Single-nucleotide polymorphisms in one-carbon metabolism genes,Mediterranean diet and breast cancer risk: a case–control study in the Greek-Cypriot female population

Single-nucleotide polymorphisms (SNPs) within genes of the one-carbon metabolism pathway have been shown to interact with dietary folate intake to modify breast cancer (BC) risk. Our group has previously demonstrated that the Mediterranean dietary pattern, rich in beneficial one-carbon metabolism micronutrients, protects against BC in Greek-Cypriot women. We aimed to investigate whether SNPs in the MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) genes modify the effect of the Mediterranean dietary pattern on BC risk. Dietary intake data were obtained using a 32-item food-frequency questionnaire. A dietary pattern specific to the Greek-Cypriot population, which closely resembles the Mediterranean diet, was derived using principal component analysis (PCA) and used as our dietary variable. Genotyping was performed on subjects from the MASTOS study, a case–control study of BC in Cyprus, using TaqMan assays. Adjusted odds ratios (ORs) were estimated using logistic regression analyses. High adherence to the PCA-derived Mediterranean dietary pattern further reduced BC risk with increasing number of variant MTHFR 677T alleles (OR_Q4vs.Q1 for 677TT = 0.37, 95 % CI 0.20–0.69, for 677 CT = 0.60, 95 % CI 0.42–0.86). Additionally, high adherence to the Mediterranean dietary pattern decreased BC risk in subjects with at least one MTR 2756A allele (OR_Q4vs.Q1 for 2756AA = 0.59, 95 % CI 0.43–0.81, for 2756AG = 0.59, 95 % CI 0.39–0.91) and in subjects with the MTHFR 1298CC genotype (OR_Q4vs.Q1 0.44, 95 % CI 0.30–0.65). Overall P-interaction values, however, were not statistically significant. Our study suggests that these MTHFR and MTR SNPs may act as effect modifiers, highlighting their biological significance in the association between Mediterranean diet, the one-carbon metabolism pathway and BC.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0453-7) contains supplementary material, which is available to authorized users.     

HTERT MNS16A polymorphism in breast cancer: a case–control study

This case–control study aims to investigate the role of HTERT MNS16A polymorphism as a potential risk factors and/or a prognostic marker for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. HTERT MNS16A polymorphism was genotyped (L: long allele, S: short allele); multivariate logistic regression was performed. No significant association was noted either at the overall analysis (OR?=?1.57, 95?% CI 0.84–2.93 for heterozygous LS carriers; OR?=?1.02, 95?% CI 0.54–1.95 for homozygous SS carriers) or at the subanalyses in premenopausal and postmenopausal women. With respect to survival analysis, HTERT MNS16A polymorphism was not associated with either disease-free survival or overall survival. HTERT MNS16A polymorphism does not seem to be a risk factor for breast cancer in the Caucasian Greek population. Further, larger studies from other countries and subjects seem to be needed as this novel polymorphism is being examined in depth.     

2q35-rs13387042 variant and the risk of breast cancer: a case–control study

Molecular Biology Reports - Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease...     

Mitochondrial genome variations in advanced stage breast cancer: A case–control study

Entire mitochondrial DNA (mtDNA) sequencing was carried out in 101 primary breast cancer patients and 90 controls of south Indian origin. We identified 69 novel mutations in breast cancer patients and 637 reported polymorphisms in patients and/or controls. PolyPhen-2 analysis predicted 5 out of 14 novel missense mutations as ‘probably damaging variants’. Haplogrouping analysis identified a significant association between haplogroup M5 and breast cancer risk. Microsatellite instability and tumor specific large scale mtDNA deletions were not observed in tumor tissues from the patients. In conclusion, mtDNA mutations and haplogroups may constitute an inheritable risk factor for pathogenesis of breast cancer.     

The XRCC3 Thr241Met polymorphism and breast cancer risk: a case–control study in a Thai population

The X-ray repair cross-complementing group 3 gene (XRCC3) belongs to a family of genes responsible for repairing DNA double-strand breaks caused by normal metabolic processes and exposure to ionizing radiation. Polymorphisms in DNA repair genes may alter an individual's capacity to repair damaged DNA and may lead to genetic instability and contribute to malignant transformation. We examined the role of a polymorphism in the XRCC3 gene (rs861529; codon 241: threonine to methionine change) in determining breast cancer risk in Thai women. The study population consisted of 507 breast cancer cases and 425 healthy women. The polymorphism was analysed by fluorescence-based melting curve analysis. The XRCC3 241Met allele was found to be uncommon in the Thai population (frequency 0.07 among cases and 0.05 among controls). Odds ratios (OR) adjusted for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education were calculated for the entire population as well as for pre- and postmenopausal women. There was a significant association between 241Met carrier status and breast cancer risk (OR 1.58, 95% confidence interval (CI) 1.02–2.44). Among postmenopausal women, a slightly higher OR (1.82, 95% CI 0.95–3.51) was found than among premenopausal women (OR 1.48, 95% CI 0.82–2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry.     

