Comprehensive assessment of the association between DNA repair gene XRCC3 Thr241Met polymorphism and leukemia risk

The XRCC3 gene has been suggested to play an important role in the pathogenesis of leukemia risk. But the findings of publications are contradictory. To derive a more precise estimation of the association, we performed a meta-analysis. The PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched for case–control studies published up to August 2013. The pooled odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated by using a fixed- or random-effect model. A total of 15 case–control studies met the inclusion criteria and were selected. The pooled OR showed that there was no statistically significant association between XRCC3 Thr241Met polymorphism and leukemia risk in overall including studies, while a risky association was observed for acute myeloid leukemia (AML) (dominant model TT/TC vs. CC: OR = 1.240, 95 % CI = 1.018–1.511, P = 0.032). The XRCC3 Thr241Met polymorphism might be associated with risk of leukemia in AML. More studies with larger sample sizes are needed to validate this result.     

DNA repair gene XRCC3 Thr241Met polymorphism and hepatocellular carcinoma risk

The DNA repair genes have been indicated as candidates in the risk of hepatocellular carcinoma (HCC). Published data on the association between X-ray repair cross-complementing group 3 (XRCC3), a critical member of the DNA repair genes, and HCC risk were contradictory. The aim of this meta-analysis was to assess the effect of XRCC3 Thr241Met polymorphism on HCC risk by pooling available data from published case–control studies. We calculated the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) to estimate the effect. Based on the inclusion criteria, six individual studies with 2,288 cases and 3,170 controls were included into our study. Overall, significant association between the XRCC3 Thr241Met variant and HCC risk was observed under the following contrast models (OR_{Met vs. Thr}?=?1.68, 95 %CI 1.08–2.62; OR_{MetMet vs. ThrThr}?=?5.54, 95 %CI 3.09–9.94; OR_{MetMet vs. ThrThr?+?ThrMet}?=?5.70, 95 % CI 4.24–7.64). Besides, the pooled ORs indicated that the XRCC3 Thr241Met polymorphism exerted risk effect on the HCC pathogenesis among Asians. Additionally, when stratifying by the status of smoking and hepatitis B virus infection, the XRCC3 Thr241Met variant was significantly associated with HCC risk among the HBsAg (+) individuals but not the HBsAg (?) individuals, smokers, and non-smokers. The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism is an independent risk factor for HCC, particularly among Asians and the HBsAg (+) individuals.     

Comprehensive assessment of the association between DNA repair gene XRCC3 rs861539 C/T polymorphism and lung cancer risk

A few case–control studies were performed to assess the association between X-ray repair cross-complementing group 3 (XRCC3) rs861539 C/T polymorphism and lung cancer susceptibility, but no consistent finding was reported. In the present study, we performed a meta-analysis of 14 case–control studies with a total of 7,869 lung cancer cases and 10,778 controls to provide a comprehensive assessment of the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Overall, there was no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models [OR (95 % CI) for T versus C, 1.00 (0.89–1.13), P?=?0.99; OR (95 % CI) for TT versus CC, 1.07 (0.81–1.41), P?=?0.62; OR (95 % CI) for TT/CT versus CC, 0.95 (0.84–1.07), P?=?0.39; OR (95 % CI) for TT versus CT/CC, 1.10 (0.86–1.39), P?=?0.62]. In the subgroup analyses of both Asians and Caucasians, there was still no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models (All P values were more than 0.05). However, there was an obvious association between XRCC3 rs861539 C/T polymorphism and decreased risk of lung cancer in the subgroup analysis of the mixed population (All P values were less than 0.05). In addition, there was some risk of publication bias in the meta-analysis, and there was obvious discrepancy in the findings between studies with large sample size and studies with small sample size in the meta-analysis. The meta-analysis indicates that the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk is still uncertain owing to the obvious discrepancy in the findings between studies with large sample size and studies with small sample size. More studies with large sample size are needed to further assess the association.     

No significant association between the XRCC3 Thr241Met polymorphism and lung cancer risk: a meta-analysis

The development of lung cancer is significantly associated with genetic susceptibility. Findings from previous individual studies regarding the effect of X-ray repair cross-complementing group 3 Thr241Met (XRCC3 Thr241Met) polymorphism on lung cancer risk remained conflicting and inconclusive. Thus, a meta-analysis of previous relevant studies was performed to estimate this effect more precisely and to shed some light on the contradictory findings. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the correlation of XRCC3 Thr241Met polymorphism with lung cancer susceptibility. Stratified analysis according to ethnicity and sensitivity analysis was both conducted for further confirmation. Seventeen independent case–control studies involving 12,610 subjects totally were included into this meta-analysis. Overall, meta-analysis of total included studies showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (OR_{Met allele vs. Thr allele}?=?1.01, 95 % CI 0.91–1.13, P _OR?=?0.810; OR_{Met/Met vs. Thr/Thr}?=?1.16, 95 % CI 0.88–1.54, P _OR?=?0.281; OR_{Thr/Met vs. Thr/Thr}?=?0.95, 95 % CI 0.86–1.04, P _OR?=?0.240; OR_{Met/Met?+?Thr/Met vs. Thr/Thr}?=?0.97, 95 % CI 0.89–1.06, P _OR?=?0.538; OR_{Met/Met vs. Thr/Thr?+?Thr/Met}?=?1.18, 95 % CI 0.91–1.52, P _OR?=?0.204). Stratified analyses in Asians and Caucasians showed similar results. Sensitivity analysis confirmed the stability and reliability of the findings. This meta-analysis of all available data did not support any appreciable association between the XRCC3 Thr241Met polymorphism and lung cancer risk in any populations.     

DNA损伤修复基因XRCC3 Thr241Met多态与肺癌易感性关系的Meta分析

目的:探讨DNA损伤修复基因X射线交叉互补修复基因3(XRCC3)Thr241Met多态性与肺癌易感性的关系。方法:查找中国医学文献数据库和PubMed,以得到XRCC3基因Thr241Met多态与肺癌易感性关系的病例-对照研究,根据纳入和排除标准筛选符合条件的研究进行Meta分析,合并XRCC3基因Thr241Met多态与肺癌易感性关系的OR值,然后进行亚组分析、敏感性分析和文献的发表偏倚检验。结果:本次Meta分析共纳入13篇文献,累计病例2 986例,对照4 495例,显性模型下TM+MM基因型相对于TT(TM=Thr/Met)基因型OR值为0.96(95%CI为0.86~1.06),差异无统计学意义。结论:尚无足够证据证明XRCC3基因Thr241Met多态同肺癌易感性有关。     

Association between XRCC3 T241M polymorphism and glioma risk: a meta-analysis

X-ray repair cross-complementing group 3 (XRCC3) plays a critical role in homologous recombination repair (HRR) accounting for repair of DNA double-strand breaks (DSB). Attention has been drawn upon the association of XRCC3 T241M polymorphism with glioma risk. The present meta-analysis aimed to examine whether XRCC3 T241M polymorphism was associated with glioma risk. Eligible articles were identified for the period up to March 2013. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were appropriately derived from fixed effects or random effects models. Eight case-control studies with a total of 3,455 glioma cases and 4,435 controls were included. Overall, no significant association between XRCC3 T241M polymorphism and glioma was found. In subgroup analysis, this polymorphism seemed to be associated with elevated glioma risk in Asians. No publication bias was detected. This meta-analysis suggested that XRCC3 T241M polymorphism did not confer glioma risk.     

Quantitative assessment of the associations between DNA repair gene XRCC3 Thr241Met polymorphism and gastric cancer

Gastric cancer is one of the most prevalent types of cancer in the world today. Recently, there is a large sample volume of published case–control studies on XRCC3 Thr241Met polymorphism with gastric cancer. This will have an important impact on published article by meta-analysis regarding XRCC3 Thr241Met polymorphism with gastric cancer. Therefore, it is necessary to update by meta-analysis to comprehensively investigate the relationship between DNA repair gene XRCC3 Thr241Met polymorphism and gastric cancer. To preciously examine the association between the XRCC3 Thr241Met polymorphism and gastric cancer, we undertook a meta-analysis of 12 case–control studies. The association between the XRCC3 Thr241Met polymorphism and gastric cancer risk was assessed by odds ratios together with their 95 % confidence intervals using a fixed-effects model or random-effects model. We found that the XRCC3 Thr241Met polymorphism was not associated with an increased gastric cancer risk. However, the XRCC3 Thr241Met polymorphism was associated with decreased gastric cancer risk in Asians. In addition, there is no evidence of association on XRCC3 Thr241Met polymorphism with response to chemotherapy and prognosis in gastric cancer. The XRCC3 Thr241Met polymorphism might influence gastric cancer risk in Asians.     

DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk.

DNA repair efficiency varies among individuals, with reduced repair capacity as a risk factor for various cancers. This variability could be partly explained by allelic variants for different DNA repair genes. We examined the role of a common polymorphism in the XRCC3 gene (codon 241: threonine to methionine change) and bladder cancer risk. This gene plays a role in the homologous recombination pathway, which repairs double-strand breaks. The functional consequences of the XRCC3 codon 241 polymorphism are still unknown. We hypothesized that this polymorphism could affect repair of smoking-associated DNA damage and could thereby affect bladder cancer risk. We genotyped 233 bladder cancer cases and 209 controls who had been frequency matched to cases on age, sex, and ethnicity. We observed little evidence of a positive association between subjects who carried at least one copy of the codon 241 Met allele and bladder cancer (odds ratio: 1.3; 95% confidence interval: 0.9-1.9). Among heavy smokers, individuals with the Met allele had about twice the risk of those without it; however, a test of interaction was not statistically significant (P = 0.26). Previously, we observed in these subjects an association between bladder cancer risk and allelic variants of the XRCC1 gene, which is involved in the repair of base damage and single-strand breaks. In this study, we found some evidence for a gene-gene interaction between the XRCC1 codon 194 and XRCC3 codon 241 polymorphisms (P = 0.09) and some support for a possible gene-gene-smoking three-way interaction (P = 0.08).     

No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women's Health Study

BACKGROUND: Genetic variation in DNA repair may contribute to differences in the susceptibility of several cancers. We evaluated two polymorphisms in the base excision repair pathway (BER) (XRCC1; Arg194Trp and Arg399Gln) and one polymorphism in the double strand DNA repair pathway (XRCC3; Thr241Met) for their association with breast cancer risk. METHODS: The association was analyzed in a nested case control study of 460 breast cancer cases and 324 cancer-free controls within the Iowa Women's Health Cohort. DNA was obtained from blood samples or paraffin embedded tissues (PET) and all samples were genotyped by one of three genotyping platforms-PCR-RFLP, PCR-INVADER, or Sequenom. RESULTS: None of the three polymorphisms studied were significantly associated with breast cancer risk (XRCC1: Arg194Trp (OR=1.21, 95% CI: 0.78-1.88); Arg399Gln (OR=1.20, 95% CI: 0.80-1.79); XRCC3: Thr241Met (OR=1.04, 95% CI: 0.76-1.41). CONCLUSIONS: These results suggest that independently these polymorphisms of XRCC1 and XRCC3 genes do not contribute significantly to the genetic susceptibility of breast cancer.     

Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk

The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case–control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (OR_{Met allele vs. Thr allele}?=?1.17, 95 % CI 0.97–1.42, P _OR?=?0.102; OR_{MetMet vs. ThrThr}?=?1.32, 95 % CI 0.93–1.87, P _OR?=?0.121; OR_{ThrMet vs. ThrThr}?=?1.17, 95 % CI 0.94–1.45, P _OR?=?0.150; OR_{MetMet + ThrMet vs. ThrThr}?=?1.20, 95 % CI 0.96–1.51, P _OR?=?0.114; OR_{MetMet vs. ThrThr + ThrMet}?=?1.37, 95 % CI 0.98–1.93, P _OR?=?0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case–control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.     

XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis

Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of exogenous and endogenous substrates. The metabolism of polycyclic aromatic hydrocarbons and other procarcinogens through CYP1B1 may well lead to their activation. Apart from the extensively studied Val432Leu polymorphism, three single nucleotide polymorphisms in CYP1B1 have been studied concerning their potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and Asn453Ser. This meta-analysis aims to examine whether the three aforementioned polymorphisms are associated with breast cancer risk. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy–Weinberg equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were 0.933 (0.808–1.078) for heterozygous and 0.819 (0.610–1.100) for homozygous Gly subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896–1.097) for heterozygous and 0.935 (0.729–1.198) for homozygous Ser subjects. With respect to Asn453Ser, the pooled ORs were 0.961 (0.906–1.019) for heterozygous and 0.984 (0.846–1.144) for homozygous Ser subjects. In conclusion, this meta-analysis suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not associated with breast cancer risk. Studies on Chinese populations are needed, to elucidate race-specific effects on East Asian populations, if any.     

