Abstract
Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.
Highlights
Endometrial cancer (EC), a cancer of the uterine epithelial lining that typically occurs near or after menopause, is the most common cancer of the female reproductive organs and the 10th leading cause of cancer death in women in the developed world [1,2,3]
Mean age at diagnosis for cases ranged from 58.5 years in Alberta Health Services Study (AHS) to 65.5 years in Multiethnic Cohort Study (MEC) and mean BMI at diagnosis for cases ranged from 28.8 kg/m2 in MEC to 32.3 kg/m2 in AHS and EDGE
We present an initial exploration into whether rare variants are associated with EC risk in a multiethnic population from the E2C2
Summary
Endometrial cancer (EC), a cancer of the uterine epithelial lining that typically occurs near or after menopause, is the most common cancer of the female reproductive organs and the 10th leading cause of cancer death in women in the developed world [1,2,3]. EC is strongly associated with estrogen-only post-menopausal hormone therapy [4,5] and excess body weight [6] due to increased aromatization of C-19 steroids by excess adipose tissue [7]. Study Alberta Health Services Estrogen, Diet, Genetics and Endometrial Cancer Fred Hutchinson Cancer Research Center Multiethnic Cohort Study *Sample size before quality control. Study Alberta Health Services Estrogen, Diet, Genetics and Endometrial Cancer Fred Hutchinson Cancer Research Center Multiethnic Cohort Study *Sample size before quality control. doi:10.1371/journal.pone.0097045.t001
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