XRCC1 gene polymorphisms and lung cancer susceptibility: a meta-analysis of 44 case–control studies

X-ray repair cross-complementing group 1 gene (XRCC1) has been implicated in risk for lung cancer. However, the results from different studies remain controversial. In this meta-analysis, we have assessed 44 published case-control studies regarding associations of lung cancer risk with three common polymorphisms, codon 194, codon 280 and codon 399, and -77 T?>?C in the promoter region of XRCC1. The results in total population showed that the risk for lung cancer was increased among the variant homozygote Trp/Trp of codon 194 polymorphism, compared with the wild type Arg/Arg (OR: 1.19; 95?% CI 1.01-1.39), and the variant genotype CC of -77 T?>?C polymorphism showed a significantly increased risk of developing lung cancer, compared to wild-type genotype TT (OR: 1.91; 95?% CI 1.24-2.94). However, no associations were found between lung cancer risk and codon 280, codon 399. In the subgroup analyses by ethnicity, the OR for the variant homozygote Trp/Trp of codon 194 was 1.21(95?% CI 1.02-1.43) for Asian. 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. Subgroup analyses by histological types of lung cancer indicated that the heterozygote Arg/Trp in codon 194 could decrease and the combined variant genotype Arg/Gln?+?Gln/Gln in codon 399 could increase the risk of non-small cell lung cancer (OR: 0.69; 95?% CI 0.57-0.85 and OR: 1.14; 95?% CI 1.04-1.24). In conclusion, this meta-analysis has demonstrated that codon 194, codon 399 and -77 T?>?C polymorphisms of XRCC1 gene might have contributed to individual susceptibility to lung cancer. To further evaluate effect of XRCC1 polymorphisms, gene-gene interaction and gene-environment interaction on lung cancer risk, a single large sample size study with thousands of subjects is required to get conclusive results.     

History of gonorrhea and prostate cancer in a population-based case–control study in Mexico

We evaluated the association between a history of sexually transmitted diseases (STDs) and the risk for prostate cancer (PC) among Mexican males.MethodsPC incident cases (n = 402) that were identified at six public hospitals in Mexico City were matched by age (±5 years) with 805 population controls with no history of PC. By face-to-face interview, we obtained information about sexual history, previous STDs, sociodemographic characteristics, and familial history of PC. An unconditional logistic regression model was used to estimate the risk for PC.ResultsA total of 16.6% of men reported having had at least one previous STD, and the most frequently reported STD was gonorrhea (10.5%). After adjusting by PC familial history, the history of STD was associated with a two-fold greater risk of PC: odds ratio (OR) = 2.67; 95% confidence interval (95% CI = 1.91–3.73). When each STD was evaluated separately, only gonorrhea was associated with a significant increase in PC risk (OR = 3.04; 95% CI = 1.99–4.64). These associations were similar when we stratified by low-risk PC (Gleason <7) and high-risk PC (Gleason ≥7).ConclusionThese results confirm that STDs, and particularly gonorrhea, may play an etiological role in PC among Mexican males, which is consistent with a previous report from a multiethnic cohort.     

Male pattern baldness and prostate cancer risk in a population-based case–control study

Purpose: Male pattern baldness (MPB) and prostate cancer (PCa) share commonality as prevalent, heritable and androgen-related conditions. Studies exploring the relationship between the two conditions have been inconclusive. Using a population-based, case–control study of PCa, we explore the relationship between early-onset MPB and PCa risk. Methods: Cases were men aged 35–74 diagnosed with PCa between 2002 and 2005 in King County, Washington. Controls were frequency matched by age and identified by random digit dialing. Hair pattern at age 30 and at 1 year prior to diagnosis (cases) or reference date (controls) was determined using showcards. PCa risk associated with balding was assessed with logistic regression. Results: Data from 999 cases of PCa and 942 controls were analyzed. Hair loss at age 30 was more common in controls (25.2%) than cases (19.8%, p = 0.005), and those with hair loss at age 30 had a 29% relative risk reduction for PCa (OR 0.71, 95% CI 0.56–0.91). No risk reduction was seen for men only reporting hair loss at referent age (OR 0.90, 95% CI 0.73–1.12). In men aged >60 at referent date, the risk reduction was greater for men with hair loss at age 30 from both the top of head and forehead (OR 0.55, 95% CI 0.33–0.93). Conclusion: Early-onset MPB was associated with a reduced relative risk of PCa in this population-based study. Further research into a possible mechanistic link between these prevalent and androgen-related conditions is warranted.     

Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case–control studies

The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04–1.16) and in additive model (OR = 1.10, 95% CI = 1.03–1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82–0.99) and dominant model (OR = 0.94, 95% CI = 0.89–0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.     

DNA methylation in pre-diagnostic serum samples of breast cancer cases: Results of a nested case–control study

Background: Promoter methylation of tumor suppressor genes is a frequent and early event in breast carcinogenesis. Paired tumor tissue and serum samples from women with breast cancer show that promoter methylation is detectable in both sample types, with good concordance. This suggests the potential for these serum markers to be used for breast cancer detection. Methods: The current study was a case–control study nested within the prospective New York University Women's Health Study cohort aimed to assess the ability of promoter methylation in serum to detect pre-clinical disease. Cases were women with blood samples collected within the 6 months preceding breast cancer diagnosis (n = 50). Each case was matched to 2 healthy cancer-free controls and 1 cancer-free control with a history of benign breast disease (BBD). Results: Promoter methylation analysis of four cancer-related genes: — RASSF1A, GSTP1, APC and RARβ2, — was conducted using quantitative methylation-specific PCR. Results showed that the frequency of methylation was lower than expected among cases and higher than expected among controls. Methylation was detected in the promoter region of: RASSF1A in 22.0%, 22.9% and 17.2% of cases, BBD controls and healthy controls respectively; GSTP1 in 4%, 10.4% and 7.1% respectively; APC in 2.0%, 4.4% and 4.2% respectively and RARβ2 in 6.7%, 2.3% and 1.1% respectively. Conclusion: Methylation status of the four genes included in this study was unable to distinguish between cases and either control group. This study highlights some methodological issues to be addressed in planning prospective studies to evaluate methylation markers as diagnostic biomarkers.     

MMP-2 −1306C > T polymorphism in breast cancer: a case–control study in a South European population

This case control study aims to investigate the role of MMP-2 ?1306C > T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 ?1306C > T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 ?1306C > T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 ?1306C > T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 ?1306C > T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 ?1306C > T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed.     

Lysyl oxidase polymorphisms and ischemic stroke—a case control study

Ischemic stroke is a common neurological disease and causes severe disability and death worldwide. Lysyl oxidase (LOX) plays a crucial role in the maintenance of extracellular matrix stability and may participate in vascular remodeling in the development of ischemic stroke. The objective of this study is to identify polymorphisms in LOX genes and investigate the association between LOX polymorphisms and the susceptibility to ischemic stroke in the Chinese population. Genomic DNA sequencing analysis was performed on all 7 exons and all exon/intron splice sites of lysyl oxidase and 850?bp upstream, including the predicted promoter region in 25 control subjects. The identified polymorphisms were then detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 702 ischemic stroke cases and 733 age-matched controls. Data were analyzed using the Chi-square test. Two polymorphisms in the LOX gene, 473G/A (rs1800449) and rs2278226, were observed in the Chinese population. Frequencies of LOX 473AA genotype and A allele were significantly higher in ischemic stroke patients than in controls (odds ration (OR)?=?1.76, 95?% confidence interval (CI) 1.16-2.67, P?=?0.007; and OR?=?1.33, 95?% CI 1.10-1.60, P?=?0.003). Also, the prevalence of AC haplotype was significantly increased in ischemic stroke cases (OR?=?1.32, 95?% CI 1.10-1.60, P?=?0.004). Our data suggest that the G473A polymorphism of LOX gene could be a new risk factor for ischemic stroke.     

DNMT3B polymorphisms and cancer risk: a meta analysis of 24 case–control studies

The association between polymorphism of DNA methyltransferases 3B and cancer risk has been widely studied recently, and no consensus conclusion is available up to now. We perform a comprehensive search using the databases of Medline, ISI Web of Knowledge and Embase. The odds ratio (OR) and its 95% confidence interval (95% CI) are used to investigate the strength of the association. A total of 24 case–control studies with 15,647 individuals are included in this meta-analysis. For −149C > T (17 studies, 5229 cases and 6910 controls), no evidence indicate that individuals carrying the variant genotypes (CC + CT), relative to those carrying the wild homozygote TT genotype, have an increased risk of cancer (OR = 1.03; 95% CI = 0.84–1.26; P = 0.76). Similarly, no cancer risk is found in the subgroup analyses. For −579G > T (11 studies, 3513 cases and 3714 controls), significantly decreased risks of cancer are observed, and the ORs (95% CI) are 0.70 (0.56–0.87) for GT versus TT, 0.70 (0.57–0.85) for GG + GT versus TT and 0.76 (0.63–0.93) for G-allele versus T-allele, respectively. Subgroup analyses stratified by ethnicity and types of cancer are also performed, and results indicated that −579G > C polymorphism is associated with risk of cancer in Asians [0.68 (0.53–0.87) for GT vs. TT] but not in Europeans [0.82 (0.63–1.07) for GT vs. TT]. We also observe that the −579G is associated with decreased risk of colorectal cancer [0.49(0.38–0.62) for GT vs. TT]. More studies with larger sample size were needed to provide more precise evidence.     

