Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans

Glutathione S:-transferase M1 (GSTM1) can detoxify many carcinogens, including polycyclic aromatic hydrocarbons such as those from cigarette smoke. Though a number of studies have been published about the association between GSTM1 polymorphism and lung cancer, this association has received limited attention in the African-American population. We conducted a case-control study to investigate the role of GSTM1 polymorphism in the development of lung cancer in African-Americans. Specimens of DNA from 117 lung cancer cases and 120 controls were assayed for detection of GSTM1 genotype by polymerase chain reaction (PCR). The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene and other risk factors were estimated by logistic regression. Thirty-seven of the 117 cases (31. 6%) and 24 of the 120 controls (20.0%) had the GSTM1 null genotype; the OR was 2.10 (95% CI 1.07-4.11) after adjustment for age, gender and smoking. The association was higher for squamous cell carcinoma (OR 2.98, 95% CI 1.09-8.19) than for adenocarcinoma (OR 1.95, 95% CI 0.81-4.66). We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with > or =30 pack-years (OR 4.35, 95% CI 1.16-16.23). This association was also found in squamous cell carcinoma (OR 6.26, 95% CI 1.31-29.91). In the analysis combining GSTM1 polymorphism and smoking, smokers with the null genotype had high risk (OR 8.19, 95% CI 2.35-28.62) compared with non-smokers with the wild-type genotype, and the risk increased with smoking cigarette pack-years (P: = 0.0001 for trend). Our results suggest that GSTM1 polymorphism plays a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in African-Americans.     

Food groups and colon cancer risk in African-Americans and Caucasians

The disparities in colon cancer incidence between African-Americans and other U.S. ethnic groups are largely unexplained. This report examines associations of various food groups with colon cancer in African-Americans and Caucasians from a case-control study. Incident cases of histologically confirmed colon cancer, age 40-80 years, (n = 613) and matched controls (n = 996) were interviewed in-person to ascertain potential colon cancer risk factors. Diet over the year before diagnosis or interview date was assessed using a validated food frequency questionnaire adapted to include regional foods. Multivariate logistic regression models estimated energy-adjusted and non-energy adjusted odds ratios (OR). Controls generally reported higher consumption (daily amount and weekly frequency) of fruits, vegetables and dark green, deep yellow fruits/vegetables, whereas cases consumed more refined carbohydrates and fats, oils and snacks. Regardless of ethnic group or energy adjustment, high and frequent vegetable consumption (particularly dark green vegetables) was protective, consistent with 20-50% reductions in risk. In Caucasians, high refined carbohydrate and red meat consumption (amount and frequency) was associated with a statistically significant 2-fold increased risk in non-energy adjusted models. In African-Americans, frequent intake of dairy foods was associated with a doubling in risk (OR = 1.9, 95% CI = 1.1-3.4) in non-energy-adjusted models, whereas frequent fruit consumption correlated with a non-significant 30% lower risk. These findings add to growing evidence that plant foods may protect against colon cancer; however, the effects of the other food groups varied by ethnic group and energy adjustment. These results may also explain some of the ethnic differences in colon cancer incidence.     

Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.

Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.     

Genetic polymorphisms of XRCC1 and risk of gastric cancer

Coding polymorphisms of the DNA repair gene XRCC1 have been shown to affect the DNA repair capacity and to be associated with genetic susceptibility to carcinogenesis. In our association study between three amino acid substitution polymorphisms of XRCC1 (Arg194Trp, Arg280His, and Arg399Gln) and the risk of gastric cancer in the Korean population, none of the polymorphisms were associated with increased risk of gastric cancer. We then extended our study by building haplotypes of the entire XRCC1 gene with six single neuclotide polymorphisms (SNPs), including two novel polymorphisms at the 5'-flanking sequence. When haplotype frequencies in cases and controls and haplotype-specific odds ratios (ORs) were estimated, haplotype A (194Trp, 280Arg, and 399Arg) was associated with significant reduction in gastric cancer risk (adjusted OR=0.65, 95% CI=0.43-0.99) whereas haplotype D (194Arg, 280Arg, and 399Arg alleles) was a risk type for gastric cancer (adjusted OR=1.57, 95% CI=0.93-2.65). The association with the haplotype D was more pronounced in the cancers of antrum (adjusted OR=2.06, 95% CI=1.03-2.00). Our results suggest that the haplotype estimation is advantageous for association studies of such a complex disease as gastric cancer.     

