, but few risk factors have been established. The authors prospectively examined the associations of self-reported medical history, anthropometric factors, and behavioral factors with thyroid cancer risk among 90,713 US radiologic technologists (69,506 women and 21,207 men) followed from 1983 through 2006. Incident thyroid cancers in 242 women and 40 men were reported. Elevated risks were observed for women with benign thyroid conditions (hazard ratio (HR) = 2.35, 95% confidence interval (CI): 1.73, 3.20), benign breast disease (HR = 1.56, 95% CI: 1.08, 2.26), asthma (HR = 1.68, 95% CI: 1.00, 2.83), and body mass index ≥35.0 versus 18.5–24.9 kg/m2 (HR = 1.74, 95% CI: 1.03, 2.94; P-trend = 0.04). Current smoking was inversely associated with thyroid cancer risk (HR = 0.54). No clear associations emerged for reproductive factors, other medical conditions, alcohol intake, or physical activity. Despite few thyroid cancers in men, men with benign thyroid conditions had a significantly increased risk of thyroid cancer (HR = 4.65, 95% CI: 1.62, 13.34), and results for other risk factors were similar to those for women. Consistent with prior studies, obesity and benign thyroid conditions increased and current smoking decreased the risk of thyroid cancer. The novel findings for benign breast disease and asthma warrant further investigation.

Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case–control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (ORCT/TT = 3.5; 95% confidence interval: 1.8–6.9; Ptrend .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (Ptrend .01); MUTYH rs3219466 (Ptrend .02), and PCNA rs25406 (Ptrend .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (Ptrend .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (Ptrend .03) and ERCC5 rs17655 (Ptrend .05) variants and decreased for the PARP1 rs1136410 (Ptrend .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (Ptrend .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma.

Introduction

Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium.

Methods

We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects.

Results

These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar.

Conclusions

The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.

Ionizing radiation-associated breast cancer risk appears to be modified by timing of reproductive events such as age at radiation exposure, parity, age at first live birth, and age at menopause. However, potential breast cancer risk modification of low- to moderate radiation dose by polymorphic estrogen metabolism-related gene variants has not been routinely investigated. We assessed breast cancer risk of 12 candidate variants in 12 genes involved in steroid metabolism, catabolism, binding, or receptor functions in a study of 859 cases and 1083 controls within the US Radiologic Technologists (USRT) cohort. Using cumulative breast dose estimates from a detailed assessment of occupational and personal diagnostic ionizing radiation exposure, we investigated the joint effects of genotype on the risk of breast cancer. In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the CYP3A4 M445T minor allele (rs4986910, OR=0.3; 95% CI 0.1–0.9). We found a borderline increased breast cancer risk with having both minor alleles of CYP1B1 V432L (rs1056836, CC vs. GG, OR=1.2; 95% CI 0.9–1.6). Assuming a recessive model, the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic x-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose (pinteraction=0.03) and had a similar joint effect for cumulative occupational radiation dose adjusted for personal diagnostic x-ray exposure (pinteraction=0.06). We found suggestive evidence that common variants in selected estrogen metabolizing genes may modify the association between ionizing radiation exposure and breast cancer risk.

Background

The risk factors and co-factors for sporadic childhood BL are unknown. We investigated demographic and age-specific characteristics of childhood BL (0–14 years) in the U.S.

Procedure

BL age-standardized incidence rates (2000 U.S. standard population), were calculated using data obtained from 12 registries in the NCI’s Surveillance, Epidemiology, and End Results program for cases diagnosed from 1992 through 2005. Incidence rate ratios and 95% confidence intervals (95% CI) were calculated by gender, age-group, race, ethnicity, calendar-year period, and registry.

Results

Of 296 cases identified, 56% were diagnosed in lymph nodes, 21% in abdominal organs, not including retroperitoneal lymph nodes, 14% were Burkitt cell leukemia, and 9% on face/head structures. The male-to-female case ratio was highest for facial/head tumors (25:1) and lowest for Burkitt cell leukemia (1.6:1). BL incidence rate was 2.5 (95% CI 2.3–2.8) cases per million person-years and was higher among boys than girls (3.9 vs. 1.1, p<0.001) and higher among Whites and Asians/Pacific Islanders than among Blacks (2.8 and 2.9 vs.1.2, respectively, p<0.001). By ethnicity, BL incidence was higher among non-Hispanic Whites than Hispanic Whites (3.2 vs. 2.0, p=0.002). Age-specific incidence rate for BL peaked by age 3–5 years (3.4 cases per million), then stabilized or declined with increasing age, but it did not vary with calendar-year or registry area.

Conclusions

Our results indicate that early childhood exposures, male-sex, and White race may be risk factors for sporadic childhood BL in the United States.