Jason Wong

Sc.D

National Cancer Institute

Postdoctoral Fellow

PLCO (Learn more about this study)

PLCO-184

Jan 8, 2016

The interaction between genome-wide polymorphisms, progestin-use, and vitamin D intake in modifying risk of endometrial cancer

Despite the growing body of evidence pertaining to genetic, reproductive, and dietary risk factors of Endometrial Cancer, the nature in which these aspects are intertwined is largely unknown. Furthering the understanding of these complex relationships would be beneficial in the ongoing effort to devise preventative measures to improve the reproductive health of women worldwide. Therefore, the purpose of this study is to assess the interaction between progestin exposure, common genetic polymorphisms throughout the genome, and Vitamin D levels in modifying risk of Endometrial Cancer. Given the methodological challenges of evaluating multiple interactions, we will leverage the Epidemiology of Endometrial Cancer Consortium (E2C2) comprised of over 8000 endometrial cancer cases and 24 000 controls, from 21 case-control and 24 cohort studies across North America, Asia, Europe, and Australia.

This study will use a case-control design to address aims 1, 2, and 3.

Incident and prevalent cases of invasive endometrial cancer (code 11-19, subcode 3-8) will be sampled from each study. Cases in Stage 1 were diagnosed with Type I EC. In cohort studies, controls were cancer free at the time of case diagnosis. In case–control studies, controls had not had hysterectomies. The cohort studies were analyzed as nested case–control studies. Cases of European descent from CTS, CONN, FHRC, MEC, NHS and PLCO were scanned using Illumina Omniexpress. PLCO controls were scanned using Illumina Omni 2.5 and the PECS cases and controls were scanned using Illumina Human 660 W. With the exception of PLCO, all controls were matched to cases on age within each study site. Each participating study obtained informed consent from study participants and approval from its institutional review board (IRB) for this study and obtained IRB certification permitting data sharing in accordance with the NIH Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association studies (GWAS). Participating studies in Stage 2 are described in Table 1. We did not restrict to European ancestry in this stage; a multiethnic population was included, although we also conducted sensitivity analyses restricted to women of European ancestry. We conducted two replications, a fast track, in which nine SNPs were genotyped in all studies except ANECS, SEARCH and SECGS using the Taqman assay. Stage 2 was conducted using the Illumina’s Human Exome 12v1 chip with custom content in the following studies: AHS, FHCRC, MEC and EDGE.

Specific Aims:

1) To determine if common single nucleotide polymorphisms throughout the genome, with particular focus on those in the progesterone receptor and estrogen receptor genes modifies the effect of progestin-use on Endometrial Cancer risk.

2) To assess the interaction between common single nucleotide polymorphisms throughout the genome, with particular focus on those in the progesterone receptor and estrogen receptor genes, and predicted serum Vitamin D levels in modifying risk of Endometrial Cancer.

3) To determine if predicted serum Vitamin D levels modifies the effect of progestin-use on Endometrial Cancer risk.

Northshore Medical
Gustavo Rodriguez

Alberta EnDometrial Cancer and Physical Activity
ChristineFriedenreich

California Teachers Study
Peggy Reynolds

Connecticut Endometrial Cancer Study
Herbert Yu

Estrogen, Diet, Genetics, and Endometrial Cancer
Sara H.Olson

FHCRC Endometrial Cancer Case-Control Studies
Chu Chen

Multiethnic Cohort Study
Veronica Wendy Setiawan

Nurses' Health Study
Immaculata De Vivo

Polish Case Control Study (NCI)
Nicolas Wentzensen

Prostate Lung Colorectal Ovarian NCI Study
Nicolas Wentzensen