CYP1B1 Leu432Val polymorphism and colorectal cancer risk among Caucasians: a meta-analysis

Studies investigating the association between cytochrome P450 1B1 (CYP1B1) Leu432Val (432 C/G, rs1056836) polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP1B1 polymorphism and CRC were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed for co-dominant model (GG vs. CC, GC vs. CC), dominant model (GG + GC vs. CC), and recessive model (GG vs. GC + CC). This meta-analysis included ten case–control studies, which included 8,466 CRC cases and 9,301 controls. Overall, the variant genotypes (GG and GC) of the 432 C/G were not associated with CRC risk when compared with the wild-type CC homozygote (GG vs. CC, OR = 1.01, 95% CI = 0.93–1.10; GC vs. CC, OR = 0.97, 95% CI = 0.90–1.04), without any between-study heterogeneity. Similarly, no associations were found in the dominant and recessive models (dominant model, OR = 0.98, 95% CI = 0.92–1.05; recessive model, OR = 1.03, 95% CI = 0.96–1.11). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. When stratifying for country, matched control and source of controls, no evidence of significant association was observed in any subgroup. No publication bias was found in the present study. No association is found between the CYP1B1 Leu432Val polymorphism and risk of CRC among Caucasians.     

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk

Objectives: The human GSTTP1 gene is polymorphic with an A G transition in exon 5 causing a replacement 105 IleVal in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.     

XRCC1 Arg194Trp多态性与亚洲人群肺癌易感性的Meta分析

目的:应用Meta分析方法评价XRCC1 Arg194Trp基因多态性与亚洲人群肺癌易感性的关系。方法:计算机检索Pubmed、Embase、Cochrane图书馆、万方、CNKI、维普和CBM数据库,全面收集有关XRCC1Arg194Trp基因多态性与亚洲人群肺癌易感性的相关研究。结果:根据入组标准,共13个病例对照研究纳入本系统评价,共计5585例研究对象,其中包括2629例肺癌患者和2956例健康正常人。Meta分析结果表明:XRCC1 194Arg等位基因(ORArg=1.01,95%CI=0.90-1.14,P=0.84)、194Trp携带者(ORArg/Trp+Trp/Trp=1.04,95%CI=0.93-1.15,P=0.50)及194Arg携带者(ORArg/Arg+Arg/Trp=1.14,95%CI=0.94-1.37,P=0.18)均与亚洲人群肺癌易感性无明显统计学关联。结论:虽然194Trp等位基因及其携带者可能导致XRCC1修复DNA损伤能力的降低,但XRCC1 Arg194Trp多态性与亚洲人群肺癌易感性并无明确统计学关联。     

Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk.

We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. 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. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.     

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical-associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (+/-3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15-6.67) as compared with the XRCC1(399) Arg/Gln and XRCC1(399) Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol-associated esophageal cancers.     

ERCC2 Lys751Gln polymorphism is associated with lung cancer among Caucasians

To derive a more precise estimation of the relationship between the excision repair cross-complementing rodent repair deficiency, group 2 (ERCC2) Lys751Gln polymorphism and lung cancer risk, a meta-analysis was performed. A total of 23 studies including 8137 cases and 9824 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with ERCC2 Gln allele when all studies were pooled into the meta-analysis (Lys/Gln versus Lys/Lys: odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.03–1.19; Gln/Gln versus Lys/Lys: OR = 1.20, 95% CI = 1.06–1.35; dominant model: OR = 1.13, 95% CI = 1.05–1.20; and recessive model: OR = 1.15, 95% CI = 1.03–1.29). In the subgroup analysis by ethnicity, significantly increased risk was only found for Caucasians (Gln/Gln versus Lys/Lys: OR = 1.25, 95% CI = 1.08–1.45; dominant model: OR = 1.10, 95% CI = 1.00–1.22; and recessive model: OR = 1.22, 95% CI = 1.06–1.40). When stratified by study design, statistically significantly elevated risks were found in hospital-based studies (Lys/Gln versus Lys/Lys: OR = 1.12, 95% CI = 1.03–1.22; Gln/Gln versus Lys/Lys: OR = 1.24, 95% CI = 1.06–1.44; dominant model: OR = 1.15, 95% CI = 1.06–1.24; and recessive model: OR = 1.19, 95% CI = 1.03–1.37) and population-based studies (Gln/Gln versus Lys/Lys: OR = 1.57, 95% CI = 1.12–2.20 and recessive model: OR = 1.50, 95% CI = 1.08–2.07). In the subgroup analysis whether or not the studies were matched on smoking, significantly increased risk was found not in those matched studies but in the unmatched studies (Lys/Gln versus Lys/Lys: OR = 1.11, 95% CI = 1.03–1.19; Gln/Gln versus Lys/Lys: OR = 1.22, 95% CI = 1.07–1.40; dominant model: OR = 1.13, 95% CI = 1.05–1.22; and recessive model: OR = 1.18, 95% CI = 1.04–1.33). In conclusion, this meta-analysis suggests that the ERCC2 Lys751Gln polymorphism may contribute to lung cancer susceptibility among Caucasians.     

