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Purpose: Excess body fatness and physical activity independently influence the risk of several types of cancer. However, few studies have examined whether physical activity mitigates the excess risk associated with higher body mass index (BMI)., Methods: We examined the individual and joint associations between BMI (kg/m 2 ) and leisure-time moderate-to-vigorous physical activity (MVPA, MET-hours/week) with the risk of three established excess body fatness-related cancers (breast, colon, and endometrial) among 43,795 postmenopausal women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort (1992/1993-2015). Further exclusions for women without an intact uterus resulted in 31,805 women for endometrial cancer analyses. Multivariable Cox proportional hazards regression was used to calculate hazard ratio (HR) and 95% confidence intervals (CIs) with interaction terms to assess multiplicative interaction. The relative excess risk due to interaction (RERI) was calculated to assess additive interaction., Results: BMI and MVPA were individually associated with breast and endometrial cancer risk, but only BMI was associated with colon cancer risk. In joint analyses, increasing levels of MVPA did not lower the risk of these cancers among obese women. For example, compared to the common referent (BMI 18.5- < 25 kg/m 2 , MVPA > 0- < 7.5 MET-hours/week), BMI ≥ 30 kg/m 2 was associated with a higher risk of breast cancer among women with low MVPA (> 0-< 7.5 MET-hours/week: HR = 1.42, 95% CI: 1.22 - 1.67) and high MVPA (≥ 15 MET-hours/week: HR = 1.53, 95% CI: 1.25 - 1.87; RERI = 0.20, 95% CI: -0.14, 0.54, multiplicative P interaction  = 0.64)., Conclusion: Our results do not support the hypothesis that leisure-time physical activity mitigates the excess risk associated with higher BMI for risk of breast, endometrial, or colon cancer among postmenopausal women.

Background: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk., Methods: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided., Results: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes., Conclusion: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Some evidence suggests the association between body mass index (BMI) and pancreatic cancer risk is weaker among current smokers than among never smokers., Methods: We examined the association between BMI and pancreatic cancer mortality among adults who reported smoking status at enrollment into Cancer Prevention Study-II in 1982, including 420,543 never smokers, 282,244 former cigarette smokers, and 219,885 current cigarette smokers. After excluding the first 3 years of follow-up to reduce reverse causation, we calculated multivariable-adjusted hazard ratios (HR)., Results: During the full follow-up period from 1985 to 2014, 7,904 participants died of pancreatic cancer. The HR per 5 BMI units was lower among current smokers [HR = 1.14; 95% confidence interval (CI), 1.07-1.20] than never smokers (HR = 1.22; 95% CI, 1.17-1.27), although this difference was not statistically significant ( P = 0.06). BMI was significantly less strongly associated with pancreatic cancer mortality among current smokers reporting ≥20 cigarettes/day (HR = 1.10; 95% CI, 1.03-1.18) than among never smokers. During follow-up within 10 years of enrollment, when current smokers at enrollment were the most likely to have still been smoking, BMI was not associated with pancreatic cancer mortality among current smokers (HR = 1.02; 95% CI, 0.90-1.16, P = 0.03 for difference between current and never smokers). BMI HRs were similar among former and never smokers., Conclusions: These results support a weaker association between BMI and pancreatic cancer among current smokers than among never smokers., Impact: In populations with low smoking prevalence, the pancreatic cancer burden due to BMI is likely to be higher than that predicted by risk estimates from studies including substantial numbers of smokers., (©2020 American Association for Cancer Research.)

