- freely available
Int. J. Mol. Sci. 2013, 14(2), 3314-3324; doi:10.3390/ijms14023314
Abstract: The excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and X-ray repair cross-complementing group 1 (XRCC1) genes appear to protect mammalian cells from the harmful effects of ionizing radiation. We conducted a large case-control study to investigate the association of polymorphisms in ERCC1 C118T, ERCC1 C8092A, XRCC1 A194T, XRCC1 A194T, and XRCC3 C241T, with glioma risk in a Chinese population. Five single nucleotide polymorphisms (SNPs) were genotyped, using the MassARRAY IPLEX platform, in 443 glioma cases and 443 controls. Association analyses based on an χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each SNP. For XRCC1 Arg194Trp, the variant genotype T/T was strongly associated with a lower risk of glioma cancer when compared with the wild type C/C (OR = 2.45, 95% CI = 1.43–4.45). Individuals carrying the XRCC1 399A allele had an increased risk of glioma (OR = 1.33, 95% CI = 1.02–1.64). The XRCC3 241T/T genotype was associated with a strong increased glioma risk (OR = 3.78, 95% CI = 1.86–9.06). Further analysis of the interactions of two susceptibility-associated SNPs, XRCC1 Arg194Trp and XRCC3 Thr241Met, showed that the combination of the XRCC1 194T and XRCC3 241T alleles brought a large increase in glioma risk (OR = 2.75, 95% CI = 1.54–4.04). XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 C241T, appear to be associated with susceptibility to glioma in a Chinese population.
Tumors of the central nervous system (CNS) account for about 2% of all cancers, and its morbidity is about 4.2/105 to 5.4/105 people per year, worldwide . Although the incidence of CNS tumors is small, compared with other cancers, these are among the most serious human malignancies, since they affect coordination and the integration of all organic activities. Moreover, as each region of the brain has a vital function, total surgical removal of the organ or tumor, which is used with other cancers, cannot be applied to cure brain tumors . Gliomas are the most common tumors of the CNS. Despite the remarkable progress in the characterization of the molecular pathogenesis of gliomas, these tumors remain incurable and, in most cases, resistant to treatment due to their molecular heterogeneity.
Although many studies have been conducted on the etiology of glioma, it is still not completely understood. The only established environmental risk factors are ionizing radiation and ultraviolet rays, and the low exposure to these types of radiation, in daily life, may explain the low incidence rate of this cancer [3,4]. Both types of radiation cause an accumulation of DNA damage, including oxidative DNA damage, single- and double-strand breaks in DNA chains, and DNA–DNA or DNA–protein cross-links. This DNA damage may lead to tumor development and various cellular dysfunctions . Several complex systems of DNA repair work against DNA damage and prevent mutagenesis, including base excision repair (BER), nucleotide excision repair (NER), double-strand break repair (SSBR), and homologous recombination repair (HRR). BER, NER, and HRR, constitute the main defenses against lesions generated by ionizing radiation, alkylating agents, and reactive oxygen species . The excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1) gene is reported to be a crucial gene in the NER pathway, and ERCC1 polymorphisms can modify the function of NER and, thus, influence the risk of human cancers. X-ray repair cross-complementing groups 1 (XRCC1) polymorphisms facilitate the BER and SSBR processes [7–9]. X-ray repair cross-complementing groups 3 (XRCC3) participates in DNA double-strand break/recombination repair, and likely also participates in HRR .
Several common and putatively functional single nucleotide polymorphisms (SNPs) of ERCC1, XRCC1, and XRCC3 have been identified, of which ERCC1 C118T and ERCC1 C8092A affect ERCC1 mRNA expression, whereas XRCC1 Arg194Trp and XRCC1 Arg399Gln, and XRCC3 Thr241Met are associated with suboptimal DNA repair capacity [9,11], and with an altered risk of several types of cancer [12–15]. Possible associations of polymorphisms in ERCC1 and XRCC1 genes with glioma risk have been examined in European populations with conflicting results [16–19]. However, there have been few reports about the independent and combined roles of ERCC1, XRCC1, and XRCC3 polymorphisms in Chinese populations. Therefore, we conducted a large case-control study to investigate whether there is an association between glioma risk and polymorphisms in these three genes, in a Chinese population.