XRCC3 polymorphisms and risk of lung cancer

In a nested case-cohort study, we have investigated the occurrence of lung cancer in relation to polymorphisms in the double strand DNA repair gene XRCC3. Among 54,220 members of a Danish prospective cohort study aged 50-65 at entry, 265 lung cancer cases were identified and a sub-cohort, matched by age, sex and duration of smoking, comprising of 272 individuals was used for comparison. Ninety percent of both cases and comparison group were ever-smokers. Three previously studied polymorphisms; XRCC3 A4541G (5'UTR), A17893G (IVS5-14) and C18067T (T241M) were combined into haplotypes. The four most frequent haplotypes accounted for 98% of the genotypes. Homozygosity for the haplotype AAC was associated with a 4.91 times higher risk of lung cancer (confidence interval, 95% CI = 1.06-22.81) compared with the GAC haplotype. The polymorphism XRCC3 IVS6 C1571T was found to co-segregate with the AAC haplotype, and homozygous carriers of the variant T-allele had a 4.47 (CI = 1.34-14.96) times higher risk of lung cancer compared with homozygous carriers of the wild type allele. Our results indicate that XRCC3 IVS6 C1571T and the associated haplotype AAC are associated with relatively high risk of lung cancer.     

Glutathione S-transferase P1 gene polymorphism associated with gastric cancer among Caucasians

Studies investigating the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 10 case-control studies, which included 1161 gastric cancer cases and 2847 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR) = 1.14, 95% confidence interval (CI) = 0.91, 1.44; AG (OR=0.82, 95% CI = 0.66, 1.03); GG (OR = 1.11, 95% CI = 0.55, 2.24)] between gastric cancer and non-cancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly higher frequency of AA (OR = 1.53, 95% CI = 1.14, 2.06) and lower frequency of AG (OR = 0.70, 95% CI = 0.55, 0.89) than non-cancer patients among Caucasians. When stratifying by the location and Lauren’s classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the GSTP1 codon 105 polymorphism may be associated with gastric cancer among Caucasians.     

Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer.

DNA repair plays a critical role in protecting the genome of the cell from insults of cancer-causing agents, such as those found in tobacco smoke. Reduced DNA repair capacity, therefore, can increase the susceptibility to smoking-related cancers. Recently, three coding polymorphisms in X-ray cross-complementing group 1 (XRCC1) DNA repair gene have been identified, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility. We investigated the relationship between the codon 399 polymorphism in XRCC1 gene and lung cancer risk in male smokers. The study population consisted of 192 lung cancer patients and 135 healthy controls. The distribution of XRCC1 genotypes was not significantly different between cases and controls. When the cases were categorized by histological type, however, the presence of at least one Gln allele was associated with a significant increased risk for squamous cell carcinoma [crude odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.06-2.93 and adjusted OR = 1.66, 95% CI = 0.99-2.79]. The risk for the disease increased as the number of Gln alleles increased (Arg/Gln genotype: adjusted OR = 1.45, 95% CI = 0.84-2.5; Gln/Gln genotype: adjusted OR = 3.26, 95% CI = 1.17-9.15). When the subjects dichotomized by cigarette consumption into two pack-year groups (< or =40 pack-years, >40 pack-years), the Gln allele was associated with an increased risk for squamous cell carcinoma only in the group of individuals having < or =40 pack-years of smoking (Arg/Gln genotype: adjusted OR = 1.48, 95% CI = 0.78-2.8; Gln/Gln genotype: adjusted OR = 5.75, 95% CI = 1.46-22.69). These results suggest that XRCC1 codon 399 polymorphism may be an important genetic determinant of squamous cell carcinoma of the lung in persons with lower degrees of cigarette use.     

Genetic polymorphism and cancer risk

Inter-individual variability in carcinogen metabolism has been attributed in part to the polymorphic expression of several phase I and II detoxification enzymes. The role of these genetic polymorphisms in cancer susceptibility has been most extensively evaluated for isozymes of cytochrome P450 (CYP1A1, CYP2D6, and CYP2E1), N-acetyltransferase (NAT1 and NAT2), glutathione S-transferase (GSTM1, GSTT1, and GSTP1), microsomal epoxide hydrolase, and NAD(P)H:quinone oxidoreductase. Our understanding of the genetic basis of cancer risk has been enhanced most recently by establishment of genotype-phenotype correlations in humans and identification of numerous diverse factors, both genetic and environmental, that can modify risk.     

