Costa Sandra, Pinto Daniela, Pereira Deolinda, Rodrigues Helena, Cameselle-Teijeiro Jorge, Medeiros Rui, Schmitt Fernando
ICVS, Life and Health Sciences Research Institute, Health Science School, Minho University, Braga, 4710-057, Portugal.
Breast Cancer Res Treat. 2007 Jun;103(2):209-17. doi: 10.1007/s10549-006-9364-z. Epub 2006 Oct 25.
The purpose of this study was to evaluate the role of polymorphisms in DNA repair genes as genetic indicators of susceptibility to familial and sporadic breast cancer. We analysed DNA samples from 285 breast cancer patients and 442 control subjects, for XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met polymorphisms using PCR-RFLP. We observed that women carriers of XRCC1 399Gln genotypes and without family history of breast cancer have a protective effect concerning this disease (OR = 0.54 95% CI 0.35-0.84; p = 0.006). Furthermore, we found that carriers of XRCC3 241Met genotypes without FH have an increased susceptibility of breast cancer (OR = 2.21 95% CI 1.42-3.44; p < 0.001). Additionally, we verified an increased risk of breast cancer in women with FH and carrying RAD51 135C genotypes (OR = 2.17 95% CI 1.19-3.98; p = 0.012). Our results suggest XRCC1 Arg399Gln and XRCC3 Thr241Met DNA repair polymorphisms as important biomarkers to sporadic breast cancer susceptibility, as well as, RAD51 G135C polymorphism as a real risk modifier in familial breast cancer cases.
本研究的目的是评估DNA修复基因多态性作为家族性和散发性乳腺癌易感性遗传指标的作用。我们使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析了285例乳腺癌患者和442例对照受试者的DNA样本，检测XRCC1基因的Arg399Gln、XPD基因的Lys751Gln、RAD51基因的G135C以及XRCC3基因的Thr241Met多态性。我们观察到，携带XRCC1基因399Gln基因型且无乳腺癌家族史的女性对该疾病具有保护作用（比值比=0.54，95%置信区间0.35-0.84；p=0.006）。此外，我们发现携带XRCC3基因241Met基因型且无家族史的个体患乳腺癌的易感性增加（比值比=2.21，95%置信区间1.42-3.44；p<0.001）。另外，我们证实有家族史且携带RAD51基因135C基因型的女性患乳腺癌的风险增加（比值比=2.17，95%置信区间1.19-3.98；p=0.012）。我们的结果表明，XRCC1基因的Arg399Gln和XRCC3基因的Thr241Met DNA修复多态性是散发性乳腺癌易感性的重要生物标志物，而RAD51基因的G135C多态性是家族性乳腺癌病例中真正的风险修饰因子。