Background: Height and weight are commonly used metrics in epidemiologic studies to calculate body mass index. Large cohort studies generally assess height and weight by self-report rather than by measurement. The aim of this study was to assess the validity of self-reported height and weight in the Cancer Prevention Study-3 (CPS-3), a large, nationwide cohort recruited by the American Cancer Society between 2006-2013., Methods: In a subset of CPS-3 participants (n = 2,643), weight and height were assessed at the same time via self-report and in-person measurement. BMI was calculated and classified underweight (<18.5 kg/m2), normal (18.5-<25 kg/m2), overweight (25-<30 kg/m2), or obese (≥30 kg/m2). Self-reported and measured height, weight, and BMI were compared using mean differences and Bland-Altman plots and examined by sex, race/ethnicity, education, marital status, age group, and BMI category., Results: Men and women slightly overreported height and underreported weight. BMI calculated from self-reported data was lower than for measured data for men and women. In analyses stratified by race/ethnicity, age, education, and marital status, older women and women with less than a college degree overreported height. Approximately 13% of men and 7% of women were misclassified into a lower self-reported BMI category, with misclassification of BMI being greatest in obese men and women., Conclusions: Overall, height, weight, and BMI were well-reported, and this study further suggests that BMI computed from self-reported weight and height is a valid measure in men and women across different socio-demographic groups., Competing Interests: The authors have declared that no competing interests exist.

Higher body mass index (BMI; weight (kg)/height (m)2) is associated with increased risk of pancreatic cancer in epidemiologic studies. However, BMI has usually been assessed at older ages, potentially underestimating the full impact of excess weight. We examined the association between BMI and pancreatic cancer mortality among 963,317 adults who were aged 30-89 years at their enrollment in Cancer Prevention Study II in 1982. During follow-up through 2014, a total of 8,354 participants died of pancreatic cancer. Hazard ratios per 5 BMI units, calculated using proportional hazards regression, declined steadily with age at BMI assessment, from 1.25 (95% confidence interval: 1.18, 1.33) in persons aged 30-49 years at enrollment to 1.13 (95% confidence interval: 1.02, 1.26) in those aged 70-89 years at enrollment (P for trend = 0.005). On the basis of a hazard ratio of 1.25 per 5 BMI units at age 45 years, we estimated that 28% of US pancreatic cancer deaths among persons born in 1970-1974 will be attributable to BMI ≥25.0-nearly twice the equivalent proportion of those born in the 1930s, a birth cohort with much lower BMI in middle age. These results suggest that BMI before age 50 years is more strongly associated with pancreatic cancer risk than BMI at older ages, and they underscore the importance of avoiding excess weight gain before middle age for preventing this highly fatal cancer., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study-II (CPS-II), and a meta-analysis of published cohort studies. Among 152 090 CPS-II participants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170 MDS were identified over 21 years of follow-up. In CPS-II, body mass index (BMI) was weakly associated with risk of CML (hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99-1·09 per 1 unit increase in BMI), AML (HR = 1·01, 95% CI: 0·98-1·03) and MDS (HR = 1·03, 95% CI: 0·99-1·07). After controlling for other anthropometric factors, no clear association was observed for height, BMI at age 18 years or weight change. In the meta-analysis (n = 7117 myeloid leukaemias), BMI 25-29·9 kg/m 2 (HR pooled  = 1·36, 95% CI: 1·12-1·59) and BMI ≥30 kg/m 2 (HR pooled  = 1·43, 95% CI: 1·18-1·69) were associated with higher risk of myeloid leukaemia overall, compared to a BMI <25 kg/m 2 . Likewise, BMI ≥25 kg/m 2 was positively associated with both AML and CML risk individually in the meta-analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer., Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis., Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95)., Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases., (© The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking. Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI). Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m 2 , HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m 2 , HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors. Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks. Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Remaining controversies on the association between body mass index (BMI) and mortality include the effects of smoking and prevalent disease on the association, whether overweight is associated with higher mortality rates, differences in associations by race and the optimal age at which BMI predicts mortality. To assess the relative risk (RR) of mortality by BMI in Whites and Blacks among subgroups defined by smoking, prevalent disease, and age, 891,572 White and 38,119 Black men and women provided height, weight and other information when enrolled in the Cancer Prevention Study II in 1982. Over 28 years of follow-up, there were 434,400 deaths in Whites and 18,702 deaths in Blacks. Cox proportional-hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI). Smoking and prevalent disease status significantly modified the BMI-mortality relationship in Whites and Blacks; higher BMI was most strongly associated with higher risk of mortality among never smokers without prevalent disease. All levels of overweight and obesity were associated with a statistically significantly higher risk of mortality compared to the reference category (BMI 22.5-24.9 kg/m2), except among Black women where risk was elevated but not statistically significant in the lower end of overweight. Although absolute mortality rates were higher in Blacks than Whites within each BMI category, relative risks (RRs) were similar between race groups for both men and women (p-heterogeneity by race  = 0.20 for men and 0.23 for women). BMI was most strongly associated with mortality when reported before age 70 years. Results from this study demonstrate for the first time that the BMI-mortality relationship differs for men and women who smoke or have prevalent disease compared to healthy never-smokers. These findings further support recommendations for maintaining a BMI between 20-25 kg/m2 for optimal health and longevity.

