Moullan Norman, Cox David G, Angèle Sandra, Romestaing Pascale, Gérard Jean-Pierre, Hall Janet
DNA Repair Group, International Agency for Research on Cancer (IARC), Lyon, Cedex, France.
Cancer Epidemiol Biomarkers Prev. 2003 Nov;12(11 Pt 1):1168-74.
The study goal was to examine the association of three polymorphisms in the XRCC1 gene (Arg194Trp, Arg280His, and Arg399Gln) involved in repairing DNA damage produced by ionizing radiation, a known breast cancer (BC) risk factor, with BC incidence and the possibility of developing an adverse radiotherapy response. Genomic DNA from 254 BC cases, 70 of whom were adverse radiotherapy responders [radiation-sensitive breast cancer (RS-BC) patients], and 312 female blood donors were genotyped using either TaqMan technology or variant specific restriction enzyme digestion. Neither the exon 6 codon 194Trp allele [BC versus controls: odds ratio (OR), 1.03; 95% confidence interval (CI) 0.62-1.67] nor the exon 10 codon 399Gln allele (BC versus controls: OR, 0.95; 95% CI, 0.74-1.23) alone was associated with an increased BC risk. The exon 9 codon 280His allele was associated with an increased risk (OR, 1.8; 95% CI, 1.07-3.05) in both the radiation-sensitive and non-radiation-sensitive cases and, in combination with the 399Gln allele, was found more frequently in cases than in controls (OR, 2.54; 95% CI, 1.04-6.22). The exon 6 194Trp allele was associated with the risk of developing an adverse response to radiotherapy (RS-BC versus non-radiation-sensitive BC: OR, 1.98; 95% CI, 0.92-4.17). This allele, in combination with the 399Gln allele, was found more frequently in RS-BC cases than in the non-radiation-sensitive BC cases (OR, 4.33; 95% CI, 1.24-15.12). Distinct combinations of XRCC1 polymorphisms appear to be associated with either an increased BC risk or the possibility of developing an adverse radiotherapy response seen in some BC patients.
本研究的目的是探讨参与修复由电离辐射产生的DNA损伤的XRCC1基因中的三种多态性（Arg194Trp、Arg280His和Arg399Gln）与乳腺癌（BC）发病率以及出现放疗不良反应可能性之间的关联。已知电离辐射是乳腺癌的一个风险因素。采用TaqMan技术或变异特异性限制性内切酶消化法，对254例乳腺癌病例（其中70例为放疗不良反应者，即辐射敏感型乳腺癌（RS-BC）患者）以及312名女性献血者的基因组DNA进行基因分型。单独的外显子6密码子194Trp等位基因（乳腺癌与对照组：比值比（OR），1.03；95%置信区间（CI）0.62 - 1.67）和外显子10密码子399Gln等位基因（乳腺癌与对照组：OR，0.95；95% CI，0.74 - 1.23）均与乳腺癌风险增加无关。外显子9密码子280His等位基因在辐射敏感型和非辐射敏感型病例中均与风险增加相关（OR，1.8；95% CI，1.07 - 3.05），并且与399Gln等位基因组合时，在病例组中比对照组中更常见（OR，2.54；95% CI，1.04 - 6.22）。外显子6 194Trp等位基因与放疗不良反应风险相关（RS-BC与非辐射敏感型BC：OR，1.98；95% CI，0.92 - 4.17）。该等位基因与399Gln等位基因组合时，在RS-BC病例中比非辐射敏感型BC病例中更常见（OR，4.33；95% CI，1.24 - 15.12）。XRCC1基因多态性的不同组合似乎与某些乳腺癌患者中乳腺癌风险增加或出现放疗不良反应的可能性相关。