Association between the XRCC3 C241T polymorphism and lung cancer risk in the Asian population

X-ray repair cross-complementing group 3 (XRCC3) plays a vital role in maintaining the stability of genome by homologous recombination repair for DNA double-strand breaks. The genetic polymorphism of XRCC3 C241T has been implicated in lung cancer risk, but the findings across published studies in Asians are inconsistent and inconclusive. To estimate the precise association of XRCC3 C241T polymorphism with lung cancer risk, a meta-analysis of all currently available studies in Asians was performed. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases was conducted for eligible studies based on the inclusion criteria. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to assess the association. Besides, subgroup analysis and sensitivity analysis were also performed for further estimation. Seven available studies with a total of 7,398 subjects were finally included into this meta-analysis. The overall ORs indicated that the XRCC3 C241T polymorphism was not associated with a lung cancer risk among Asians in all genetic contrast modes (OR_{T allele vs. C allele}?=?1.08, 95 % CI 0.95–1.24, P _OR?=?0.252; OR_{TT vs. CC}?=?1.30, 95 % CI 0.69–2.45, P _OR?=?0.426; OR_{CT vs. CC}?=?1.07, 95 % CI 0.93–1.24, P _OR?=?0.363; OR_{TT + CT vs. CC}?=?1.08, 95 % CI 0.94–1.24, P _OR?=?0.300; OR_{TT vs. CC + CT}?=?1.29, 95 % CI 0.68–2.43, P _OR?=?0.439). We failed to identify significant association between the XRCC3 C241T polymorphism and risk of lung cancer in Chinese and population-based studies. Interestingly, the pooled ORs in hospital-based studies indicated that the XRCC3 C241T variant carriers were more susceptible to lung cancer (OR_{T allele vs. C allele}?=?1.27, 95 % CI 1.04–1.56, P _OR?=?0.019; OR_{CT vs. CC}?=?1.26, 95 % CI 1.01–1.57, P _OR?=?0.045; OR_{TT + CT vs. CC}?=?1.28, 95 % CI 1.03–1.59, P _OR?=?0.027). Sensitivity analysis confirmed the stability and liability of all results. This meta-analysis suggests that the XRCC3 C241T polymorphism may not exert a risk effect on the lung cancer risk in Asians, although a statistically significant association was observed among the hospital-based studies. Thus, the precise relationship between the XRCC3 C241T variant and lung cancer risk needs further confirmation in future studies with large available data.     

XRCC3 T241M polymorphism is associated risk of hepatocellular carcinoma in the Chinese

The X-ray repair cross-complementing group 3 (XRCC3) gene has been suggested to play an important role in the pathogenesis of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of XRCC3 Thr241Met variant with HCC. The published literature from PubMed, Chinese National Knowledge Infrastructure, and Wan Fang data was retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed or random effects model. A total of five studies (1,531 HCC cancer cases and 1,952 controls) for XRCC3 Thr241Met variant were included in the meta-analysis. The meta-analysis showed that XRCC3 Thr241Met variant was associated with HCC risk under homogeneous codominant model (OR?=?3.99, 95 % CI?=?1.74–9.13) and recessive model (OR?=?5.22, 95 % CI?=?3.65–7.48), but not under heterogeneous codominant model (OR?=?1.18, 95 % CI?=?0.68–2.05) and dominant model (OR?=?1.37, 95 % CI?=?0.73–2.57). Subgroup analysis by ethnicity suggested that XRCC3 Thr241Met variant was associated with HCC risk in Chinese population, but not in Pakistani population. The present meta-analysis supported the positive association of XRCC3 Thr241Met variant with HCC in the Chinese. Further large-scale studies with the consideration for gene–gene/gene–environment interactions should be conducted to investigate the association.     

Significant association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma: a meta-analysis

Many studies were published to examine the association between XRCC3 C241T polymorphism and hepatocellular carcinoma risk, but their results were inconsistent. To assess the association between XRCC3 C241T polymorphism and hepatocellular carcinoma risk more precisely, a meta-analysis was performed. PubMed, Embase and Wanfang databases were searched for relevant case–control studies. Data were extracted, and the pooled odds ratios (OR) with 95 % confidence intervals (95 % CI) were calculated. Finally, seven studies comprising 2,288 cases with hepatocellular carcinoma and 3,249 controls were included into the meta-analysis. Overall, there was an obvious association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma (TT versus CC: OR?=?3.31, 95 % CI 1.52–7.19, P?=?0.003; TT versus CC/CT: OR?=?3.31, 95 % CI 1.81–6.06, P?<?0.001). After adjusting for heterogeneity, there was still an obvious association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma (TT versus CC: OR?=?1.92, 95 % CI 1.13–3.26, P?=?0.016; TT versus CC/CT: OR?=?2.10, 95 % CI 1.25–3.55, P?=?0.005). Overall, there is a significant association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma. Further studies are needed to further assess the association in Caucasians.     

