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A B S T R A C T PurposeEndometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and MethodsIndividual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n ϭ 7,246), adenocarcinoma not otherwise specified (n ϭ 4,830), and adenocarcinoma with squamous differentiation (n ϭ 777) as type I tumors and serous (n ϭ 508) and mixed cell (n ϭ 346) as type II tumors. ResultsParity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m 2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity Ͻ .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. ConclusionThe results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.

An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).Patients and Methods Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competingrisks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. ResultsMost risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] , .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het # .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. ConclusionThe heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.

The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors.

Objective To assess the independent impact of waist circumference on mortality across the entire range of body mass index (BMI), and to estimate the loss in life expectancy related to a higher waist circumference. Methods We pooled data from 11 prospective cohort studies with 650,386 white adults aged 20–83 years and enrolled from January 1, 1986 through December 31, 2000. We used proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for the association of waist circumference with mortality. Results During a median follow-up of 9 years (maximum=21 years), 78,268 participants died. After accounting for age, study, BMI, smoking status, alcohol consumption, and physical activity, there was a strong positive linear association of waist circumference with all-cause mortality was observed for men (HR=1.52 for 110+ versus <90cm, 95%CI, 1.45–1.59; HR=1.07 per 5cm increment, 95%CI, 1.06–1.08) and women (HR=1.80 for 95+ versus <70cm, 95%CI, 1.70–1.89; HR=1.09 per 5cm increment, 95%CI, 1.08–1.09). The estimated decrease in life expectancy for highest versus lowest waist circumference was ~3 years for men and ~5 years for women. The HR per 5cm increment in waist circumference was similar for both sexes at all BMI levels from 20–50 kg/m2, but it was higher at younger ages, higher for longer follow-up, and lower among male current smokers. The associations were stronger for heart and respiratory disease mortality than for cancer. Conclusions In white adults, higher waist circumference was positively associated with higher mortality at all levels of BMI from 20–50 kg/m2. Waist circumference should be assessed in combination with BMI, even for those in the normal BMI range, as part of risk assessment for obesity-related premature mortality.

The overall 5‐year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence‐based, cancer‐specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer‐specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta‐analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health‐related behaviors and comorbidities, long‐term sequelae and patient‐reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.

Leukemias commonly arise as a result of DNA translocations, inversions, or deletions in genes regulating blood cell development or homeostasis. Folate deficiency has been associated with uracil misincorporation into DNA and DNA double strand breaks during uracil excision repair, thus increasing the risk of chromosomal aberrations. Methylenetetrahydrofolate reductase (MTHFR) directs 5,10-methylenetetrahydrofolate toward methionine synthesis at the expense of DNA synthesis. Two MTHFR polymorphisms, C677T and A1298C, have been associated with reduced enzyme activity and C677T with altered distribution of intracellular folate metabolites. Rapidly replicating cell types, such as hematopoietic cells, may be especially sensitive to changes in the availability of intracellular folate. Three case-control studies have evaluated the association between MTHFR polymorphisms and the risk of acute leukemia, and they suggest that both adults and children with the variant forms of MTHFR have a decreased risk of lymphoid leukemias. However, no modification in risk has been observed for myeloid leukemias, suggesting that differences in folate requirements or susceptibility to chromosomal damage may exist between myeloid and lymphoid cells. Further investigation into the association between MTHFR polymorphisms and the risk of leukemia is warranted. It should include larger sample sizes and other polymorphisms in folate metabolism and address interactions with folate status.

Background Although dietary supplements are commonly taken to avoid chronic disease, long-term health consequences of many compounds are unknown. Methods We assessed the use of vitamin and mineral supplements in relation to total mortality in 38 772 older women in the Iowa Women's Health Study, mean age 61.6 years at baseline in 1986. Supplement use was self-reported in 1986, 1997 and 2004. Through December 31, 2008, 15 594 deaths (40.2%) were identified through the State Health Registry of Iowa and the National Death Index. Results In multivariable adjusted proportional hazards regression models, the use of multivitamins (Hazard Ratio (HR), 1.06 [95% CI, 1.02-1.10], Absolute Risk Increase (ARI), 2.4%), vitamin B6 (HR, 1.10 [95% CI, 1.01-1.21], ARI, 4.1%), folic acid (HR, 1.15 [95% CI, 1.00-1.32], ARI, 5.9%), iron (HR, 1.10 [95% CI, 1.03-1.17], ARI, 3.9%), magnesium (HR, 1.08 [95% CI, 1.01-1.15], ARI, 3.6%), zinc (HR, 1.08 [95% CI, 1.01-1.15], ARI, 3.0%) and copper (HR, 1.45 [95% CI, 1.20-1.75], ARI, 18.0%) were associated with increased risk of total mortality when compared with corresponding nonusers, while calcium was inversely related (HR, 0.91 [95% CI, 0.88-0.94], Absolute Risk Reduction (ARR), 3.8%). Findings for iron and calcium were replicated in separate shorter-term analyses (10-year, 6-year and 4-year follow-up) each with about 15% dead, starting in 1986, 1997, and 2004. Conclusion In older women several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality risk, most strongly supplemental iron, while calcium, in contrast to many studies, was associated with decreased risk.