||Doherty JA, Rossing MA, Cushing-Haugen KL, Chen C, Van Den Berg DJ, Wu AH, Pike MC, Ness RB, Moysich K, Chenevix-Trench G, Beesley J, Webb PM, Chang-Claude J, Wang-Gohrke S, Goodman MT, Lurie G, Thompson PJ, Carney ME, Hogdall E, Kjaer SK, Hogdall C, Goode EL, Cunningham JM, Fridley BL, Vierkant RA, Berchuck A, Moorman PG, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Yang HP, Garcia-Closas M, Chanock S, Lissowska J, Song H, Pharoah PD, Shah M, Perkins B, McGuire V, Whittemore AS, Di Cioccio RA, Gentry-Maharaj A, Menon U, Gayther SA, Ramus SJ, Ziogas A, Brewster W, Anton-Culver H, Australian Ovarian Cancer Study Management Group, Australian Cancer Study (Ovarian Cancer), Pearce CL, Ovarian Cancer Association Consortium (OCAC)
||We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope 1 (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95% CI, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer.