White Kristin L, Sellers Thomas A, Fridley Brooke L, Vierkant Robert A, Phelan Catherine M, Tsai Ya-Yu, Kalli Kimberly R, Berchuck Andrew, Iversen Edwin S, Hartmann Lynn C, Liebow Mark, Armasu Sebastian, Fredericksen Zachary, Larson Melissa C, Duggan David, Couch Fergus J, Schildkraut Joellen M, Cunningham Julie M, Goode Ellen L
Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Twin Res Hum Genet. 2010 Feb;13(1):43-56. doi: 10.1375/twin.13.1.43.
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.
已知8号染色体q24区域(具体为8q24.21.a)存在与乳腺癌、结直肠癌、前列腺癌和膀胱癌风险相关的变异。2008年,该区域的变异rs10505477和rs6983267与侵袭性卵巢癌风险增加相关(p < 0.01);然而,随后三篇关于8q24变异与卵巢癌关系的报告结果均为阴性。在此,我们开展了一项多中心病例对照研究,纳入940例卵巢癌病例和1041例对照,以评估8q24区域以及9p24结直肠癌相关区域(具体为9p24.1.b)中这些变异及其他单核苷酸多态性(SNP)之间的关联。使用Illumina GoldenGate芯片评估了先前报告中的35个SNP以及额外的标签SNP,并采用逻辑回归模型进行分析,对群体结构和其他潜在混杂因素进行了校正。考虑所有病例、侵袭性病例或侵袭性浆液性病例时,我们未观察到基因型与卵巢癌风险之间存在关联。例如,对于8q24的SNP rs10505477和rs6983267,分析得出每个等位基因的侵袭性癌症优势比分别为0.95(95%置信区间(CI)0.82 - 1.09,p趋势0.46)和0.97(95% CI 0.84 - 1.12,p趋势0.69)。采用与首篇关于8q24的阳性报告相同的方法进行分析,也未发现与卵巢癌风险存在关联。在9p24区域,没有SNP与总体卵巢癌风险、侵袭性或侵袭性浆液性疾病相关(所有p值> 0.10)。这些结果表明,本文研究的SNP与这种妇科恶性肿瘤的风险无关,并且8q24.21.a关联的位点特异性可能不包括卵巢癌。