1.
Association between XRCC1 Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk in Asian population.
Wu, D, Jiang, H, Gu, Q, Zhang, D, Li, Z
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2013;(5):3265-9
Abstract
To investigate the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk, we performed a systematic meta-analysis of eligible case-control studies. Eligible studies were identified from the PubMed, Embase, and Chinese National Knowledge Infrastructure databases up to March 2013. The odds ratios (ORs) and corresponding 95 % confidence interval (95 % CI) of XRCC1 Arg399Gln polymorphism in hepatitis virus-related hepatocellular carcinoma cases compared with those in controls were calculated. The meta-analysis was performed using fixed-effect or random-effect methods according to the absence or presence of heterogeneity. This meta-analysis included 1,558 cases with hepatitis virus-related hepatocellular carcinoma and 1,338 controls. Meta-analysis of available data showed that there was no association between XRCC1 Arg399Gln polymorphism and risk of hepatitis virus-related hepatocellular carcinoma under all contrast models (Gln vs. Arg: fixed-effect OR = 0.92, 95 % CI 0.82-1.04, P = 0.18; GlnGln vs. ArgArg: random-effect OR = 0.79, 95 % CI 0.50-1.25, P = 0.32; GlnGln/ArgGln vs. ArgArg: fixed-effect OR = 0.92, 95 % CI 0.79-1.07, P = 0.28; and GlnGln vs. ArgArg/ArgGln: random-effect OR = 0.83, 95 % CI 0.52-1.34, P = 0.45). Sensitivity analysis further showed that there was no association between XRCC1 Arg399Gln polymorphism and risk of hepatitis B-related hepatocellular carcinoma under all contrast models (Gln vs. Arg: fixed-effect OR = 0.93, 95 % CI 0.82-1.05, P = 0.25; GlnGln vs. ArgArg: fixed-effect OR = 0.86, 95 % CI 0.64-1.16, P = 0.32; GlnGln/ArgGln vs. ArgArg: fixed-effect OR = 0.93, 95 % CI 0.80-1.10, P = 0.41; and GlnGln vs. ArgArg/ArgGln: fixed-effect OR = 0.85, 95 % CI 0.63-1.13, P = 0.26). Our meta-analysis of the available data did not find an obvious effect of XRCC1 Arg399Gln polymorphism on hepatitis-related hepatocellular carcinoma. More well-designed studies with large sample are needed to further verify the effect.
2.
Genetic polymorphism of XRCC1 correlated with response to oxaliplatin-based chemotherapy in advanced colorectal cancer.
Lv, H, Li, Q, Qiu, W, Xiang, J, Wei, H, Liang, H, Sui, A, Liang, J
Cancer investigation. 2013;(1):24-8
Abstract
In this study, we investigated the association between genetic polymorphisms of XRCC1 Arg399Gln (G→A) and response to oxaliplatin-based chemotherapy in advanced colorectal cancer. XRCC1 genotypes of totally 99 patients (37 stage III and 62 stage IV) with advanced colorectal cancer treated with oxaliplatin-based chemotherapy were detected by the TaqMan-MGB probe allelic discrimination method, and clinical response of 62 patients in stage IV after 2 to 3 cycles of chemotherapy were evaluated. Also, time to progression (TTP) of all patients was evaluated. The results showed that of the genotype frequencies in all patients, up to 52.53% were G/G genotype, 9.09% were A/A genotype, and 38.38% were G/A genotype. The response rate (CR + PR) of 62 patients in stage IV was 61.29% (19/31). Patients with G/G genotype showed enhanced response to chemotherapy compared with those with G/A + A/A (x(2) = 5.6, p = .029; Odds Ratio (OR) = 3.845, 95% Confidence Interval (CI) = 1.231 ∼ 12.01, p = .018). Individuals with the G/G genotype had a TTP of 10.0 (8.88-11.12) months, and those with the G/A + A/A genotype had a TTP of 5.0 (4.26-5.74) months. The Log-Rank test was marginally significant (x(2) = 29.20, p < .01). The Cox proportional hazards model, adjusted for stage, performance status, and chemotherapy regimen showed that only XRCC1 G/G genotype increases the OR significantly (OR = 3.555; 95% CI, 2.119 ∼ 5.963; p < .01). These results indicate that XRCC1 Arg399Gln polymorphism is associated with response to oxaliplantin-based chemotherapy and TTP in advanced colorectal cancer in Chinese population. It is proposed that the XRCC1 Arg399Gln polymorphism should be routinely detected to screen patients who are more likely to benefit from oxaliplantin-based treatment.