2. Results and Discussion
A total of 478 cases were asked to participate, of whom 443 were successfully interviewed, and provided 5 mL blood samples, for a participation rate of 92.7%. The mean ages of the cases, and controls, were 50.9 ± 9.6 years and 51.2 ± 9.1 years, respectively (Table 1). There were no significant differences in the ages or sex distributions between the two groups (p > 0.05). However, the glioma patients were more likely to have had a greater exposure history to occupational IR (4.6% vs. 1%, p < 0.05) and a family history of cancer when compared to the controls (21.4 vs. 11.7, p < 0.05). Of the cancer cases, 49.5% were astrocytoma.
The minor allele frequencies, among selected controls of ERCC1 C118T, ERCC1 C8092A, XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met, were consistent with the Minor Allele Frequency (MAF) from the NCBI SNP database (Table 2). ERCC1 C118T, ERCC1 C8092A, XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 Thr241Met, were in line with the Hardy-Weinberg equilibrium in controls (all p values > 0.05).
The genotype distributions of ERCC1 C8092A and XRCC3 Thr241Met were significantly different between cases and controls (Table 3). Associations between these SNPs, and the risk of glioma, were analyzed using conditional logistical regression analysis, with frequency matched by age and sex. For XRCC1 Arg194Trp, the variant genotype T/T was strongly significantly associated with a lower risk of glioma cancer, when compared with the wild-type C/C, with an adjusted OR (95% CI) of 2.45 (1.43–4.45). The XRCC1 194T allele was associated with elevated susceptibility to glioma (OR = 1.76, 95% CI = 1.21–2.06). Individuals carrying the XRCC1 399A allele had a higher risk of glioma (OR = 1.33, 95% CI = 1.02–1.64), as did those with the XRCC3 241T/T genotype (OR = 3.78, 95%CI = 1.86–9.06). The T allele of XRCC3 Thr241Met was significantly associated with a small increased risk of glioma (OR = 1.38, 95% CI = 1.04–1.65).
A further association analysis was conducted to identify the interactions of two susceptibility-associated SNPs, XRCC1 Arg194Trp, and XRCC3 Thr241Met, and their impact on glioma risk. The combination genotype of the XRCC1 194T allele and the XRCC3 241T allele was associated with higher glioma risk (OR = 2.75, 95% CI = 1.54–4.04) (Table 4).
In this case-control study in a Chinese population, we identified the separate and combined effects on the risk of glioma of polymorphisms in ERCC1 C118T, ERCC1 C8092A, XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 Thr241Me. We found that XRCC1 194T/T and XRCC3 241T/T were strongly associated with glioma cancer risk, both individually and in combination.
To the best of our knowledge, our study is the first to describe the associations of these DNA repair gene polymorphisms with glioma risk in a Chinese population. Previous studies have focused on only one or two variants in the ERCC1 and XRCC1 genes, which might not sufficiently capture the effect of susceptibility loci in Chinese glioma patients. A recent Brazilian study, with 80 glioma cases and 100 controls, found that XRCC1 194T/T is associated with a strong increased risk of glioma . Another study conducted in southern China, with 127 glioma cases, showed that the homozygous T/T and heterozygotes C/T variants of XRCC1 codon 194, brought a 2.12-fold and 1.46-fold increased risk of glioma when compared to the homozygous wild-type genotype . Our findings strongly indicate that polymorphisms in XRCC1 Arg194Trp and XRCC3 Thr241Met contribute to glioma susceptibility, and are in line with those of previous studies showing that the XRCC1 194T allele is associated with increased glioma risk [19,20]. However, other studies have obtained conflicting results. One hospital-based study, with 271 cases, reported a non-significant association between the XRCC1 194T allele and glioma risk , and another large sample study with 701 cases also reported a non-significant increased risk of glioma . The inconsistency of these studies may be explained by differences in genetic origin, population background, source of controls, and sample size, or by chance. Alternatively, gene-environment interactions may operate in the pathogenesis of glioma, and thus differences in environmental risk factors may affect glioma risk.
