Lys751Gln Polymorphism Research Articles

XPD Asp312Asn polymorphism is a risk factor for prostate cancer

The association between Asp312Asn and Lys751Gln polymorphisms of Xeroderma pigmentosum Group D (XPD) and prostate cancer risk are still inconclusive. For better understanding of the effects of these two polymorphisms on prostate cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case-control studies investigating such association. The strength of association between these two polymorphisms and prostate cancer risk was assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI). A total of seven case-control studies were identified, among which five studies (1,257 cases and 1,956 controls) were eligible for Asp312Asn polymorphism and six studies (1,451 cases and 2,375 controls) were eligible for Lys751Gln polymorphism. Asp312Asn polymorphism was associated with an increased risk of prostate cancer in additive and recessive genetic models (additive model: OR = 1.68, 95 % CI = 1.28-2.22, P = 0.00; recessive model: OR = 1.65, 95 % CI = 1.27-2.15, P = 0.00). In the subgroup analysis, Asp312Asn polymorphism was associated with an increased risk of prostate cancer among Asians in all three genetic models (additive model: OR = 2.09, 95 % CI = 1.39-3.14, P = 0.00; dominant model: OR = 1.49, 95 % CI = 1.12-1.98, P = 0.01; recessive model: OR = 1.93, 95 % CI = 1.31-2.83, P = 0.00). However, no significant associations were found between Lys751Gln polymorphism and prostate cancer risk in the overall analyses or the subgroup analyses by ethnicity. The results of this meta-analysis indicate that the XPD Asp312Asn polymorphism is a risk factor for prostate cancer development.

Poly (AT) polymorphism in the XPC gene and smoking enhance the risk of prostate cancer in a low-risk Chinese population

We investigated two polymorphisms of xeroderma pigmentosum complementary group C (XPC) in 202 subjects with prostate cancer (PCa) and 221 healthy controls in a Chinese Han population. Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. Our results indicated that smoking is associated with an increased risk for PCa (odds ratio [OR]: 1.51; 95% confidence interval [CI]: 1.02-2.22). Subjects carrying the XPC-PAT+/+ genotype exhibited a significantly increased risk for PCa (OR: 2.11; 95% CI: 1.12-3.99). The combined subjects with either the PAT+/+ or PAT+/- genotype also exhibited a 1.54-fold increased risk associated with PCa (OR: 1.54; 95% CI: 1.04-2.26). Moreover, smokers with PAT+/- or PAT+/+ had a higher risk for PCa (OR: 1.98; 95% CI: 1.08-3.64; P = 0.026 and OR: 3.56; 95% CI: 1.45-8.76; P = 0.004, respectively) compared with never smokers with the PAT-/- genotype. Analyses of the XPC Lys939Gln polymorphism did not show an association with PCa risk. Our findings support the hypothesis that XPC-PAT polymorphisms may contribute to the risk of developing PCa. More important, an elevated risk of PCa associated with a gene-environment (smoking) interaction was determined in a Chinese population.

ERCC1 and XPD/ERCC2 polymorphisms' predictive value of oxaliplatin-based chemotherapies in advanced colorectal cancer has an ethnic discrepancy: a meta-analysis.

Our purpose is to evaluate the predictive value of the genetic polymorphisms of Excision repair cross-complementing group 1 (ERCC1) and xeroderma pigmentosum group D/excision repair cross-complementing group 2 (XPD/ERCC2) in patients with advanced colorectal cancer receiving oxaliplatin-based chemotherapy, and we performed a meta-analysis in order to obtain a more precise estimation for a more optimizing individual chemotherapy. The relevant cohort studies were identified by searching the electronic databases of MEDLINE, EMBASE, and CNKI. We used ''colorectal,'' ''cancer,'' ''carcinoma,'' ''ERCC1,'' ''XPD or ERCC2,'' ''polymorphism,'' ''oxaliplatin,'' ''treatment,'' or ''chemotherapy'' as key words. Inclusion criteria were patients with advanced colorectal cancer receiving oxaliplatin-based chemotherapy, evaluation of polymorphism of ERCC1 and XPD/ ERCC2, and overall response rate (ORR). In this meta-analysis, a total of seven studies were selected according to the inclusion criteria. Five studies investigated ERCC1 codon 118 polymorphisms and three studies evaluated XPD/ERCC2 codon 751 polymorphisms. For ERCC1 codon C118T polymorphism, the ORR to oxaliplatin-based chemotherapy in patients with C/C wild genotype was 77.27% and it was 69.30% for C/T and T/T variant genotype. The pooled odds ratio (OR) for C/C wild-type vs. C/T and T/T genotype was 1.11 (95% CI, 0.86-1.42; P = 0.42). For XPD/ERCC2 Lys751Gln polymorphism, the response rate was 86.58 and 67.57% in patients with the A/A and either one or two C alleles (A/C or C/C) respectively, and the pooled OR was 1.15 (95% CI, 1.01-1.30; P = 0.03). Furthermore, we chose subgroup analysis in order to find the difference between the Caucasian and Asian ethnicity. The results indicated that Oxaliplatin sensitivity was significantly associated with ERCC1 C118T polymorphism in Asian people. XPD/ERCC2 Lys751Gln polymorphism had the predictive value especially for the patients from the America and Europe.

