Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set
Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: Results from two Australian studies and an additional validation set
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DOI：
10.1158/1055-9965.epi-07-0542
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发表时间：
2007-12-01
影响因子：
3.8
通讯作者：
Chenevix-Trench, Georgia
中科院分区：
文献类型：
--
作者：
Beesley, Jonathan;Jordan, Susan J.;Chenevix-Trench, Georgia
虽然一些高风险的卵巢癌基因已被确定，它可能是常见的低等位基因存在，赋予卵巢癌的风险增加。我们使用两项澳大利亚卵巢癌病例对照研究对参与类固醇激素合成（SRD 5A 2、CYP 19 A1、HSB 17 B1和HSD 17 B4）和DNA修复（XRCC 2、XRCC 3、BRCA 2和RAD 52）的基因中的9个推定功能性单核苷酸多态性（SNP）进行了基因分型，共包括1，466例白人病例和1，821例白人对照。病例组和对照组的基因型频率采用Logistic回归进行比较。在这两项研究中，我们发现与卵巢癌风险相关的唯一SNP是SRD 5A 2 V89 L（rs 523349），其显示每个罕见等位基因的风险增加趋势显著（P = 0.00002）。然后，我们对该基因的另一个SNP进行了基因分型（rs632148; r（2）= 0.945与V89 L），试图在来自英国、美国和丹麦的1，479例病例和2，452例对照的独立组中验证这一发现。在验证样本中，rs632148与卵巢癌风险之间没有关联，总体而言，五项研究的结果之间没有显著的异质性。因此，有必要对该基因中的SNP进行进一步分析，以确定SRD 5A 2是否在卵巢癌易感性中发挥作用。
Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then 2 genotyped another SNP in this gene (rs632148; r(2) = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition.