Common variants at 19p13 are associated with susceptibility to ovarian cancer.
Bolton KL., Tyrer J., Song H., Ramus SJ., Notaridou M., Jones C., Sher T., Gentry-Maharaj A., Wozniak E., Tsai Y-Y., Weidhaas J., Paik D., Van Den Berg DJ., Stram DO., Pearce CL., Wu AH., Brewster W., Anton-Culver H., Ziogas A., Narod SA., Levine DA., Kaye SB., Brown R., Paul J., Flanagan J., Sieh W., McGuire V., Whittemore AS., Campbell I., Gore ME., Lissowska J., Yang HP., Medrek K., Gronwald J., Lubinski J., Jakubowska A., Le ND., Cook LS., Kelemen LE., Brooks-Wilson A., Massuger LFAG., Kiemeney LA., Aben KKH., van Altena AM., Houlston R., Tomlinson I., Palmieri RT., Moorman PG., Schildkraut J., Iversen ES., Phelan C., Vierkant RA., Cunningham JM., Goode EL., Fridley BL., Kruger-Kjaer S., Blaeker J., Hogdall E., Hogdall C., Gross J., Karlan BY., Ness RB., Edwards RP., Odunsi K., Moyisch KB., Baker JA., Modugno F., Heikkinenen T., Butzow R., Nevanlinna H., Leminen A., Bogdanova N., Antonenkova N., Doerk T., Hillemanns P., Dürst M., Runnebaum I., Thompson PJ., Carney ME., Goodman MT., Lurie G., Wang-Gohrke S., Hein R., Chang-Claude J., Rossing MA., Cushing-Haugen KL., Doherty J., Chen C., Rafnar T., Besenbacher S., Sulem P., Stefansson K., Birrer MJ., Terry KL., Hernandez D., Cramer DW., Vergote I., Amant F., Lambrechts D., Despierre E., Fasching PA., Beckmann MW., Thiel FC., Ekici AB., Chen X., Australian Ovarian Cancer Study Group None., Australian Cancer Study (Ovarian Cancer) None., Ovarian Cancer Association Consortium None., Johnatty SE., Webb PM., Beesley J., Chanock S., Garcia-Closas M., Sellers T., Easton DF., Berchuck A., Chenevix-Trench G., Pharoah PDP., Gayther SA.
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.