Background: The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity., Methods and Findings: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report., Conclusions: Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary.

Purpose: High body mass index (BMI) is an established risk factor for postmenopausal breast cancer. However, less is known about associations with waist circumference. In particular, it is unclear whether a larger waist circumference is associated with risk more than would be expected based solely on its contribution to BMI., Methods: We examined the associations of BMI and waist circumference with risk of postmenopausal breast cancer, with and without mutual adjustment, in the Cancer Prevention Study-II Nutrition Cohort. Analyses included 28,965 postmenopausal women who reported weight and waist circumference on a questionnaire in 1997 and were not taking menopausal hormones., Results: During a median follow-up of 11.58 years, 1,088 invasive breast cancer cases were identified. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated from multivariable-adjusted Cox proportional hazard regression models. Without adjustment for BMI, a larger waist circumference was associated with higher risk of breast cancer (per 10 cm increase in waist circumference, HR = 1.13, 95 % CI 1.08-1.19). However, adjustment for BMI eliminated the association with waist circumference (per 10 cm HR = 1.00, 95 % CI 0.92-1.08). BMI was associated with risk unadjusted for waist circumference (per 1 kg/m(2) HR = 1.04, 95 % CI 1.03-1.05) and adjusted for waist circumference (per 1 kg/m(2) HR = 1.04, 95 % CI 1.02-1.06)., Conclusions: Our study of predominantly white women provides evidence that a larger waist circumference is associated with higher risk of postmenopausal breast cancer, but not beyond its contribution to BMI.

Background: The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors., Methods: In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided., Results: Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86)., Conclusions: Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.

Results from epidemiologic studies examining associations between body size and risk of non-Hodgkin lymphoma (NHL) are inconsistent, and etiology may vary by histologic subtype of disease. Using Cox proportional hazards regression, multivariable relative risks (RRs) and 95% confidence intervals (CIs) were computed for associations of body mass index (BMI) and height with NHL in the prospective American Cancer Society Cancer Prevention Study-II Nutrition Cohort. From 1992 to 2007, 2074 incident cases of NHL were identified among 152 423 men and women. Obese individuals (BMI ≥ 30 kg/m(2)) had 23% higher incidence of NHL (95% CI 1.08-1.40) compared to those with normal weight (BMI 18.5-< 25 kg/m(2)). Height was positively associated with NHL (RR = 1.25, 95% CI 1.10-1.43, sex-specific quintile 5 vs. 1). BMI associations were strongest for diffuse large B-cell lymphoma. Height was most strongly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma and to a lesser extent with multiple myeloma. These findings provide further evidence that body size may play a role in the etiology of NHL, which is of public health importance given the rapid rise in obesity worldwide.

