In addition, the Arg194Trp</span> vari</span>ant reduced the risk of lung cancer associated with increased serum carotenoids compared to those with the homozygous wild-type allele.
To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genes with lung cancer risk in northeastern Chinese.
Hence, we performed a meta-analysis to investigate the association between lung cancer risk and XRCC1 Arg399Gln (14,156 cases and 16,667 controls from 41 studies), Arg194Trp (7,426 cases and 9,603 controls from 23 studies), Arg280His (6,211 cases and 6,763 controls from 16 studies), -77T>C (2,487 cases and 2,576 controls from 5 studies), and XRCC3 T241M (8,560 cases and 11,557 controls from 19 studies) in different inheritance models.
To establish our understanding of possible relationships between XRCC1 polymorphisms (5'UTR -77T>C, Arg194Trp, Arg280His and Arg399Gln) and the susceptibility to lung cancer among women nonsmokers, we performed a hospital-based case-control study of 350 patients with newly diagnosed lung cancer and 350 cancer-free controls, frequency matched by age.
Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype.
In the subgroup analysis by cancer sites, the Arg194Trp polymorphism was associated with increased risks of lung cancer (OR = 1.27 and 95%CI: 1.07-1.50 for Trp/Trp versus Arg/Arg + Arg/Trp) and esophageal cancer (OR = 1.68 and 95%CI: 1.33-2.13 for Trp/Trp versus Arg/Arg + Arg/Trp).
The result involving 8,876 lung cancer patients and 11,210 controls revealed that XRCC1 Arg194Trp polymorphism was not associated with lung cancer risk [(OR=0.97, 95 %CI=0.92-1.03) for Trp vs. Arg; (OR=0.92, 95 % CI=0.85-0.98) for ArgTrp vs. ArgArg; (OR=1.07, 95 % CI=0.92-1.23) for TrpTrp vs. ArgArg; (OR=0.93, 95 % CI=0.87-1.00) for (TrpTrp + ArgTrp) vs. ArgArg; and (OR=1.08, 95 % CI=0.94-1.25) for TrpTrp vs. (ArgTrp + ArgArg)].
Additionally, four polymorphisms of XRCC1 (rs25487, rs25489, rs1799782, and rs3213245), which were investigated with regard to their association with lung cancer risk in previous studies, were also genotyped.
The associations between the OGG1 Cys/Cys genotype and adenocarcinoma risk and between XRCC1 Arg194Trp</span> polymorphism and lung cancer risk among heavy smokers remained robust given prior probabilities of 25% (FPRP = 0.238) and 10% (FPRP = 0.276), respectively.
We found decreased lung cancer risk among subjects carrying XRCC1 codon 194 Arg/Trp genotype [odds ratio (OR)=0.88, 95% confidence interval (95% CI): 0.79-0.97], using 4848 cases and 6592 controls from 16 studies.
Our meta-analysis on 2861 cases (lung cancer patients) and 2783 controls from eight eligible studies in Chinese populations showed that for the XRCC1 Arg194Trp polymorphism, compared with the Arg/Arg homozygous genotype, the variant Arg/Trp and Trp/Trp genotypes combined was not associated with lung cancer risk (OR=1.06, 95% confidence interval [CI]=0.89-1.27) (Z=0.70, P=0.48), nor was Arg280His (OR=0.63, 95% CI=0.28-1.41) (Z=1.12, P=0.26); however, for the XRCC1 Arg399Gln polymorphism, the combination of variant Arg/Gln and Gln/Gln genotypes was borderline significantly associated with lung cancer risk (OR=1.16, 95% CI=1.00-1.36) (Z=1.90, P=0.06), compared with the Arg/Arg homozygous genotype.
When stratified by source of control, we found a protective effect of codon 194 Arg/Trp genotype (OR: 0.87; 95 % CI 0.77-0.98) and risk effect of codon 399 combined Arg/Gln + Gln/Gln variant genotype (OR: 1.09; 95 % CI 1.01-1.18) for lung cancer on the basis of hospital control.
In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.
These findings further suggest that the polymorphisms XRCC1 Arg194Trp and Pro206Pro or the haplotype encompassing the variant alleles may contribute to susceptibility of lung cancer in a Chinese population.
However, there was no obvious association between XRCC1 Arg</span>194Trp polymorphism and lung cancer risk under the dominant model (OR = 1.06, 95 % CI 0.98-1.16, P = 0.146).
In summary, this meta-analysis suggests that Arg194Trp polymorphism may be associated with increased breast cancer risk, Arg194Trp polymorphism is associated with increased glioma risk among Asians, and Arg194Trp polymorphism is associated with decreased lung cancer risk among Caucasians.
Both the XRCC1 Arg194Trp and Arg280His as well as the OGG1 Ser326Cys heterozygous genotypes were associated with a significantly reduced risk for lung cancer (OR=0.32, p=0.024; OR=0.25, p=0.028; OR=0.51, p=0.033, respectively).