Variation at 8q24 and 9p24 and risk of epithelial ovarian cancer.
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.
Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Kristin L
KL
White
Thomas A
TA
Sellers
Brooke L
BL
Fridley
Robert A
RA
Vierkant
Catherine M
CM
Phelan
Ya-Yu
YY
Tsai
Kimberly R
KR
Kalli
Andrew
A
Berchuck
Edwin S
ES
Iversen
Lynn C
LC
Hartmann
Mark
M
Liebow
Sebastian
S
Armasu
Zachary
Z
Fredericksen
Melissa C
MC
Larson
David
D
Duggan
Fergus J
FJ
Couch
Joellen M
JM
Schildkraut
Julie M
JM
Cunningham
Ellen L
EL
Goode
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D012307:Risk Factors