Auranen Annika, Song Honglin, Waterfall Christy, Dicioccio Richard A, Kuschel Bettina, Kjaer Susanne K, Hogdall Estrid, Hogdall Claus, Stratton John, Whittemore Alice S, Easton Douglas F, Ponder Bruce A J, Novik Karen L, Dunning Alison M, Gayther Simon, Pharoah Paul D P
CR-UK Department of Oncology, University of Cambridge, Strangeways Research Laboratory.
Int J Cancer. 2005 Nov 20;117(4):611-8. doi: 10.1002/ijc.21047.
DNA repair gene polymorphisms and mutations are known to influence cancer risk. We studied whether polymorphisms in DNA double strand break (DSB) repair genes are associated with epithelial ovarian cancer (EOC) risk. Up to 1,600 cases and 4,241 controls from 4 separate genetic association studies from 3 countries were genotyped for 13 single nucleotide polymorphisms (SNP) in 6 genes (BRCA1, NBS1, RAD51, RAD52, XRCC2 and XRCC3) involved in homologous recombination of DNA double strand breaks. Genotype specific risks were estimated as odds ratios (OR) by unconditional logistic regression. No association was detected between EOC risk and BRCA1 Q356R, BRCA1 P871L, RAD51 g135c, RAD51 g172t, RAD52 c2259t, NBS1 L34L, NBS1 E185Q, NBS1 A399A, NBS1 P672P, XRCC2 g4324c, XRCC2 c41657t and XRCC3 T241M. The XRCC2 R188H polymorphism was associated with a modest reduction in EOC risk: OR for heterozygotes was 0.8 (95% confidence interval [CI] = 0.7-1.0) and for rare homozygotes 0.3 (0.1-0.9). The XRCC3 a4541g polymorphism, situated in the 5'UTR, and the intronic XRCC3 a17893g polymorphism were not associated with EOC risk in general, but when the serous EOC subset only was analysed, the OR for heterozygotes for a4541g was 1.0 (0.9-1.2) and for the rare homozygotes 0.5 (0.3-0.9). For the XRCC3 a17893g polymorphism, the OR for the heterozygotes and the rare homozygotes were 0.8 (0.7-0.9) and 0.9 (0.7-1.2), respectively. In our study, some polymorphisms in XRCC2 and XRCC3 genes were associated with EOC risk. Further research on the role of these genes on epithelial ovarian cancer is warranted.
已知DNA修复基因多态性和突变会影响癌症风险。我们研究了DNA双链断裂（DSB）修复基因中的多态性是否与上皮性卵巢癌（EOC）风险相关。对来自3个国家的4项独立基因关联研究中的多达1600例病例和4241例对照，进行了参与DNA双链断裂同源重组的6个基因（BRCA1、NBS1、RAD51、RAD52、XRCC2和XRCC3）中13个单核苷酸多态性（SNP）的基因分型。通过无条件逻辑回归将基因型特异性风险估计为比值比（OR）。未检测到EOC风险与BRCA1 Q356R、BRCA1 P871L、RAD51 g135c、RAD51 g172t、RAD52 c2259t、NBS1 L34L、NBS1 E185Q、NBS1 A399A、NBS1 P672P、XRCC2 g4324c、XRCC2 c41657t和XRCC3 T241M之间存在关联。XRCC2 R188H多态性与EOC风险适度降低相关：杂合子的OR为0.8（95%置信区间[CI]=0.7-1.0），罕见纯合子的OR为0.3（0.1-0.9）。位于5'UTR的XRCC3 a4541g多态性和内含子XRCC3 a17893g多态性一般与EOC风险无关，但仅分析浆液性EOC亚组时，a4541g杂合子的OR为1.0（0.9-1.2），罕见纯合子的OR为0.5（0.3-0.9）。对于XRCC3 a17893g多态性，杂合子和罕见纯合子的OR分别为0.8（0.7-0.9）和0.9（0.7-1.2）。在我们的研究中，XRCC2和XRCC3基因中的一些多态性与EOC风险相关。有必要对这些基因在上皮性卵巢癌中的作用进行进一步研究。
