Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Cao
Yun
Y
The State Key Laboratory of Cancer Biology of Southern China and Department of Experiment, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China. yunsirsums@163.com
Miao
Xiao-Ping
XP
Huang
Ma-Yan
MY
Deng
Ling
L
Hu
Li-Fu
LF
Ernberg
Ingemar
I
Zeng
Yi-Xin
YX
Lin
Dong-Xin
DX
Shao
Jian-Yong
JY
D017677:Age Distribution; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics; D012907:Smoking / Q000009:adverse effects; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human