The waist-hip ratio offers additional prognostic information beyond BMI and waist circumference.

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.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1 . In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P <5×10 −8 , bringing the number of known independent signals for CRC to approximately 100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs, somatic drivers, and support a role of immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of underlying biology, and impact personalized screening strategies and drug development.

Background: Indoor tanning has been only weakly associated with melanoma risk; most reports were unable to adjust for sun exposure, confirm a dose-response, or examine specific tanning devices. A populationbased case-control study was conducted to address these limitations.Methods: Cases of invasive cutaneous melanoma, diagnosed in Minnesota between 2004 and 2007 at ages 25 to 59, were ascertained from a statewide cancer registry; age-matched and gender-matched controls were randomly selected from state driver's license lists. Self-administered questionnaires and telephone interviews included information on ever use of indoor tanning, types of device used, initiation age, period of use, dose, duration, and indoor tanning-related burns. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for known melanoma risk factors.Results: Among 1,167 cases and 1,101 controls, 62.9% of cases and 51.1% of controls had tanned indoors (adjusted OR 1.74; 95% CI, 1.42-2.14). Melanoma risk was pronounced among users of UVB-enhanced (adjusted OR, 2.86; 95% CI, 2.03-4.03) and primarily UVA-emitting devices (adjusted OR, 4.44; 95% CI, 2.45-8.02). Risk increased with use: years (P < 0.006), hours (P < 0.0001), or sessions (P = 0.0002). ORs were elevated within each initiation age category; among indoor tanners, years used was more relevant for melanoma development.Conclusions: In a highly exposed population, frequent indoor tanning increased melanoma risk, regardless of age when indoor tanning began. Elevated risks were observed across devices.Impact: This study overcomes some of the limitations of earlier reports and provides strong support for the recent declaration by the IARC that tanning devices are carcinogenic in humans. Cancer Epidemiol Biomarkers

SummaryBackgroundMenarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.MethodsIndividual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.FindingsBreast cancer risk increased by a factor of 1·050 (95% CI 1·044–1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025–1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45–54 years 1·43, 1·33–1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).InterpretationThe effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.FundingCancer Research UK.

This study suggests that smoking cigarettes statistically significantly contributes to MSI in colon tumors. We estimate that approximately 21% of MSI in colon tumors may be attributable to cigarette smoking.

BACKGROUND The authors tested the hypothesis that the metabolic syndrome (≥3 of the following components: high blood pressure, increased waist circumference, hypertriglyceridemia, low levels of high‐density lipoprotein cholesterol, or diabetes/hyperglycemia) is a risk factor for colorectal cancer. METHODS Data from the Atherosclerosis Risk in Communities (ARIC) multicenter prospective cohort study were used. Metabolic syndrome components and other risk factors were collected during 1987 to 1989 from the 14,109 men and women in these analyses. One hundred ninety‐four incident colorectal cancers were identified through the Year 2000. Multivariate Cox proportional hazards regression analyses were used to examine associations. RESULTS Baseline metabolic syndrome (≥3 components vs. 0 components) had a positive association with age‐adjusted and gender‐adjusted colorectal cancer incidence (relative risk [RR], 1.49; 95% confidence interval [95%CI], 1.0‐2.4); this association was attenuated after multivariate adjustment (RR, 1.39; 95%CI, 0.9‐2.2). There was a dose‐response association between colorectal cancer incidence and the number of metabolic syndrome components present at baseline (P for trend = .006) after multivariate adjustment. Analysis of gender revealed that the multivariate‐adjusted association of metabolic syndrome with colorectal cancer was stronger in men (RR, 1.78; 95%CI, 1.0‐3.6) and weaker in women (RR, 1.16; 95%CI, 0.6‐2.2). CONCLUSIONS In this population‐based cohort, metabolic syndrome was a risk factor for incident colorectal cancer in men but not women. Evidence is growing that the metabolic syndrome may be a marker for a physiologic milieu of growth that encourages tumor initiation, promotion, and/or progression. Cancer 2006. © 2006 American Cancer Society.

SummaryBackgroundPublished findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.MethodsPrincipal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.FindingsDuring prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.InterpretationIf these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.FundingCancer Research UK and the Medical Research Council.