Prolonged breastfeeding reduces risk of breast cancer in Sri Lankan women: A case–control study

Goal: To assess the association between duration of breastfeeding and the risk of breast cancer in Sri Lankan women. Methods: We conducted a case–control study in women aged 30–64 years in selected health care facilities in the Western province. A total of 100 recent cases of breast cancer (histologically confirmed) and 203 controls (age and parity matched) were included. Detailed information regarding breastfeeding, menstruation, reproductive factors, passive smoking and other confounders was collected using a structured questionnaire. Adjusted odds ratios and 95% confidence intervals were calculated using multiple logistic regressions. Principle results: Multivariate analysis found that those women who breastfed for ≥24 months during lifetime had significantly lower risk of breast cancer than those who breastfed for less than 24 months (OR = 0.40; 95%CI = 0.22, 0.73). Compared to 0–11 months of lifetime breastfeeding, there was a 66.3% reduction in breast cancer risk in women who breastfed for 12–23 months, 87.4% reduction in 24–35 months and 94% reduction in 36–47 months categories. The mean duration of breastfeeding per child for ≥12 months was also associated with reduced risk of breast cancer (OR = 0.52; 95%CI = 0.28, 0.94). The significant factors associated with increased risk of breast cancer were: post-menopausal women (OR = 1.74; 95%CI = 1.01, 3.01); having an abortion in the past (OR = 3.42; 95%CI = 1.75, 6.66) and exposure to passive smoking (OR = 2.96, 95%CI = 1.53, 5.75). Major conclusions: Prolonged breastfeeding significantly reduces the risk of breast cancer and this protective effect was supported by a dose–response relationship. Risk due to passive smoking should be emphasized in anti-smoking programmes.     

PCMT1 gene polymorphisms, maternal folate metabolism, and neural tube defects: a case–control study in a population with relatively low folate intake

The PCMT1 gene encodes the protein repair enzyme protein-l-isoaspartate (d-aspartate) O-methyltransferase, which is known to protect certain neural cells against Bax-induced apoptosis. Previous studies have produced inconsistent results regarding the effects of PCMT1 (rs4816 and rs4552) polymorphisms on neural tube defects (NTDs). Reduced maternal plasma folate levels and/or elevated homocysteine (Hcy) levels are considered to be risk factors for NTDs. In order to clarify the key factors contributing to the apparent discrepancy and investigate gene–environment interaction, we conducted a case–control study including 121 cases and 146 matched controls to investigate the association between the two PCMT1 polymorphisms in fetuses and the risk of NTDs in the Chinese population of Lvliang, which has low folate intake. Maternal plasma folate and Hcy levels were also measured, and the interaction between fetal PCMT1 gene status and maternal folate metabolites was assessed. Maternal plasma folate concentrations in the NTD group were lower than in controls (10.23 vs. 13.08 nmol/L, adjusted P = 0.059), and Hcy concentrations were significantly higher (14.46 vs. 11.65 μmol/L, adjusted P = 0.026). Fetuses carrying the rs4816 AG + GG genotype, combined with higher maternal plasma Hcy, had a 6.46-fold (95 % CI 1.15–36.46) increased risk of anencephaly. The results of this study imply that the fetal PCMT1 rs4816 polymorphism may play only a weak role in NTD formation and that gene–environment interactions might be more significant.     