DNA repair genes XPC, XPG polymorphisms: Relation to the risk of colorectal carcinoma and therapeutic outcome with oxaliplatin‐based adjuvant chemotherapy

Xeroderma pigmentosum complementation group C and G (XPC, XPG) play important roles in DNA damage repairing machinery. Genetic variations in the XPC and XPG may be associated with increased risk for colorectal carcinoma (CRC). In this study, we evaluated the relation between the XPC Lys939Gln, XPG Asp1104His polymorphisms, and CRC susceptibility in a population-based case-control study, which included 1,028 CRC cases and 1,085 controls. Compared with the corresponding wild genotypes, we found that individuals with at least one copy of the XPC Lys939Gln (AC or CC genotype) and XPG Asp1104His (GC or CC genotype) had an increased risk for CRC. In addition, the variant genotypes of the XPC Lys939Gln AC/CC (P = 0.027) or XPG Asp1104His GC/CC (P = 0.003) reduced the elevation of preoperative carcinoembryonic antigen (CEA) level. Moreover a significantly longer progression-free survival (PFS) after Oxaliplatin-based adjuvant chemotherapy was observed in patients with XPG Asp1104His wide-type GG genotype (n = 432, Log-rank test: P = 0.033). Cox proportional hazards analyses demonstrated that variant genotypes of XPG Asp1104His [hazard ratio (HR) = 1.692, 95% confidence interval (95%CI): 1.202-2.383, P = 0.003] as well as pathology grade (HR = 2.545, 95%CI: 2.139-3.030, P < 0.001), and lymph node metastases (HR = 1.851, 95%CI: 1.306-2.625, P < 0.001) were predictive of shorter PFS for the CRC patients with Oxaliplatin-based adjuvant chemotherapy. In conclusion, the current data suggested that XPC Lys939Gln and XPG Asp1104His polymorphisms might contribute to the identification of patients with increased risk for CRC.

DNA repair genes polymorphisms in multiple myeloma: no associationwith XRCC1 (Arg399Gln) polymorphism, but the XRCC4 (VNTR in intron 3 and G-1394T)and XPD (Lys751Gln) polymorphisms is associated with the disease in Turkishpatients

Objective: This study aims to investigate the associationbetween the polymorphisms in DNA repair genes (XPD, XRCC1, and XRCC4)and clinical parameters in patients with multiple myeloma (MM),their effects on prognosis and their roles in susceptibility to MM.Patients and methods: Sixty patients, diagnosed with MM and70 individuals as the healthy control group were included in the study. Genepolymorphisms were detected with the polymerase chain reaction and/or polymerasechain reaction–restriction fragment length polymorphism method. Whenthe genotype frequencies of XPD (Llys751Gln) and XRCC1 (Arg399Gln)genes were examined in the patient and control groups, no significant differencewas detected, while a significant association was found in XRCC4 (VNTRin intron 3 and G-1394T) polymorphisms. A significant association wasfound in the MM patients group for AA genotype and event-free survival (EFS)in terms of XPD (751) gene polymorphism (P = 0·047).When VNTR intron 3 polymorphism was compared for genotype frequency, DD genotypewas found to be significantly low (P = 0·012)in the patient group, whereas GG and TT genotypes were found to be significantlylower in the patient group for the genotype frequency XRCC4 (G-1394T)polymorphism when compared to the control group (P = 0·015, P = 0·010,respectively).Results: These data provide support for the hypothesis thata common variation in the genes encoding XRCC4 DNA repair proteins may contributeto susceptibility to myeloma. These findings require further validation inindependent populations.