Background: Results of a pooled analysis of case-control studies show a higher risk of head and neck cancer (HNC) associated with a low body mass index (BMI) and a lower risk associated with being overweight or obese compared with being normal weight. However, these results are prone to bias due to residual confounding by smoking, a strong risk factor, and possible weight loss prior to diagnosis. Using prospectively collected data from the Cancer Prevention Study-II cohort and the Nutrition cohort, we examined the association of BMI with HNC mortality and incidence, overall and by smoking status., Methods: Mortality analyses included 1,383 cases among 1,059,153 participants; incidence analyses included 340 cases among 150,262 participants. Multivariable Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI) for the association of BMI with HNC incidence and mortality., Results: Overall, compared with the category of BMI 22.5-24.9 kg/m(2), the categories of BMI 25.0-29.9 kg/m(2) and ≥ 30.0 kg/m(2) were associated with a lower risk of HNC mortality but not incidence. In never smokers, there were no associations of BMI with HNC incidence or mortality. In smokers, BMI < 22.5 kg/m(2) was associated with a higher risk of HNC mortality (HR = 1.42, 95% CI, 1.20-1.67)., Conclusions: In this prospective cohort, there was no association between BMI and HNC incidence, although BMI was inversely associated with HNC mortality in smokers., Impact: These suggest that there is no etiologic relationship between BMI and HNC., (©2012 AACR.)

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.

Purpose: The impact of body mass index (BMI) on survival after colorectal cancer diagnosis is poorly understood. This study assessed the association of pre- and postdiagnosis BMI with all-cause and cause-specific survival among men and women diagnosed with colorectal cancer in a prospective cohort., Patients and Methods: Participants in the Cancer Prevention Study-II Nutrition Cohort reported weight and other risk factor information via a self-administered questionnaire at baseline in 1992 to 1993. Updated information on current weight and incident cancer was reported via periodic follow-up questionnaires. This analysis includes 2,303 cohort participants who were diagnosed with nonmetastatic colorectal cancer between baseline and mid 2007 and were observed for mortality from diagnosis through December 2008., Results: A total of 851 participants with colorectal cancer died during the 16-year follow-up period, including 380 as a result of colorectal cancer and 153 as a result of cardiovascular disease (CVD). In analyses of prediagnosis BMI (weight reported at baseline in 1992 to 1993; mean, 7 years before colorectal cancer diagnosis), obese BMI (≥ 30 kg/m(2)) relative to normal BMI (18.5 to 24.9 kg/m(2)) was associated with higher risk of mortality resulting from all causes (relative risk [RR], 1.30; 95% CI, 1.06 to 1.58), colorectal cancer (RR, 1.35; 95% CI, 1.01 to 1.80), and CVD (RR, 1.68; 95% CI, 1.07 to 2.65). Postdiagnosis BMI (based on weight reported; mean, 1.5 years after diagnosis) was not associated with all-cause or cause-specific mortality., Conclusion: This study suggests that prediagnosis BMI, but not postdiagnosis BMI, is an important predictor of survival among patients with nonmetastatic colorectal cancer.

Objective: Few studies have explored the potential association between body mass index (BMI) and non-Hodgkin lymphoma (NHL) according to histologic subtypes, or have evaluated BMI at different periods in the subject's life, and the results of these studies have been inconsistent., Subjects: A population-based, case-control study of 387 patients with NHL and 535 controls conducted in Nebraska between 1999 and 2002., Methods: Information on usual adult weight, weight at the ages 20-29, 40-49, and 60-69 years, height, physical activity, and other lifestyle factors was collected by telephone interview. A self-administered semi-quantitative food frequency questionnaire was used to collect dietary intake. Risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, total energy intake, physical activity, and other confounding factors., Results: Higher adult BMI was associated with risk of NHL (OR=1.4; 95% CI=0.9-2.0) comparing the obese group (BMI >or= 30.0 kg/m(2)) with the normal weight group (BMI=18.5-24.9 kg/m(2)). The risk was higher for those who were class 2 obese (BMI >or= 35.0 kg/m(2), OR=1.7; 95% CI=1.0-2.9). The positive association was similar among men and women. An excess risk of NHL was associated with high BMI at ages 40-49 years (OR=1.6; 95% CI=1.0-2.5), and to a lesser extent, at ages 20-29 years (OR=1.4; 95% CI=0.8-2.5). Obesity at ages 40-49 years was also associated with a higher risk of small lymphocytic lymphoma (OR=4.5; 95% CI=1.5-13.3), diffuse large B-cell NHL (OR=1.8; 95% CI=0.9-3.9) and follicular NHL (OR=1.8; 95% CI=0.9-3.5)., Conclusion: Obesity is associated with risk of NHL overall. Obesity at ages 40-49 years is also associated with a higher risk of NHL overall, and particularly small lymphocytic, follicular, and diffuse large B-cell NHL.