Our study found a slight increased risk of glioma for patients with XRCC1 399Gln/Gln. Several previous studies have also shown that this allele is a risk factor for glioma [20–23]. In a recent study in a Caucasian population, with 373 glioma patients and 365 controls, there was an increased risk of glioma among patients with the XRCC1 399 A/A genotype . Another study reported that this genotype carried a 3.5-fold risk of glioma in a Turkish population . This solidly positive association from above studies seems to be in line with the well-documented functional relevance of this genotype. As far as we know, the XRCC1 Arg399Gln SNP has been a particular research focus, mainly due to its location within the BRCT1 binding domain [24,25], which interacts with Poly(ADP-ribose)polymerase-1(PARP-1), and thus may result in deficient DNA repair. More recently, Taylor et al. showed that the BRCT domain is critical for efficient single-strand break repair and cell survival , and that mutations of the BRCT1 domain of BRCA1 may alter the function of the tumor suppressor gene, and thus increase susceptibility to glioma . XRCC1 Arg399Gln expression is reportedly associated with increased gene expression, as measured by mRNA levels in breast cancer patients . Actually, there was no elevated DNA repair activity in the variant cells. The elevated gene expression might be induced by the variant in a structural region of the gene that theoretically influence the enzyme function but not gene expression
We found that patients with homozygous wild-type genotype XRCC3 had a higher risk of glioma than did those with other genotypes. Similar associations have been identified for other types of cancer, including breast cancer, lung cancer, colorectal cancer, skin melanoma, and gastric cancer [14,15,27–30]. One meta-analysis reported that the XRCC3 241T allele is associated with increased risk for breast cancer in Asian and Caucasian populations . Polymorphisms in DNA repair genes may be associated with differences in repair of DNA damage, and thus influence the risk for developing tumors . An association between cancer risk and XRCC3 Thr241Met was also found in glioma patients in previous studies. A study conducted in a Chinese population, with a large sample size, showed that the XRCC3 241T/T genotype may contribute to the development of glioma , and a Brazilian study reported a strongly increased risk of glioma among patients with the 241T allele . Our data showed that the XRCC3 241T allele had the similar role in previous studies for glioma risk, suggesting that XRCC3 Thr241Met is involved in susceptibility for developing glioma.
The combination of the XRCC1 194T and XRCC3 241T alleles was also strongly associated with glioma in our study. This combination effect could be explained by the additive effect of the two genotypes. This additive effect of XRCC1 and XRCC3 has also been reported in a western population .
3. Experimental Section
3.1. Study Subjects
This case-control study was conducted at the Shengjing Affiliated Hospital of China Medical University. Between October 2007 and January 2012, all hospital patients with newly diagnosed, histologically confirmed primary gliomas, whose first visit fell within two months of initial diagnosis, were asked to participate in the study. Those who consented were interviewed and provided 5 mL blood samples. Controls were selected from among inpatients from the orthopedics, dermatology, and digestive departments; controls had to lack a prior history of cancer, and were frequency matched to cases by age (within 5 years), and sex.
A self-designed questionnaire was used to collect data on demographics and potential risk factors, including smoking, alcohol consumption, and family history of cancer, as well as occupational infrared ray (IR) exposure history.
The research protocol was approved by the ethics committees of the Shengjing Affiliated Hospital of China Medical University, and informed consent was obtained from all recruited subjects.
