TY - JOUR

T1 - ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study

AU - Doherty, Jennifer A

AU - Rossing, Mary Anne

AU - Cushing-Haugen, Kara L

AU - Chen, Chu

AU - Van Den Berg, David J

AU - Wu, Anna H

AU - Pike, Malcolm C

AU - Ness, Roberta B

AU - Moysich, Kirsten

AU - Chenevix-Trench, Georgia

AU - Beesley, Jonathan

AU - Webb, Penelope M

AU - Chang-Claude, Jenny

AU - Wang-Gohrke, Shan

AU - Goodman, Marc T

AU - Lurie, Galina

AU - Thompson, Pamela J

AU - Carney, Michael E

AU - Hogdall, Estrid

AU - Kjaer, Susanne Kruger

AU - Hogdall, Claus

AU - Goode, Ellen L

AU - Cunningham, Julie M

AU - Fridley, Brooke L

AU - Vierkant, Robert A

AU - Berchuck, Andrew

AU - Moorman, Patricia G

AU - Schildkraut, Joellen M

AU - Palmieri, Rachel T

AU - Cramer, Daniel W

AU - Terry, Kathryn L

AU - Yang, Hannah P

AU - Garcia-Closas, Montserrat

AU - Chanock, Stephen

AU - Lissowska, Jolanta

AU - Song, Honglin

AU - Pharoah, Paul D P

AU - Shah, Mitul

AU - Perkins, Barbara

AU - McGuire, Valerie

AU - Whittemore, Alice S

AU - Di Cioccio, Richard A

AU - Gentry-Maharaj, Aleksandra

AU - Menon, Usha

AU - Gayther, Simon A

AU - Ramus, Susan J

AU - Ziogas, Argyrios

AU - Brewster, Wendy

AU - Anton-Culver, Hoda

AU - Pearce, Celeste Leigh

AU - Australian Ovarian Cancer Study Management Group

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

U2 - http://dx.doi.org/10.1158/1055-9965.EPI-09-0729

DO - http://dx.doi.org/10.1158/1055-9965.EPI-09-0729

M3 - Journal article

VL - 19

SP - 245

EP - 250

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 1

ER -