Serum testosterone concentration appears to be higher in black men than white men, particularly at younger ages. The higher incidence of prostate cancer in blacks has been attributed, at least in part, to this difference. Other factors associated with androgen levels in men include age and obesity. However, most of the studies of adult androgen levels are limited by their cross-sectional design. We conducted longitudinal analyses (Generalized Estimating Equation) of the associations of age, body mass index (BMI), and waist circumference with total and free testosterone and sex hormone-binding globulin (SHBG) concentrations during an 8-year period and compared these hormonal factors between black (n = 483) and white (n = 695) male participants of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. For men ages 24 years and older at the time of the first hormone measurement, increasing age was associated with a statistically significant decrease in serum total and free testosterone and an increase in SHBG (P < 0.05). BMI and waist circumference were inversely associated with total testosterone and SHBG, but only BMI was inversely associated with free testosterone. After adjustment for age and BMI, total testosterone was higher in blacks (0.21 ng/ml; P = 0.028) than whites, an approximately 3% difference. However, after further adjustment for waist circumference, there was no black-white difference (0.05 ng/ml; P = 0.62). These results indicate that the age-associated decrease in circulating testosterone and increase in SHBG begin during the 3rd decade of life, and that increasing obesity, particularly central obesity, is associated with decreasing total testosterone and SHBG. Results also suggest that the previously observed difference in total testosterone between black and white men could be attributed, for the most part, to racial differences in abdominal obesity.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to

BackgroundIn addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear.MethodsWe conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium.ResultsAll sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer.ConclusionsWe confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.

Background: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk.Methods: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided.Results: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes.Conclusion: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women. [ABSTRACT FROM AUTHOR]

The prevalence of excess body weight and the associated cancer burden have been rising over the past several decades globally. Between 1975 and 2016, the prevalence of excess body weight in adults-defined as a body mass index (BMI) ≥ 25 kg/m2 -increased from nearly 21% in men and 24% in women to approximately 40% in both sexes. Notably, the prevalence of obesity (BMI ≥ 30 kg/m2 ) quadrupled in men, from 3% to 12%, and more than doubled in women, from 7% to 16%. This change, combined with population growth, resulted in a more than 6-fold increase in the number of obese adults, from 100 to 671 million. The largest absolute increase in obesity occurred among men and boys in high-income Western countries and among women and girls in Central Asia, the Middle East, and North Africa. The simultaneous rise in excess body weight in almost all countries is thought to be driven largely by changes in the global food system, which promotes energy-dense, nutrient-poor foods, alongside reduced opportunities for physical activity. In 2012, excess body weight accounted for approximately 3.9% of all cancers (544,300 cases) with proportion varying from less than 1% in low-income countries to 7% or 8% in some high-income Western countries and in Middle Eastern and Northern African countries. The attributable burden by sex was higher for women (368,500 cases) than for men (175,800 cases). Given the pandemic proportion of excess body weight in high-income countries and the increasing prevalence in low- and middle-income countries, the global cancer burden attributable to this condition is likely to increase in the future. There is emerging consensus on opportunities for obesity control through the multisectoral coordinated implementation of core policy actions to promote an environment conducive to a healthy diet and active living. The rapid increase in both the prevalence of excess body weight and the associated cancer burden highlights the need for a rejuvenated focus on identifying, implementing, and evaluating interventions to prevent and control excess body weight. [ABSTRACT FROM AUTHOR]