Association between XRCC1 and XRCC3 polymorphisms and colorectal cancer risk: a meta-analysis of 23 case–control studies

Several potential functional polymorphisms in the DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln (rs25487), Arg194Trp (rs1799782), Arg280His (rs25489) and X-ray repair cross-complementing group 3 (XRCC3) T241M (rs861539) have been implicated in colorectal cancer (CRC) risk, but the results are conflicting. Here, we performed a meta-analysis of 23 published case control datasets and assessed genetic heterogeneity between those datasets. All the case–control studies published from January 2000 to June 2012 on the association between those polymorphisms and CRC risk were identified by searching the electronic literature Medline. Statistical analysis was performed with the software programs Review Manager (version 4.2). For overall CRC, no significant association was observed, the pooled odds ratios for XRCC1 Arg399Gln, Arg194Trp, Arg280His, and XRCC3 T241M were 1.02 (95 % CI: 0.93, 1.12), 1.03 (95 % CI: 0.94, 1.14), 0.98 (95 % CI: 0.85, 1.13) and 1.03 (95 % CI: 0.85, 1.26), respectively. Furthermore, no significant association was observed in subgroup analyses based on ethnicity. The results suggested that these four SNPs evaluated are not associated with risk of CRC.     

Polymorphisms in TP53 and MDM2 contribute to higher risk of colorectal cancer in Chinese population: a hospital-based, case–control study

The murine double minute 2 protein (MDM2) and TP53 interact in regulating cell cycle, DNA repair and apoptosis process, which is crucial in carcinogenesis. Since functional variations in these two genes were shown to change gene expression and function, we hypothesized that potentially functional polymorphisms in these genes may contribute to colorectal cancer (CRC) susceptibility. A hospital-based case-control study consisting of 444 patients and 569 controls was conducted to explore the associations between TP53 Arg72Pro and MDM2 T309G and CRC risk in Chinese. The combined effect of TP53 Arg72Pro and MDM2 T309G was significant in a gene dose-response increasing CRC risk (trend test: P?=?0.02). Individuals carrying 3 or more potential risk alleles had 1.78 times risk (95?% CI: 1.13-2.80) to develop CRC compared with individuals without potential risk allele. This increased cancer risk was more pronounced in smokers who carried 3-4 potential risk alleles (OR?=?2.75, 95?% CI: 1.14-6.60) and in young subjects (OR?=?2.05, 95?% CI: 1.08-3.88). The gene-gene interaction between TP53 Arg72Pro and MDM2 T309G may interact in carcinogenesis of CRC in Chinese, especially in smokers, and this kind of interaction is associated with onset age of CRC.     

Relationship between GSTM1 and GSTT1 polymorphisms and schizophrenia: A case–control study in a Tunisian population

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the pathophysiology of schizophrenia. The glutathione S-transferases (GSTs) forms one of the major detoxifying groups of enzymes responsible for eliminating products of oxidative stress. Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes coding for enzymes involved in detoxification. Thus, in this study we investigated the association of glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) gene deletion polymorphisms and schizophrenia in a Tunisian population. A case–control study including 138 schizophrenic patients and 123 healthy controls was enrolled. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). No association was found between the GSTM1 genotype and schizophrenia, whereas the prevalence of the GSTT1 active genotype was significantly higher in the schizophrenic patients (57.2%) than in the controls (45.5%) with (OR = 0.6, IC 0.37–0.99, p = 0.039). Thus, we noted a significant association between schizophrenia and GSTT1 active genotype. Furthermore, the combination of the GSTM1 and GSTT1 null genotypes showed a non-significant trend to an increased risk of schizophrenia. The present finding indicated that GSTT1 seems to be a candidate gene for susceptibility to schizophrenia in at least Tunisian population.     

XPC Lys939Gln and Ala499Val polymorphisms in colorectal cancer susceptibility: a meta-analysis of case–control studies

The XPC Lys939Gln and Ala499Val polymorphisms were likely to be involved with the development of colorectal cancer. However, there had been inconsistent reports of association. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase and Web of Science for relevant articles with a time limit of December 2012. The strength of association between the XPC Lys939Gln and Ala499Val polymorphisms and colorectal cancer susceptibility were assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI). This meta-analysis including six case–control studies evaluated the associations between the two XPC polymorphisms (Lys939Gln, Ala499Val) and colorectal cancer susceptibility. For XPC Lys939Gln, no obvious associations were found for all genetic models [CC vs AA: OR (95 % CI) = 1.12 (0.94–1.32); CA vs AA: OR (95 % CI) = 1.08 (0.94–1.24); the dominant model: OR (95 % CI) = 1.09 (0.97–1.23); the recessive model: OR (95 % CI) = 1.07 (0.92–1.25)]. For XPC Ala499Val, no obvious associations were also not found for all genetic models [TT vs CC: OR (95 % CI) = 0.84 (0.65–1.10); CT vs CC: OR (95 % CI) = 1.00 (0.86–1.15); the dominant model: OR (95 % CI) = 0.98 (0.85–1.12); the recessive model: OR (95 % CI) = 0.87 (0.67–1.12)]. This meta-analysis suggested that both the XPC Lys939Gln and Ala499Val polymorphisms were not risk factors for increasing colorectal cancer.