Type I and II endometrial cancers: have they different risk factors?

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 = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 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 < .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. (C) 2013 by American Society of Clinical Oncolog

Identification of nine new susceptibility loci for endometrial cancer

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study

Cancer prevention for global health: A report from the ASPO international cancer prevention interest group

As cancer incidence and mortality rates increase in low- and middle-income countries, the need for cancer prevention and control research directed to these countries becomes increasingly important. The American Society of Preventive Oncology (ASPO) is a community of professionals in cancer prevention and control whose mission is to "foster the continuing development of investigators and the exchange and translation of scientific information to reduce the cancer burden." In the session presented at the ASPO 36th Annual Meeting in Washington, DC in March 2012, chaired by Drs. Frank Meyskens and Dejana Braithwaite, Dr. Paolo Boffetta discussed some of the achievements in global cancer prevention and suggested that future efforts focus on three major causes of cancer: tobacco-use, infections, and overweight/obesity. Dr. Timothy Rebbeck presented an overview of prostate cancer research in sub-Saharan Africa and highlighted how the complex nature of prostate cancer etiology and outcomes can be addressed through capacity-building research partnerships. Cancer is an emerging public health challenge in developing countries because of the aging and expansion of the population and increased prevalence of cancer risk factors such as smoking, obesity, physical inactivity, and reproductive factors. There are opportunities to reduce the growing cancer burden through the development of research capacity and the application of resource-appropriate interventions. ©2012 AACR

Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse African hunter-gatherers

To reconstruct modern human evolutionary history and identify loci that have shaped hunter-gatherer adaptation, we sequenced the whole genomes of five individuals in each of three different hunter-gatherer populations at >60x coverage: Pygmies from Cameroon and Khoesan-speaking Hadza and Sandawe from Tanzania. We identify 13.4 million variants, substantially increasing the set of known human variation. We found evidence of archaic intro-gression in all three populations, and the distribution of time to most recent common ancestors from these regions is similar to that observed for introgressed regions in Europeans. Additionally, we identify numerous loci that harbor signatures of local adaptation, including genes involved in immunity, metabolism, olfactory and taste perception, reproduction, and wound healing. Within the Pygmy population, we identify multiple highly differentiated loci that play a role in growth and anterior pituitary function and are associated with height