Physical activity has been associated with lower lung cancer risk in numerous studies with estimates ranging from 20 to 50% lower risk in the most versus the least active study participants. Underweight and obesity have also been associated with lower lung cancer risk, with a nonlinear, inverted U-shaped relationship. However, associations of physical activity and obesity with lung cancer are likely significantly confounded by smoking since individuals who smoke are generally less active and leaner than non-smokers, but few studies have examined these associations stratified by smoking status. Using data from 162,679 men and women who were cancer-free at enrollment (1992-1993) in the American Cancer Society Cancer Prevention Study-II Nutrition Cohort, we examined associations of baseline recreational physical activity (MET-hours per week; none, 0.1 to <8.75 (reference), 8.75-17.4, 17.5+ MET-hours/week), baseline body mass index (BMI, weight (kg)/height (m2); <18.5, 18.5-22.0 (reference), 22.1-24.9, 25.0-29.9, 30.0+ kg/m2), and waist circumference (measured in 1997; sex-specific quartiles) in relation to lung cancer risk stratified by smoking status and years since quitting among former smokers (never, current, former <10 years, former, 10-19 years, former 20+ years). Cox proportional hazards modeling computed hazard rate ratios (RR) and 95% confidence intervals (CI) while adjusting for potential confounders. During 2,384,546 person years of follow-up time, 4,669 men and women were diagnosed with lung cancer (453 among never smokers; 1,452 among current smokers; 1,194 among former smokers <10 years since quitting; 725 among former 10-19 years; and 845 among former 20+ years). Physical activity was not associated with lung cancer risk within any of the smoking strata except in former smokers less than 10 years since quitting (RR = 0.77; 95% CI 0.67-0.90 for 17.5+ MET-hours/week). Similarly, BMI was inversely associated with lung cancer in former smokers less than 10 years since quitting (RR = 0.68; 95% CI 0.55-0.84 for 30+ kg/m2) and more modestly in former smokers who quit 10-19 and 20+ years ago. Waist circumference was not associated with lung cancer risk in any smoking category. While being physically active and maintaining a healthy body weight are important for prevention of various chronic diseases, including several types of cancer, our results suggest that physical activity, BMI, and waist circumference are not associated with lung cancer risk, regardless of smoking status. [ABSTRACT FROM AUTHOR]