Susceptibility ofXPDandRAD51Genetic Variants to Carcinoma of Urinary Bladder in North Indian Population

For the present study, two polymorphisms, xeroderma pigmentosum, complementation group D (XPD) Lys751Gln and RAD51 135G/C were studied with regard to bladder cancer. For XPD Lys751Gln polymorphism, an increased risk of bladder cancer was found to be associated with the Gln variant allele (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.27-2.73), on taking AA (Lys/Lys) as the referent genotype. In males, the XPD 751C (Gln) allele was found to be associated with a significantly increased risk (OR=2.33, 95% CI=1.52-3.56). The inhabitants of rural areas showed a significantly increased risk with the XPD Gln allele (OR=2.59, 95% CI=1.46-4.62) when compared with those of urban areas. In smokers (OR=5.30, 95% CI=2.42-11.68), alcohol drinkers (OR=4.33, 95% CI=2.17-8.70), and nonvegetarians (OR=2.21, 95% CI=1.26-3.87), the XPD Gln allele showed a significantly increased risk toward bladder cancer. For RAD51 135G/C polymorphism, no significant difference was observed in the allelic and genotypic frequencies. Even after stratification, no significant association could be seen. After stratifying histopathologically, the RAD51 CC genotype was associted with decreased risk in subjects having superficial stage (OR=0.51, 95% CI=0.27-0.99) and with those having G2 grade (OR=0.24, 95% CI=0.09-0.62) of bladder cancer. XPD polymorphism may be a predisposing factor, but the same cannot be said for RAD51 gene polymorphism.

XPD Lys751Gln polymorphism and esophageal cancer susceptibility: a meta-analysis of case–control studies

The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and esophageal cancer (EC) remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A comprehensive literature search was conducted to identify all case-control studies of Lys751Gln polymorphism and risk for two main types of EC: esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC). A total of 12 studies were identified to the meta-analysis, including 2,575 cases (1,294 ESCC and 1,281 EADC) and 4,951 controls (1,891 ESCC and 3,060 EADC). Random-effects or fix-effects model was used according to between-study heterogeneity. The odds ratio (OR) for the variant homozygous genotype Gln/Gln of the Lys751Gln polymorphism, compared with the wild type homozygote Lys/Lys, was 1.26, with 95% confidence interval (95% CI) 1.02-1.56, for EADC risk without between-study heterogeneity. When stratified by ethnicity, statistically significantly elevated risk was found among Chinese (Gln/Gln vs. Lys/Lys: OR 2.45, 95% CI = 1.10-5.44). However, no significant associations were found between XPD Lys751Gln polymorphism and EC risk when all studies pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR 1.07, 95% CI = 0.88-1.28; Gln/Gln vs.us Lys/Lys: OR 1.25, 95% CI = 0.92-1.71; dominant model: OR 1.09, 95% CI = 0.90-1.33). In conclusion, this meta-analysis suggests that the Lys751Gln genetic polymorphism may be a potential biomarker of EC susceptibility in Chinese populations. And a study with the larger sample size is needed to further evaluate gene-environment interaction on XPD Lys751Gln polymorphism and EC risk.

Association of ERCC2/XPD polymorphisms and interaction with tobacco smoking in lung cancer susceptibility: a systemic review and meta-analysis

The association of the two ERCC polymorphisms, Asp312Asn and Lys751Gln, with lung cancer risk remains controversial and inconclusive. To better evaluate the potential role of the two polymorphisms and interaction with tobacco smoking in lung cancer susceptibility presented in diverse populations, we have conducted a meta-analysis based on 26 studies from 24 publications which included analyses of Asp312Asn (7121 cases, 8962 controls) and Lys751Gln (8396 cases, 10510 controls) polymorphisms. Overall, significantly elevated lung cancer risk was associated with ERCC2 312Asn allele(homozygous model: OR=1.20[1.05-1.36], P=0.006; recessive model: OR=1.20[1.06-1.35], P=0.004) and 751Gln allele(homozygous model: OR=1.31[1.17-1.46], P<0.00001; heterozygous model: OR=1.11[1.04-1.19], P=0.003; recessive model: OR=1.23[1.11-1.37], P<0.0001; dominant model: OR=1.15[1.08-1.23], P<0.0001). In ethnic subgroup analyses, significantly increased risk was associated with ERCC2 312Asn allele for both Caucasians and Asians, and 751Gln allele for both Caucasians and Latino-Americans. When stratified by smoking status, significantly elevated risk of both polymorphisms for never-smokers was detected (dominant model, OR=1.46[1.09-1.95] and 1.57[1.19-2.08], P=0.01 and 0.002, respectively). In conclusion, this meta-analysis suggests that the two ERCC2 polymorphisms may contribute to lung cancer susceptibility serving as low-penetrance risk factors. Extremely large-scale evidence would be necessary to confirm the effects on ethnically specific populations and gene-environment interactions.

