• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.111-115
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• 2012

Variants of X-ray repair cross-complementing group 1 (XRCC1) are involved in the development of cancer, but studies investigating the association of XRCC1-77T>C polymorphism with cancer risk have reported conflicting results. To clarify the effect of the XRCC1 -77T>C polymorphism on cancer risk, we performed a meta-analysis by conducting searches of the published literature in PubMed, Embase and CBM databases. Finally, 13 studies were included into our meta-analysis, involving a total of 11, 678 individuals. Subgroup analyses were performed by ethnicity and cancer type. The results of this meta-analysis showed that there was significant association between the C variant of XRCC1-77T>C polymorphism and cancer risk in all four genetic comparison models (ORC vs. T =1.19, 95%CI 1.07-1.31, P = 0.001; OR homozygote model =1.28, 95%CI 1.07-1.52, P = 0.007; OR recessive genetic model =1.22, 95%CI 1.04-1.44, P = 0.015; OR dominant model =1.21, 95% CI 1.07-1.35, P = 0.001). In the subgroup analyses based on ethnicity, the association was still significant in the Asian population (all p values<0.001), but not in the Caucasian population (all p values > 0.05). Thus, the XRCC1 -77T>C polymorphism is associated with cancer risk, and individuals with XRCC1 -77C variant have a significantly higher cancer risk, particularly in the Asian population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10225-10229
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• 2015

Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6613-6618
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• 2014

Background: The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. Attention has been drawn upon associations of the XRCC3 Thr241Met polymorphism with breast cancer risk. However, the previous published findings remain controversial. Hence, we performed a meta-analysis to accurately evaluate any association between breast cancer and XRCC3 T241M (23, 812 cases and 25, 349 controls) in different inheritance models. Materials and Methods: PubMed and Web of Science databases were searched systematically until December 31, 2013 to obtain all the records evaluating the association between the XRCC3 Thr241Met polymorphism and breast cancer risk. Crude odds ratios (ORs) together with 95% confidence intervals (CIs) were used to assess the strength of associations. Results: When all eligible studies were pooled into the meta analysis of XRCC3 T241M polymorphism, a significantly increased breast cancer risk was observed in heterozygote comparison (OR=1.06, 95%CI=1.01-1.12). No significant associations were found in other models. In subgroup analysis, this polymorphism seemed to be associated with elevated breast risk in Asians. No publication bias was detected. Conclusions: This meta-analysis suggests that the T241M polymorphism confers a weakly increased breast cancer risk. A study with the larger sample size is needed to further evaluate gene-gene and gene-environment interactions of the XRCC3 T241M polymorphism with breast cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4599-4608
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• 2016

Background: The x-ray repair cross-complementing group 3 (XRCC3) encodes a protein involved in the homologous recombination repair (HRR) pathway for double-strand DNA repair. Associations of the XRCC3 Thr241Met polymorphism with various cancers have been widely reported. However, published data on links between XRCC3 Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. Objective and Methods: A meta-analysis was conducted to characterize the relationship between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooled odds ratios (ORs) and 95.0% confidence intervals were assessed using random- or fixed- effect models for 28.0 relevant articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls. Results: The results of the overall meta-analysis suggested a borderline association between the XRCC3 Thr241Met polymorphism and GI cancer susceptibility (T vs. C: OR=1.18, 9 % CI=1.0-1.4, POR=0.04; TT vs. CT+CC: OR=1.3, 95 % CI=1.0-1.6, POR=0.04). After removing studies not conforming to Hardy-Weinberg equilibrium (HWE), however, this association disappeared (T vs. C: OR=1.00, 95 % CI=0.9-1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8-1.1, POR=0.72). When stratified by ethnicity, source of controls or cancer type, although some associations between XRCC3 Thr241Met polymorphism and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming to HWE. Conclusion: Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with risk of GI cancer based on current evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4095-4099
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• 2014

The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA base excision repair pathway which may influence the development of lung cancer. This study aimed to evaluate the potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluate the XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associations between the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regression model. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantly different from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increased risk of lung cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22-1.90, p<0.001). The allele A and genotype AA may contribute to risk of lung cancer. These preliminary results suggested that the XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6385-6390
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• 2015

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Materials and Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Results: Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p < 0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. Conclusions: Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3169-3173
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• 2013

Background: Findings from previous published studies regarding the association of the XRCC3 Thr241Met polymorphism with glioma susceptibility have often been conflicting. Therefore, a meta-analysis including all available publications was carried out to make a more precise estimation of the potential relationship. Methods: By searching the electronic databases of Pubmed and Embase (up to April 1st, 2013), a total of nine case-control studies with 3,752 cases and 4,849 controls could be identified for inclusion in the current meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. Results: This meta-analysis showed the XRCC3 Thr241Met polymorphism to be significantly associated with decreased glioma risk in the allelic model (Met allele vs. Thr allele: OR= 0.708, 95%CI= 0.631-0.795). Moreover, we also observed a statistically significant association between the XRCC3 Thr241Met polymorphism and reduced glioma risk in analyses stratified by ethnicity (Asian) and source of controls (hospital based) in the allelic model. Conclusions: Current evidence suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for glioma development, especially in Asians.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3285-3291
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• 2015

Background: Non-synonymous polymorphisms in XRCC1 hase been shown to reduce effectiveness of DNA repair and be associated with risk of certain cancers. In this study we aimed to clarify any association between XRCC1 Arg399Gln and colorectal cancer (CRC) risk by performing a meta-analysis of published case-control studies. Materials and Methods: PubMed and Google Scholar were searched to explore the association between XRCC1 and CRC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias was assessed by Egger's and Begg's tests. Results: Up to January 2015, 35 case control studies involving 9,114 CRC cases and 13,948 controls were included in the present meta-analysis. The results showed that the Arg399Gln polymorphism only under an allele genetic model was associated with CRC risk (A vs. G: OR 0.128, 95% CI 0.119-0.138, p<0.001). Also, this meta-analysis suggested that the XRCC1 Arg399Gln polymorphism might associated with susceptibility to CRC in Asians (A vs G: OR 0.124, 95% CI 0.112-0.138, p<0.001) and Caucasian (A vs G: OR 0.132, 95% CI 0.119-0.146, p<0.001) only under an allele genetic model. Conclusions: This meta-analysis confirms the association between XRCC1 Arg399Gln polymorphism and CRC risk and suggests that the heterogeneity is not strongly modified by ethnicity and deviation from the Hardy-Weinberg equilibrium.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6385-6390
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• 2012

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.191-194
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• 2012

We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. A total of 150 cases and 158 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. A significantly increased risk was associated with the Arg/Gln genotype (adjusted OR 1.78, 95%CI=1.13-2.79) compared with genotype Arg/Arg. In contrast, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.69 (0.93-2.66). A significant association was found between positive HBsAg and Arg/Gln, with an OR of 3.43 (95% CI=1.45-8.13). Patients carrying Gln/Gln genotypes showed significantly lower median survival than Arg/Arg genotypes (HR=1.38, 95% CI=1.04-1.84). Further Kaplan-Meier analysis showed decreased median survival in Arg/Gln+Gln/Gln genotype carriers in comparison to Arg/Arg carriers (HR=1.33, 95% CI=1.02-1.76). In conclusion, we observed that XRCC1-Arg399Cln polymorphism is associated with susceptibility to HCC, and XRCC1 Gln allele genotype showed significant prognostic associations.