Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Cancer Res. 2016 Sep 1;76(17):5103-14. doi: 10.1158/0008-5472.CAN-15-2980. Epub 2016 Apr 20.

Abstract

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / genetics*
  • Colorectal Neoplasms / genetics*
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Ovarian Neoplasms / genetics*
  • Prostatic Neoplasms / genetics*