Association of XPC polymorphisms with breast cancer risk

To the Editor, We read with great interest the article by Zheng W et al. [1], which assessed the association between Xeroderma Pigmentosum group C (XPC) polymorphisms and breast cancer risk with a meta-analysis. The results suggested that there was no significant association between either Lys939Gln or Ala499Val polymorphism and breast cancer risk in any genetic model or any subgroup based on ethnicity/source of controls. However, a significant association was observed for PAT ± polymorphism under a recessive model (odds ratio 1.41, 95% confidence interval 1.05–1.89). After carefully reading the article, we noted several methodological issues which should be considered. First, in the ‘‘Publication search’’, they did not state whether there was language restriction for the study identification. In addition, in our opinion, ‘‘Xeroderma Pigmentosum group C’’, the full name of ‘‘XPC’’ also should be used as one of the search terms, to search all relevant potential studies. Second, they did not assess Hardy–Weinberg equilibrium (HWE) in controls of each study. Evidence suggested that deviation from HWE might reflect the presence of genotyping errors, population stratification, and selection bias in the controls [2]. Thus, we assessed HWE in controls of included studies [3–10] in Table 1. Third, in the Table 1 of their study, it is better to present the genotype frequencies of cases and controls to be more readable. In addition, I do not know why they categorized the population in the study by Jorgensen et al. [5] as Caucasian. Indeed, the ethnicity was unknown for this study. In the table 2 of the study, it is also better to provide the number of studies for each subgroup analysis. Fourth, there was only one study with 583 cases and 583 controls, which investigated the association between PAT ± polymorphism and breast cancer risk [10]. Thus, the positive conclusion should be made with caution. At last, we excluded two studies which deviated from HWE in controls for Lys939Gln polymorphism and reassessed the association under a dominant genetic model based on ethnicity (Figs. 1, 2). For Lys939Gln polymorphism, there were 4,064 cases and 4,025 controls; for Ala499Val polymorphism, there were 1,838 cases and 2,007 controls. The association was not statically significant for either Lys939Gln or Ala499Val polymorphism. Since the sample size was relative small, especially in subgroups, further well-designed studies with enough statistical power are required to assess the associations. F. Xu D. Zhong (&) Z. Tang M. Zhou Department of Breast Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410007, China e-mail: zhong_dewu@163.com

Lack of association between XPD Lys751Gln and Asp312Asn polymorphisms and colorectal cancer risk: a meta-analysis of case–control studies

The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln and Asp312Asn polymorphisms and colorectal cancer remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A comprehensive literature search was conducted to identify all case-control studies of Lys751Gln and Asp312Asn polymorphisms on the susceptibility of different tumor site of colorectal cancer (colon, rectum, and colon/rectum cancer). A total of 22 eligible studies were selected for this meta-analysis, including 3,042 cases and 4,627 controls for Lys751Gln and 1,581 cases and 2,846 controls for Asp312Asn. Overall, no significantly elevated colorectal cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (for Lys751Gln polymorphism: Lys/Gln vs. Lys/Lys, OR = 1.01, 95% CI = 0.90-1.14; Gln/Gln vs. Lys/Lys, OR = 1.04, 95% CI = 0.85-1.26; dominant model, OR = 1.03, 95% CI = 0.93-1.15; recessive model, OR = 1.04, 95% CI = 0.87-1.25; and for Asp312Asn polymorphism: Asp/Asn vs. Asp/Asp, OR = 1.11, 95% CI = 0.91-1.35; Asn/Asn vs. Asp/Asp, OR = 1.13, 95% CI = 0.87-1.47; dominant model, OR = 1.09, 95% CI = 0.94-1.26; recessive model, OR = 1.11, 95% CI = 0.88-1.41). And for the additive model, individuals carrying the 751Gln or 312Asn allele were not significantly associated with increased risk to colorectal cancer (OR = 1.02, 95% CI = 0.94-1.11, OR = 1.07, 95% CI = 0.95-1.20). This meta-analysis suggests that XPD Lys751Gln and Asp312Asn polymorphisms may not be associated with colorectal cancer development.

