TY - JOUR
T1 - Variation at 8q24 and 9p24 and risk of epithelial ovarian cancer
AU - White, Kristin L.
AU - Sellers, Thomas A.
AU - Fridley, Brooke L.
AU - Vierkant, Robert A.
AU - Phelan, Catherine M.
AU - Tsai, Ya Yu
AU - Kalli, Kimberly R.
AU - Berchuck, Andrew
AU - Iversen, Edwin S.
AU - Hartmann, Lynn C.
AU - Liebow, Mark
AU - Armasu, Sebastian
AU - Fredericksen, Zachary
AU - Larson, Melissa C.
AU - Duggan, David
AU - Couch, Fergus J.
AU - Schildkraut, Joellen M.
AU - Cunningham, Julie M.
AU - Goode, Ellen L.
N1 - Funding Information:
This work was supported by the National Cancer Institute [R01 CA122443, R01 CA88868, and R01 CA76016], the Ovarian Cancer Research Fund, and the Mayo Foundation. We thank Mr. Matt Kosel for statistical analysis, Dr. Paul P.D. Pharoah for advice on SNP selection, Ms. Ashley Pitzer and Ms. Karin Goodman for subject recruitment, and Ms. Katelyn Goodman for assistance with preparation of Tables and Figures.
PY - 2010/2
Y1 - 2010/2
N2 - The chromosome 8q24 region (specifically, 8q24.21.a) is known to harbor variants associated with risk of breast, colorectal, prostate, and bladder cancers. In 2008, variants rs10505477 and rs6983267 in this region were associated with increased risk of invasive ovarian cancer (p < 0.01); however, three subsequent ovarian cancer reports of 8q24 variants were null. Here, we used a multi-site case-control study of 940 ovarian cancer cases and 1,041 controls to evaluate associations between these and other single-nucleotide polymorphisms (SNPs) in this 8q24 region, as well as in the 9p24 colorectal cancer associated-region (specifically, 9p24.1.b). A total of 35 SNPs from previous reports and additional tagging SNPs were assessed using an Illumina GoldenGate array and analyzed using logistic regression models, adjusting for population structure and other potential confounders. We observed no association between genotypes and risk of ovarian cancer considering all cases, invasive cases, or invasive serous cases. For example, at 8q24 SNPs rs10505477 and rs6983267, analyses yielded per-allele invasive cancer odds ratios of 0.95 (95% confidence interval (CI) 0.82-1.09, p trend 0.46) and 0.97 (95% CI 0.84-1.12, p trend 0.69), respectively. Analyses using an approach identical to that of the first positive 8q24 report also yielded no association with risk of ovarian cancer. In the 9p24 region, no SNPs were associated with risk of ovarian cancer overall or with invasive or invasive serous disease (all p values > 0.10). These results indicate that the SNPs studied here are not related to risk of this gynecologic malignancy and that the site-specific nature of 8q24.21.a associations may not include ovarian cancer.
AB - The chromosome 8q24 region (specifically, 8q24.21.a) is known to harbor variants associated with risk of breast, colorectal, prostate, and bladder cancers. In 2008, variants rs10505477 and rs6983267 in this region were associated with increased risk of invasive ovarian cancer (p < 0.01); however, three subsequent ovarian cancer reports of 8q24 variants were null. Here, we used a multi-site case-control study of 940 ovarian cancer cases and 1,041 controls to evaluate associations between these and other single-nucleotide polymorphisms (SNPs) in this 8q24 region, as well as in the 9p24 colorectal cancer associated-region (specifically, 9p24.1.b). A total of 35 SNPs from previous reports and additional tagging SNPs were assessed using an Illumina GoldenGate array and analyzed using logistic regression models, adjusting for population structure and other potential confounders. We observed no association between genotypes and risk of ovarian cancer considering all cases, invasive cases, or invasive serous cases. For example, at 8q24 SNPs rs10505477 and rs6983267, analyses yielded per-allele invasive cancer odds ratios of 0.95 (95% confidence interval (CI) 0.82-1.09, p trend 0.46) and 0.97 (95% CI 0.84-1.12, p trend 0.69), respectively. Analyses using an approach identical to that of the first positive 8q24 report also yielded no association with risk of ovarian cancer. In the 9p24 region, no SNPs were associated with risk of ovarian cancer overall or with invasive or invasive serous disease (all p values > 0.10). These results indicate that the SNPs studied here are not related to risk of this gynecologic malignancy and that the site-specific nature of 8q24.21.a associations may not include ovarian cancer.
KW - Genome-wide association study
KW - Molecular epidemiology
KW - Neoplasms
KW - Polymorphisms
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U2 - 10.1375/twin.13.1.43
DO - 10.1375/twin.13.1.43
M3 - Article
C2 - 20158306
AN - SCOPUS:77953265316
SN - 1832-4274
VL - 13
SP - 43
EP - 56
JO - Twin Research and Human Genetics
JF - Twin Research and Human Genetics
IS - 1
ER -