Lung cancer risk in relation to genetic polymorphisms of microsomal epoxide hydrolase among African-Americans and Caucasians in Los Angeles County

Microsomal epoxide hydrolase participates in the metabolism of benzo[a]pyrene, an important carcinogen in tobacco smoke. Two relatively common polymorphisms of the microsomal epoxide hydrolase gene that influence enzyme activity have been described. An association between genetic variation in microsomal epoxide hydrolase and lung cancer risk has been reported in one of two studies of Caucasians. We examined the relation between these two polymorphisms and lung cancer risk among 337 incident cases and 700 population controls of African-American and Caucasian ethnicity enrolled in a case-control study in Los Angeles County. African-Americans, homozygous for the exon 3 variant allele conferring reduced activity, were at decreased risk of lung cancer (odds ratio (OR)=0.08, 95% CI 0.01-0.62). When data from both the exon 3 and exon 4 polymorphisms were combined into indices of predicted microsomal epoxide hydrolase activity, a decreased risk was seen among African-American subjects with very low predicted activity OR=0.10 (95% CI 0.01-0.83). No comparable association was seen among Caucasians. Although the three published results for Caucasians are somewhat variable, the association among African-Americans in these data provides some support for the hypothesis that genetically reduced microsomal epoxide hydrolase activity may be protective against lung cancer.     

GSTM1 polymorphism and lung cancer risk among East Asian populations: a meta-analysis

GSTM1 gene encodes a key enzyme involved in the metabolism of xenobiotics, and its polymorphisms have been related to individual susceptibility to several malignancies. Many molecular epidemiological studies were performed to investigate the association between the GSTM1 null polymorphism and lung cancer susceptibility in East Asia. However, the results were inconsistent. In order to derive a more precise estimation, we conducted this meta-analysis involving 5,909 lung cancer cases and 7,067 controls from 35 studies. We used crude odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the association between GSTM1 null genotype and the risk of lung cancer. Our study found that the GSTM1 null genotype appeared to be a significant risk factor for lung cancer in East Asia population (OR?=?1.30, 95 % CI?=?1.17–1.45, P _{heterogeneity}?<?0.0001, and I ²?=?54.0 %).     

The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy

PURPOSE: The X-ray repair cross-complementing Group 1 (XRCC1) protein is involved mainly in the base excision repair of the DNA repair process. This study examined the association of 3 polymorphisms (codon 194, 280, and 399) of XRCC1 and lung cancer in terms of whether or not these polymorphisms have an effect on the survival of lung cancer patients who have received radiotherapy. METHODS AND MATERIALS: Between January 2000 and April 2004, 229 lung cancer patients with non-small-cell lung cancer in Stages I-III were enrolled. Genotyping was performed by single base primer extension assay using the SNP-IT Kit with genomic DNA samples from all patients. The haplotype of the XRCC1 polymorphisms was estimated by PHASE version 2.1. RESULTS: The patients consisted of 191 (83.4%) males and 38 (16.6%) females with a median age of 62 (range, 26-88 years). Sixty percent of the patients were included in Stage I-IIIa. The median progression-free and overall survival was 13 months and 16 months, respectively. The XRCC1 codon 194, histology, and stage were shown to be significant predictors of the progression-free survival. The 6 haplotypes among the XRCC1 polymorphisms (194, 280, and 399) were estimated by PHASE v.2.1. The patients with haplotype pairs other than the homozygous TGG haplotype pairs survived significantly longer (p = 0.04). CONCLUSIONS: Polymorphisms of XRCC1 have an effect on the survival of lung cancer patients treated with radiotherapy, and this effect seems to be more significant after the haplotype pairs are considered.     

Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus

Population-based studies have reported significant associations between specific genetic polymorphisms and breast cancer susceptibility. A number of studies have demonstrated that common variants of genes involved in the DNA repair pathway act as low penetrance breast cancer susceptibility alleles. We aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the DNA repair genes XRCC1, XRCC2 and XRCC3 and breast cancer in MASTOS, a population-based case–control study of 1,109 Cypriot women with breast cancer diagnosed between 40 and 70 years and 1,177 age-matched healthy controls. Five coding SNPs were genotyped including rs1799782, rs25489 and rs25487 in XRCC1, rs3218536 in XRCC2 and rs861539 in XRCC3. Homozygous XRCC1 280His carriers had an increased risk of breast cancer (odds ratio 4.68; 95% CI 1.01–21.7; P = 0.03). The XRCC2 188His allele was associated with a marginal protective effect for breast cancer (odds ratio 0.79; 95% CI 0.62–1.00; P = 0.05). No significant associations were observed between the other three SNPs and breast cancer. This study suggests that genetic variation in SNPs in XRCC1 and XRCC2 genes may influence breast cancer susceptibility.