An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer

Variability in DNA repair genes may contribute to human cancer risk. We performed a case-control study (51 cases and 100 controls) to test the association between two polymorphisms: Arg399Gln in the XRCC1 gene and Thr241Met in the XRCC3 gene and colorectal cancer risk. Genotypes were determined in tumour tissue and distant mucosa samples by PCR RFLP with the NciI restriction enzyme for XRCC1 and NcoI for XRCC3. Cancer occurrence was strongly associated with the XRCC3 Met/Met polymorphic variant (OR = 9.45; (95% CI 8.77-11.65)), whereas Thr/Thr and Thr/Met variants were associated with significant reduction in colorectal cancer risk (OR = 0.16; 95% CI 0-0.26 and OR = 0.26; 95% CI 0.25-0.27, respectively). Weak association was found between the XRCC1 Arg/Arg and Gln/Gln variants and the risk of colorectal cancer (OR = 1.28; 95% CI 1.00-1.84 and OR = 1.13; 95% CI 0.85-2.34, respectively). Gene-gene interaction between the XRCC1 Arg/Arg and XRCC3 Met/Met homozygous variants slightly increased the risk (OR = 10.50; 95% CI 5.67-14.79). Both polymorphisms were not associated with colorectal cancer progression.     

Polymorphisms of DNA repair gene XRCC3 Thr241Met and risk of gastric cancer in a Chinese population

Mammalian cells are constantly exposed to a wide variety of genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair may contribute to human cancer risk. In this population-based case-control study in China, we tested the hypothesis that a C to T variant (Thr241Met) of DNA repair gene XRCC3 (X-ray repair cross-complementing group 3) is associated with risk of developing gastric cancer. We genotyped for this variant using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) in 188 histologically confirmed gastric cancer patients and 166 frequency-matched cancer-free controls. The XRCC3 genotype and allele frequencies were not significantly different between cases and controls (P = 0.99 for genotype; P = 0.76 for allele). The XRCC3 241Met allele frequency (4.8%) was significantly lower in healthy Chinese controls than previously reported healthy US Caucasian controls (38.9%). Compared with the XRCC3 241Thr/Thr genotype, the variant XRCC3241Thr/Met and Met/Met genotypes were not associated with an increased risk of gastric cancer (adjusted odds ratio (OR(a)), 1.06; 95% confidence interval (CI), 0.52-2.16). These findings suggest that polymorphisms of XRCC3 Thr241Met may not play a role in the etiology of gastric cancer. Further studies with a larger number of subjects and simultaneous measurement of different polymorphisms in DNA repair genes in the same pathway are needed to confirm these findings.     

Polymorphisms in the DNA repair gene XRCC1 and breast cancer.

X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in base excision repair. We examined the association of polymorphisms in XRCC1 (codon 194 Arg-->Trp and codon 399 Arg-->Gln) and breast cancer in the Carolina Breast Cancer Study, a population-based case-control study in North Carolina. No association was observed between XRCC1 codon 194 genotype and breast cancer, and odds ratios (ORs) were not modified by smoking or radiation exposure. A positive association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with Arg/Arg was found among African Americans (253 cases, 266 controls; OR = 1.7, 95% confidence interval, 1.1-2.4) but not whites (386 cases, 381 controls; OR =1.0, 95% confidence interval, 0.8-1.4). Among African-American women, ORs for the duration of smoking were elevated among women with XRCC1 codon 399 Arg/Arg genotype (trend test; P < 0.001) but not Arg/Gln or Gln/Gln (P = 0.23). There was no difference in OR for smoking according to XRCC1 codon 399 genotype in white women. ORs for occupational exposure to ionizing radiation were stronger for African-American and white women with codon 399 Arg/Arg genotype. High-dose radiation to the chest was more strongly associated with breast cancer among white women with XRCC1 codon 399 Arg/Arg genotype. Our results suggest that XRRC1 codon 399 genotype may influence breast cancer risk, perhaps by modifying the effects of environmental exposures. However, interpretation of our results is limited by incomplete knowledge regarding the biological function of XRCC1 alleles.     

No association between a polymorphism in the steroid metabolism gene CYP17 and risk of breast cancer.

A recent study showed an association between a single base substitution, T-->C, in the promotor region of the CYP17 gene, the risk of breast cancer and age at menarche in Asian, African-American and Latino women from California and Hawaii. The C allele was associated with increased risk of breast cancer, significantly so for patients presenting with advanced disease, whereas the TT genotype was associated with later age at menarche in control subjects. We attempted to confirm these findings in a large case-control study in East Anglia, England (835 cases and 591 control subjects). We found no evidence of an increased risk of breast cancer [odds ratio (OR) 1.10, confidence interval (CI) 0.89-1.37] or advanced breast cancer (OR 0.88, CI 0.38-2.01) in C allele carriers, nor any association between age at menarche and genotype. We conclude that these alleles do not significantly alter breast cancer risk in the English population.