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

Author(s): Fehringer G,  Kraft P,  Pharoah PD,  Eeles RA,  Chatterjee N,  Schumacher FR,  Schildkraut JM,  Lindström S,  Brennan P,  Bickeböller H,  Houlston RS,  Landi MT,  Caporaso N,  Risch A,  Amin Al Olama A,  Berndt SI,  Giovannucci EL,  Grönberg H,  Kote-Jarai Z,  Ma J,  Muir K,  Stampfer MJ,  Stevens VL,  Wiklund F,  Willett WC,  Goode EL,  Permuth JB,  Risch HA,  Reid BM,  Bezieau S,  Brenner H,  Chan AT,  Chang-Claude J,  Hudson TJ,  Kocarnik JK,  Newcomb PA,  Schoen RE,  Slattery ML,  White E,  Adank MA,  Ahsan H,  Aittomäki K,  Baglietto L,  Blomquist C,  Canzian F,  Czene K,  Dos-Santos-Silva I,  Eliassen AH,  Figueroa JD,  Flesch-Janys D,  Fletcher O,  Garcia-Closas M,  Gaudet MM,  Johnson N,  Hall P,  Hazra A,  Hein R,  Hofman A,  Hopper JL,  Irwanto A,  Johansson M,  Kaaks R,  Kibriya MG,  Lichtner P,  Liu J,  Lund E,  Makalic E,  Meindl A,  Müller-Myhsok B,  Muranen TA,  Nevanlinna H,  Peeters PH,  Peto J,  Prentice RL,  Rahman N,  Sanchez MJ,  Schmidt DF,  Schmutzler RK,  Southey MC,  Tamimi R,  Travis RC,  Turnbull C,  Uitterlinden AG,  Wang Z,  Whittemore AS,  Yang XR,  Zheng W,  Buchanan DD,  Casey G,  Conti DV,  Edlund CK,  Gallinger S,  Haile RW,  Jenkins M,  Le Marchand L,  Li L,  Lindor NM,  Schmit SL,  Thibodeau SN,  Woods MO,  Rafnar T,  Gudmundsson J,  Stacey SN,  Stefansson K,  Sulem P,  Chen YA,  Tyrer JP,  Christiani DC,  Wei Y,  Shen H,  Hu Z,  Shu XO,  Shiraishi K,  Takahashi A,  Bossé Y,  Obeidat M,  Nickle D,  Timens W,  Freedman ML,  Li Q,  Seminara D,  Chanock SJ,  Gong J,  Peters U,  Gruber SB,  Amos CI,  Sellers TA,  Easton DF,  Hunter DJ,  Haiman CA,  Henderson BE,  Hung RJ,  Ovarian Cancer Association Consortium (OCAC),  PRACTICAL Consortium,  Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON),  Colorectal Transdisciplinary (CORECT) Study,  African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)

Journal: Cancer Res

Date: 2016 Sep 1

Major Program(s) or Research Group(s): PLCO

PubMed ID: 27197191

PMC ID: PMC5010493

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.