Association of XPC gene polymorphisms with breast cancer risk

To access the association of xeroderma pigmentosum group C (XPC) Lys939Gln (A/C) and Ala499Val (C/T) polymorphisms with breast cancer risk in a Chinese Han population. 173 patients with breast cancer and 171 matched controls in terms of habitation and age (±5 years) were included in this population-based case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was employed to genotyping the Lys939Gln and Ala499Val polymorphisms. Associations of genotypes of Lys939Gln and Ala499Val with breast cancer risk were evaluated using unconditional logistic regression model. Associations between XPC haplotypes and breast cancer risk were estimated by Haplo. Stats package. No significant associations were observed both in individual SNPs and haplotype analyses. However, there was a significant interaction between XPC Lys939Gln polymorphism and menopausal status (P=0.032). The XPC Lys939Gln polymorphism may modulate breast cancer susceptibility jointly with the menopausal status.

DNA repair enzyme polymorphisms and oxidative stress in a Turkish population with gastric carcinoma

Although the developmental stages of gastric carcinoma are still not clear, the constantly generated reactive oxygen and nitrogen species (ROS/RNS) may contribute to the process of carcinogenesis by interacting with DNA. 8-oxoguanine DNA glycosylase-1 (OGG1) is an enzyme involved in base excision repair of 8-oxoguanine that is one of the premutagenic lesions generated by ROS in DNA. The bulky adducts, are recognized and repaired by nucleotid excision repair (NER) enzymes, including xeroderma pigmentosum C and D (XPC, XPD). Eligible 106 gastric cancer patients and 116 cancer-free individuals constituted the study and control groups, respectively. Association between OGG1 Ser326Cys, XPC Lys939Gln, XPD Lys751Gln polymorphisms and the susceptibility tho cancer and the oxidative stress status were evaluated. DNA was extracted from peripheral blood cells and genotypes were determined by using PCR-RFLP. Serum nitric oxide, albumin concentrations, total antioxidant status and Helicobacter pylori IgG were determined. Serum albumin and nitric oxide of cancer patients were lower than that of the controls (P < 0.05). None of the evaluated polymorphisms or Helicobacter pylori IgG seropositivity associated with increased risk of gastric cancer, despite of the increased oxidative stress in cancer patients.

Current evidences on XPC polymorphisms and breast cancer susceptibility: a meta-analysis

Published data on the association between three polymorphisms (Lys939Gln, Ala499Val, and PAT±) of Xeroderma Pigmentosum group C (XPC) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 11 studies including 5,090 cases and 5,214 controls were involved in this meta-analysis. For XPC Lys939Gln polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.00, 95% CI 0.92-1.10; Gln/Gln vs. Lys/Lys: OR = 0.96, 95% CI 0.84-1.09; dominant model: OR = 0.99, 95% CI 0.91-1.08; and recessive model: OR = 0.97, 95% CI 0.86-1.09). In the subgroup analysis by ethnicity or study design, still no obvious associations were found. For XPC Ala499Val polymorphism, also no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Val/Ala vs. Ala/Ala: OR = 0.91, 95% CI 0.79-1.05; Val/Val vs. Ala/Ala: OR = 1.07, 95% CI 0.80-1.44; dominant model: OR = 0.93, 95% CI 0.81-1.06; and recessive model: OR = 1.11, 95% CI 0.84-1.48). For XPC PAT± polymorphism, obvious associations were found for recessive model when all studies were pooled into the meta-analysis (OR = 1.41, 95% CI 1.05-1.89). In conclusion, this meta-analysis suggests that the XPC PAT± polymorphism allele may be a low-penetrant risk factor for developing breast cancer.

