Common variants at 19p13 are associated with susceptibility to ovarian cancer.

Publication Type:

Journal Article

Authors:

Bolton, Kelly L; Tyrer, Jonathan; Song, Honglin; Ramus, Susan J; Notaridou, Maria; Jones, Chris; Sher, Tanya; Gentry-Maharaj, Aleksandra; Wozniak, Eva; Tsai, Ya-Yu; Weidhaas, Joanne; Paik, Daniel; Van Den Berg, David J; Stram, Daniel O; Pearce, Celeste Leigh; Wu, Anna H; Brewster, Wendy; Anton-Culver, Hoda; Ziogas, Argyrios; Narod, Steven A; Levine, Douglas A; Kaye, Stanley B; Brown, Robert; Paul, Jim; Flanagan, James; Sieh, Weiva; McGuire, Valerie; Whittemore, Alice S; Campbell, Ian; Gore, Martin E; Lissowska, Jolanta; Yang, Hanna P; Medrek, Krzysztof; Gronwald, Jacek; Lubinski, Jan; Jakubowska, Anna; Le, Nhu D; Cook, Linda S; Kelemen, Linda E; Brook-Wilson, Angela; Massuger, Leon F A G; Kiemeney, Lambertus A; Aben, Katja K H; van Altena, Anne M; Houlston, Richard; Tomlinson, Ian; Palmieri, Rachel T; Moorman, Patricia G; Schildkraut, Joellen; Iversen, Edwin S; Phelan, Catherine; Vierkant, Robert A; Cunningham, Julie M; Goode, Ellen L; Fridley, Brooke L; Kruger-Kjaer, Susan; Blaeker, Jan; Hogdall, Estrid; Hogdall, Claus; Gross, Jenny; Karlan, Beth Y; Ness, Roberta B; Edwards, Robert P; Odunsi, Kunle; Moyisch, Kirsten B; Baker, Julie A; Modugno, Francesmary; Heikkinenen, Tuomas; Butzow, Ralf; Nevanlinna, Heli; Leminen, Arto; Bogdanova, Natalia; Antonenkova, Natalia; Doerk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Thompson, Pamela J; Carney, Michael E; Goodman, Marc T; Lurie, Galina; Wang-Gohrke, Shan; Hein, Rebecca; Chang-Claude, Jenny; Rossing, Mary Anne; Cushing-Haugen, Kara L; Doherty, Jennifer A; Chen, Chu; Rafnar, Thorunn; Besenbacher, Soren; Sulem, Patrick; Stefansson, Kari; Birrer, Michael J; Terry, Kathryn L; Hernandez, Dena; Cramer, Daniel W; Vergote, Ignace; Amant, Frederic; Lambrechts, Diether; Despierre, Evelyn; Fasching, Peter A; Beckmann, Matthias W; Thiel, Falk C; Ekici, Arif B; Chen, Xiaoqing; Johnatty, Sharon E; Webb, Penelope M; Beesley, Jonathan; Chanock, Stephen; Garcia-Closas, Montserrat; Sellers, Tom; Easton, Douglas F; Berchuck, Andrew; Chenevix-Trench, Georgia; Pharoah, Paul D P; Gayther, Simon A

Source:

Nature genetics, Volume 42, Issue 10, p.880-4 (2010)

Keywords:

2010, Adaptor Proteins, Signal Transducing, Adenocarcinoma, Clear Cell, Adenocarcinoma, Mucinous, Case-Control Studies, Center-Authored Paper, Chromosomes, Human, Pair 19, Cystadenocarcinoma, Serous, Endometrial Neoplasms, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Middle Aged, Oligonucleotide Array Sequence Analysis, Ovarian Neoplasms, Ovary, Polymorphism, Single Nucleotide, Public Health Sciences Division, Shared Resources, Specimen Processing Core Facility, Tumor Cells, Cultured, Tumor Markers, Biological

Abstract:

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10⁻⁴ and P = 6 × 10⁻⁴, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10⁻⁹ and P = 4 × 10⁻¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.