Cao Yun, Miao Xiao-Ping, Huang Ma-Yan, Deng Ling, Hu Li-Fu, Ernberg Ingemar, Zeng Yi-Xin, Lin Dong-Xin, Shao Jian-Yong
The State Key Laboratory of Cancer Biology of Southern China and Department of Experiment, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
BMC Cancer. 2006 Jun 26;6:167. doi: 10.1186/1471-2407-6-167.
Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and diet, genetic susceptibility has been reported to play a key role in the development of this disease. The x-ray repair cross-complementing group 1 (XRCC1) gene is important in DNA base excision repair. We hypothesized that two common single nucleotide polymorphisms of XRCC1 (codons 194 Arg-->Trp and 399 Arg-->Gln) are related to the risk of NPC and interact with tobacco smoking.
We sought to determine whether these genetic variants of the XRCC1 gene were associated with the risk of NPC among the Cantonese population in a hospital-based case control study using polymerase chain reaction-restriction fragment length polymorphism analysis. We conducted this study in 462 NPC patients and 511 healthy controls.
After adjustment for sex and age, we found a reduced risk of developing NPC in individuals with the Trp194Trp genotype (OR = 0.48; 95% CI, 0.27-0.86) and the Arg194Trp genotype (OR = 0.79; 95% CI, 0.60-1.05) compared with those with the Arg194Arg genotype. Compared with those with the Arg399Arg genotype, the risk for NPC was not significantly different in individuals with the Arg399Gln genotype (OR = 0.82; 95% CI, 0.62-1.08) and the Gln399Gln genotype (OR = 1.20; 95% CI, 0.69-2.06). Further analyses stratified by gender and smoking status revealed a significantly reduced risk of NPC among males (OR = 0.32; 95% CI, 0.14-0.70) and smokers (OR = 0.34; 95% CI, 0.14-0.82) carrying the XRCC1 194Trp/Trp genotype compared with those carrying the Arg/Arg genotype. No association was observed between Arg399Gln variant genotypes and the risk of NPC combined with smoking and gender.
Our findings suggest that the XRCC1 Trp194Trp variant genotype is associated with a reduced risk of developing NPC in Cantonese population, particularly in males and smokers. Larger studies are needed to confirm our findings and unravel the underlying mechanisms.
鼻咽癌（NPC）是中国南方最常见的癌症之一。除了诸如爱泼斯坦-巴尔病毒感染和饮食等环境因素外，遗传易感性据报道在该疾病的发生发展中起关键作用。X射线修复交叉互补基因1（XRCC1）在DNA碱基切除修复中很重要。我们假设XRCC1的两个常见单核苷酸多态性（密码子194 Arg→Trp和399 Arg→Gln）与鼻咽癌风险相关，并与吸烟存在相互作用。
在一项基于医院的病例对照研究中，我们试图通过聚合酶链反应-限制性片段长度多态性分析来确定XRCC1基因的这些遗传变异是否与粤语人群中的鼻咽癌风险相关。我们对462例鼻咽癌患者和511例健康对照进行了这项研究。
在对性别和年龄进行调整后，我们发现与携带Arg194Arg基因型的个体相比，携带Trp194Trp基因型（OR = 0.48；95%CI，0.27 - 0.86）和Arg194Trp基因型（OR = 0.79；95%CI，0.60 - 1.05）的个体患鼻咽癌的风险降低。与携带Arg399Arg基因型的个体相比，携带Arg399Gln基因型（OR = 0.82；95%CI，0.62 - 1.08）和Gln399Gln基因型（OR = 1.20；95%CI，0.69 - 2.06）的个体患鼻咽癌的风险无显著差异。按性别和吸烟状况分层的进一步分析显示，与携带Arg/Arg基因型的个体相比，携带XRCC1 194Trp/Trp基因型的男性（OR = 0.32；95%CI，0.14 - 0.70）和吸烟者（OR = 0.34；95%CI，0.14 - 0.82）患鼻咽癌的风险显著降低。未观察到Arg399Gln变异基因型与结合吸烟和性别的鼻咽癌风险之间存在关联。
我们的研究结果表明，XRCC1 Trp194Trp变异基因型与粤语人群中患鼻咽癌风险降低相关，尤其是在男性和吸烟者中。需要更大规模的研究来证实我们的发现并阐明潜在机制。