Association between XPD Lys751Gln polymorphism and risk of head and neck cancer: a meta-analysis

Several studies have investigated the association between Lys751Gln polymorphism in the xeroderma pigmentosum group D (XPD) gene and risk of head and neck cancer; however, the published results are conflicting. We conducted a meta-analysis that comprised 15 published case-control studies examining the association of head and neck cancer risk with XPD Lys751Gln polymorphism in different populations, based on the data identified in Medline up to November 2010. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association. Overall, significantly elevated head and neck cancer risk was associated with XPD Lys751Gln polymorphism when all studies were pooled into the meta-analysis [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.12, 95%CI = 1.03-1.22, P < 0.01, heterogeneity P = 0.11]. In the subgroup analysis by ethnicity, borderline significantly increased risk was found for Europeans [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.11, 95%CI = 1.00-1.23, P < 0.05]. In conclusion, our meta-analysis demonstrated that XPD Lys751Gln polymorphism could be a prediction marker for risk of head and neck cancer.

XPD and hOGG1 gene polymorphisms in reperfusion oxidative stress

Knee replacement surgery is an ischemia/reperfusion model, as it uses tourniquet applied to the knee area to stop the blood flow during the operation. Fifty patients that were undergoing elective arthroscopic knee surgery were included in our study. Human 8-oxoguanine glycosylase 1 (hOGG1) is an enzyme to repair specific DNA lesions and a good marker of hydroxyl radical damage to DNA. XPD is another DNA repair gene. We investigated the effect of hOGG1 (Ser326Cys) and XPD (Lys751Gln) polymorphisms on the oxidative stress level after reperfusion. To evaluate oxidative stress conditions, we measured 8-hydroxyguanosine and malondialdehyde (MDA) levels. Polymorphism analyses were done by PCR-RFLP; serum 8-hydroxyguanosine and MDA levels were determined by enzyme-linked immunoassay. There were no significant differences between serum MDA and 8-hydroxyguanosine levels in the samples taken before and after tourniquet application; none of these parameters were related with hOGG1 genotypes. However, we observed increased MDA levels after tourniquet application in M allele carriers for the XPD gene; this could mean that M allele carriers are more prone to DNA damage due to oxidative activity.

XPD Lys751Gln polymorphism and esophageal cancer risk: A meta-analysis involving 2288 cases and 4096 controls

To evaluate the association between xeroderma pigmentosum group D (XPD), genetic polymorphism Lys751Gln and esophageal cancer risk. We searched PubMed up to September 1, 2010 to identify eligible studies. A total of 10 case-control studies including 2288 cases and 4096 controls were included in the meta-analysis. Statistical analysis was performed with Review Manage version 4.2. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The results suggested that there is no significant association between XPD Lys751Gln polymorphism and esophageal cancer susceptibility in the overall population. However, in subgroup analysis by histology type, a significant association was found between XPD Lys751Gln polymorphism and esophageal adenocarcinoma (for CC vs AA: OR = 1.25, 95% CI = 1.01-1.55, P = 0.05 for heterogeneity). Our meta-analysis suggested that XPD Lys751Gln polymorphism may be associated with increased risk of esophageal adenocarcinoma.

Assessment of XPD Lys751Gln and XRCC1 T–77C polymorphisms in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy

Polymorphisms in DNA repair genes were thought to represent important determinants of platinum drug efficacy. This study tested whether XPD Lys751Gln and XRCC1 T–77C polymorphisms were associated with survival in platinum-treated patients with advanced non-small-cell lung cancer (NSCLC). In this study, 199 advanced NSCLC patients with platinum-based chemotherapy were recruited. During the median 26.5 months of follow-up, patients with the XPD 751Lys/Lys genotype had a median survival time of 17.0 months (95% CI, 14.5–19.6 months), not much longer than those carried Lys/Gln heterozygote (12.0 months; 95% CI, 3.4–20.6 months; log-rank test, P=0.542). In Cox proportional hazards model, no significant associations were found between XPD Lys751Gln polymorphism and survival. For XRCC1 T–77C polymorphism, the median survival of patients with TC+CC genotype (18 months; 95% CI, 13.5–22.5 months) was similar to those with the TT genotype (16.0 months; 95% CI, 13.3–18.7 months; log-rank test, P=0.399). XRCC1 T–77C polymorphism was not associated with survival in Cox proportional hazards model. Additionally, the analysis for combination of these two polymorphisms also showed no prognostic significance for NSCLC. Our findings indicated that neither XPD Lys751Gln nor XRCC1 T–77C could be genetic determinant for prognosis of advanced NSCLC patients treated with platinum-based chemotherapy.