Background: Prospective cohort studies contribute importantly to understanding the role of lifestyle, genetic, and other factors in chronic disease etiology.Methods: The American Cancer Society (ACS) recruited a new prospective cohort study, Cancer Prevention Study 3 (CPS-3), between 2006 and 2013 from 35 states and Puerto Rico. Enrollment took place primarily at ACS community events and at community enrollment "drives." At enrollment sites, participants completed a brief survey that included an informed consent, identifying information necessary for follow-up, and key exposure information. They also provided a waist measure and a nonfasting blood sample. Most participants also completed a more comprehensive baseline survey at home that included extensive medical, lifestyle, and other information. Participants will be followed for incident cancers through linkage with state cancer registries and for cause-specific mortality through linkage with the National Death Index.Results: In total, 303,682 participants were enrolled. Of these, 254,650 completed the baseline survey and are considered "fully" enrolled; they will be sent repeat surveys periodically for at least the next 20 years to update exposure information. The remaining participants (n = 49,032) will not be asked to update exposure information but will be followed for outcomes. Twenty-three percent of participants were men, 17.3% reported a race or ethnicity other than "white," and the median age at enrollment was 47 years.Conclusions: CPS-3 will be a valuable resource for studies of cancer and other outcomes because of its size; its diversity with respect to age, ethnicity, and geography; and the availability of blood samples and detailed questionnaire information collected over time. Cancer 2017;123:2014-2024. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Calcium intake may be important for bone health, but its effects on other outcomes, including cardiovascular disease (CVD) and cancer, remain unclear. Recent reports of adverse cardiovascular effects of supplemental calcium have raised concerns. Objective: We investigated associations of supplemental, dietary, and total calcium intakes with all-cause, CVD-specific, and cancer-specific mortality in a large, prospective cohort. Design: A total of 132,823 participants in the Cancer Prevention Study II Nutrition Cohort, who were followed from baseline (1992 or 1993) through 2012 for mortality outcomes, were included in the analysis. Dietary and supplemental calcium information was first collected at baseline and updated in 1999 and 2003. Multivariable-adjusted Cox proportional hazards models with cumulative updating of exposures were used to calculate RRs and 95% CIs for associations between calcium intake and mortality. Results: During a mean follow-up of 17.5 y, 43,186 deaths occurred. For men, supplemental calcium intake was overall not associated with mortality outcomes (P-trend > 0.05 for all), but men who were taking ≥1000 mg supplemental calcium/d had a higher risk of all-cause mortality (RR: 1.17; 95% CI: 1.03, 1.33), which was primarily attributed to borderline statistically significant higher risk of CVD-specific mortality (RR: 1.22; 95% CI: 0.99, 1.51). For women, supplemental calcium was inversely associated with mortality from all causes [RR (95% CI): 0.90 (0.87, 0.94), 0.84 (0.80, 0.88), and 0.93 (0.87, 0.99) for intakes of 0.1 to <500, 500 to <1000, and ≥1000 mg/d, respectively; P-trend < 0.01]. Total calcium intake was inversely associated with mortality in women (P-trend < 0.01) but not in men; dietary calcium was not associated with all-cause mortality in either sex. Conclusions: In this cohort, associations of calcium intake and mortality varied by sex. For women, total and supplemental calcium intakes are associated with lower mortality, whereas for men, supplemental calcium intake ≥1000 mg/d may be associated with higher all-cause and CVD-specific mortality. [ABSTRACT FROM AUTHOR]

Weight cycling, which consists of repeated cycles of intentional weight loss and regain, is common among individuals who try to lose weight. Some evidence suggests that weight cycling may affect biological processes that could contribute to carcinogenesis, but whether it is associated with cancer risk is unclear. Using 62,792 men and 69,520 women enrolled in the Cancer Prevention Study II Nutrition Cohort in 1992, we examined the association between weight cycling and cancer incidence. Weight cycles were defined by using baseline questions that asked the number of times ≥10 pounds (4.54 kg) was purposely lost and later regained. Multivariable-adjusted hazard ratios and 95% confidence intervals for all cancer and 15 individual cancers were estimated by using Cox proportional hazards regression. During up to 17 years of follow-up, 15,333 men and 9,984 women developed cancer. Weight cycling was not associated with overall risk of cancer in men (hazard ratio = 0.96, 95% confidence interval: 0.83, 1.11 for ≥20 cycles vs. no weight cycles) or women (hazard ratio = 0.96, 95% confidence interval: 0.86, 1.08) in models that adjusted for body mass index and other covariates.Weight cycling was also not associated with any individual cancer investigated. These results suggest that weight cycling, independent of body weight, is unlikely to influence subsequent cancer risk. [ABSTRACT FROM AUTHOR]

Multiple myeloma ( MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1·5 million participants (including 1388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios ( HRs) and 95% confidence intervals ( CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index ( BMI; HR = 1·22, 95% CI: 1·09-1·35 per 5 kg/m2) and for higher cohort-entry BMI ( HR 1·09, 95% CI: 1·03-1·16 per 5 kg/m2) and waist circumference ( HR = 1·06, 95% CI: 1·02-1·10 per 5 cm). Women who were the heaviest, both in early adulthood ( BMI 25+) and at cohort entry ( BMI 30+) were at greater risk compared to those with BMI 18·5 ≤ 25 at both time points ( HR = 1·95, 95% CI: 1·33-2·86). Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood. [ABSTRACT FROM AUTHOR]