Ala499Val (C &gt; T) and Lys939Gln (A &gt; C) polymorphisms of the XPC gene: their correlation with the risk of primary gallbladder adenocarcinoma--a case-control study in China

Genetic variations in the gene XPC may be associated with increased risk for gallbladder cancer (GBC). In this study, we detected two non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) in 334 cases of GBC and 329 subjects of hospital-based age- and sex frequency-matched controls in China using a polymerase chain reaction-restriction fragment length polymorphism assay. Allelic association analysis for the two single-nucleotide polymorphisms (SNPs) showed that the risk allele T of Ala499Val was significantly associated with GBC [odds ratio (OR)=1.40, 95% confidence interval (CI): 1.11-1.76, P=0.005), with a population attributive risk of 5.3%. Logistic regression analysis revealed that Ala499Val CT heterozygote (OR=1.56, 95% CI: 1.13-2.14, P=0.002) and TT homozygote (OR=1.93, 95% CI: 1.04-3.55, P=0.048) had a significantly increased risk compared with CC homozygotes. Genetic analysis suggested that either the SNPs directly exert an effect or the linked functional gene impact of the disease trait likely follows an additive or dominant model. Gene interaction analysis demonstrated that the effects of XPC diplotypes (defined as the number of risk genotypes at the two SNP loci) were highly dependent on gallstone. The data from this case-control study indicated that XPC exonic variants contributed to the risk of GBC in this Chinese population.

The association of XPC polymorphisms and tea drinking with colorectal cancer risk in a Chinese population

The xeroderma pigmentosum complementation group C (XPC) is responsible for removal of bulky helix-distorting DNA lesions. Several polymorphisms of XPC gene may modulate the colorectal cancer (CRC) susceptibility. We assessed the association of XPC Lys939Gln (A/C), Ala499Val (C/T), and PAT (-/+) polymorphisms with CRC risk in a population-based case-control study which included 421 CRC patients and 845 controls. For Lys939Gln, the CC genotype was associated with a significantly increased risk of CRC (odds ratio (OR)=1.5; 95% confidence interval (CI)=1.0-2.2) compared with the AA genotype. The subjects with PAT +/+ genotype had a significantly increased risk of CRC (OR=1.5; 95% CI=1.0-2.3), compared with those with PAT-/- genotype. Though no significant association between Ala499Val and CRC risk was observed, we found that individuals carrying the CT+TT genotypes showed a significantly decreased risk of rectal cancer (OR=0.7; 95% CI=0.5-1.0). Additionally, the haplotype C+C was associated with a significantly increased CRC risk (OR=1.3; 95% CI=1.0-1.6), compared with the most common haplotype A-T. Further, individuals with four or more risk alleles exhibited a significantly increased risk of CRC (OR=1.4; 95% CI=1.0-2.0), with a significant gene-dosage effect (P for trend=0.038). Besides, never tea drinking was associated with a significantly increased risk of CRC (OR=2.3; 95% CI=1.7-3.3). Our results suggest that the XPC polymorphisms may modulate CRC susceptibility independently or jointly, and tea drinking has a protective effect on CRC.

XPD Lys751Gln increases the risk of breast cancer

Breast cancer incidence has been on the increase in south Indian women. Polymorphisms in DNA repair genes modify an individual's risk to cancer. XPD (Xeroderma pigmentosum D), a DNA helicase gene involved in nucleotide excision repair and transcription coupled repair, may affect an individual's DNA repair capacity, particularly that of bulky adducts. This case-control study (250 breast cancer cases and 500 healthy controls) aimed to investigate the role of the XPD Lys751Gln polymorphism as a risk factor in the development of breast cancer. Genotyping was performed using the Taq Man allelic discrimination assay. Immunohisto-chemistry was used to quantitate the level of polycyclic aromatic hydrocarbon (PAH) adducts in biopsy samples obtained from the breast cancer patients. Results showed that the XPD Gln/Gln genotype was significantly associated with an increased risk of breast cancer (OR, 1.75; 95% CI 1.02-2.80), particularly in premenopausal female patients (OR, 2.6; 95% CI 1.33-4.79). PAH adduct levels were significantly higher in the cases with breast cancer as compared to the normal breast tissue. This study reveals that XPD may play a role in increasing breast cancer risk particularly in premenopausal females.