: In a pooled analysis of 20 prospective studies, Cari Kitahara and colleagues find that class III obesity (BMI of 40–59) is associated with excess rates of total mortality, particularly due to heart disease, cancer, and diabetes. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background & Aims: Type 2 diabetes mellitus (DM) is associated with an increased risk of colorectal cancer (CRC); it is not clear if this association varies by sex or other factors. Insulin use might also be associated with CRC risk. We investigated associations of type 2 DM and insulin use with CRC risk. Methods: The Cancer Prevention Study II Nutrition Cohort is a prospective study of cancer incidence. In 1992 or 1993, adult participants (n = 184,194) completed a detailed, self-administered questionnaire. Follow-up questionnaires were sent in 1997 and every 2 years thereafter. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for covariates. Results: After exclusions, 73,312 men and 81,663 women remained in the final analytic cohort; 1567 men (227 with type 2 DM) and 1242 women (108 with type 2 DM) were diagnosed with colon or rectal cancer by 2007. Among men, type 2 DM was associated with increased risk of incident CRC compared to not having type 2 DM (RR: 1.24; 95% CI: 1.08−1.44); risk was higher for participants with type 2 DM using insulin (RR: 1.36; 95% CI: 1.05−1.78), and participants with type 2 DM not using insulin (RR: 1.22, 95% CI: 1.04−1.45). Among women, type 2 DM and insulin use were not associated with risk of incident CRC (RR: 1.01; 95% CI: 0.82−1.23 and RR: 0.95; 95% CI: 0.64−1.41, respectively). Conclusions: There is a modest association between type 2 DM and CRC among men, but not women. Insulin use is not associated with a substantially increased risk of CRC. [ABSTRACT FROM AUTHOR]

The article discusses a research study about the association between waist circumference (WC) and all-cause mortality in a large U.S. cohort. The researchers found high levels of association of WC with an approximately two-fold higher risk of mortality in men and women after adjustment of body mass index (BMI) and other risk factors. Among men, normal, overweight and obese BMI categories, the study found a positive association between WC and mortality.

Abstract: Context: Molecular and cell biology studies have demonstrated an association between bone and arterial wall disease, but the significance of a population-level association is less clear and potentially confounded by inability to account for shared risk factors. Objective: To test population-level associations between atherosclerosis types and bone integrity. Main outcome measures: Volumetric trabecular lumbar bone mineral density (vBMD), ankle-brachial index (ABI), intima-media thickness (IMT) of the common carotid (CCA-IMT) and internal carotid (ICA-IMT) arteries, and carotid plaque echogenicity. Design, setting and participants: A random subset of participants from the Multi-Ethnic Study of Atherosclerosis (MESA) assessed between 2002 and 2005. Results: 904 post-menopausal female (62.4 years; 62% non-white; 12% ABI <1; 17% CCA-IMT >1mm; 33% ICA-IMT >1mm) and 929 male (61.4 years; 58% non-white; 6% ABI <1; 25% CCA-IMT >1mm; 40% ICA-IMT >1mm) were included. In serial, sex-specific regression models adjusting for age, ethnicity, body mass index, dyslipidemia, hypertension, smoking, alcohol consumption, diabetes, homocysteine, interleukin-6, sex hormones, and renal function, lower vBMD was associated with lower ABI in men (p for trend <0.01) and greater ICA-IMT in men (p for trend <0.02). CCA-IMT was not associated with vBMD in men or women. Carotid plaque echogenicity was independently associated with lower vBMD in both men (trend p =0.01) and women (trend p <0.04). In all models, adjustment did not materially affect results. Conclusions: Lower vBMD is independently associated with structural and functional measures of atherosclerosis in men and with more advanced and calcified carotid atherosclerotic plaques in both sexes. [Copyright &y& Elsevier]