DNA was extracted from the buffy-coat fractions with the TIANamp blood DNA kit (Tiangen Biotech, Beijing, China). SNP genotyping was performed in a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA). Primers for polymerase chain reaction (PCR) amplification and single base extension (SBE) assays were designed by Sequenom Assay Design 3.1 software (Sequenom, San Diego, CA, USA) according to the manufacturer’s instructions (Table 5). The PCR was performed with 5 ng of genomic DNA, in a reaction volume of 5 μL, using GeneAmp® PCR System 9700 with Dual 384-Well Sample Block Module (Applied Biosystems, Carlsbad, CA, USA). The excess dNTPs was removed by shrimp alkaline phosphatase enzyme solution (Sequenom), and iPLEX® Gold SBE chemistry (Sequenom) was used to perform base extension reaction. The final base extension products were treated with CLEAN resin (Sequenom) to remove salts. A total of 10 nL of reaction solution was dispensed onto a 384 format SpectroCHIP microarray (Sequenom). The MassARRAY Analyzer Compact with ACQUAIRE Module (Sequenom) acquired spectra from the SpectroCHIP, and spectral data were automatically processed and saved to the MassARRAY database. For quality control, genotyping was performed without knowledge of the case/control status of the subjects, and a random sample of 5% of cases and controls was genotyped again by different researchers. The reproducibility was 100%. DNA extraction and SNP genotyping were conducted in the Shengjing Affiliated Hospital of China Medical University.
3.3. Statistical Analysis
All statistical analyses were performed by Stata 8.0 (StataCorp, College Station, USA) and conducted by Dr. W.R. Pan WR. Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were shown as frequencies and percentages. Demographic characteristics were compared between cases and controls by means of a chi-square test and Student’s t test. The Hardy-Weinberg equilibrium (HWE) was checked for controls with the chi-square test. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Because of the low allele frequencies, and relative rarity of the homozygous variant genotypes, we combined the homozygous variant and heterozygous groups for analysis. All comparisons were two-sided, and p < 0.05 was regarded as statistically significant.
In conclusion, we found that the polymorphisms XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 Thr241Met, were significantly associated with glioma cancer susceptibility among Chinese women, and that the combination of XRCC1 194T allele and XRCC3 241T allele was even more strongly associated with elevated glioma risk. Our results support the hypothesis that naturally occurring genetic variation in the X-ray repair cross-complementing group of genes increases susceptibility to glioma.
We thank the great help from Chinese Medical Sciences University, and supports from Natural Science Foundation of Tianjin (08JCYBJC05500).
Conflict of Interest
There is no conflict of interest.
- Parkin, D.M.; Bray, F.; Ferlay, J.; Pisani, P. Global cancer statistics, 2002. CA Cancer J. Clin 2005, 55, 74–108. [Google Scholar]
- Ohgaki, H.; Kleihues, P. Epidemiology and etiology of gliomas. Acta Neuropathol 2005, 109, 93–108. [Google Scholar]
- Sadetzki, S.; Chetrit, A.; Freedman, L.; Stovall, M.; Modan, B.; Novikov, I. Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis. Radiat. Res 2005, 164, 424–432. [Google Scholar]
- Davis, F.; Il’yasova, D.; Rankin, K.; McCarthy, B.; Bigner, D.D. Medical diagnostic radiation exposures and risk of gliomas. Radiat. Res 2011, 175, 790–796. [Google Scholar]
- Pihlajamäki, H.; Hietaniemi, K.; Paavola, M.; Visuri, T.; Mattila, V.M. Surgical versus functional treatment for acute ruptures of the lateral ligament complex of the ankle in young men: A randomized controlled trial. J. Bone Joint Surg. Am 2010, 92, 2367–2374. [Google Scholar]
- Smith, T.R.; Miller, M.S.; Lohman, K.; Lange, E.M.; Case, L.D.; Mohrenweiser, H.W.; Hu, J.J. Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett 2003, 190, 183–190. [Google Scholar]
- Wong, H.K.; Kim, D.; Hogue, B.A.; McNeill, D.R.; Wilson, D.M. DNA damage levels and biochemical repair capacities associated with XRCC1 deficiency. Biochemistry 2005, 44, 14335–14343. [Google Scholar]
- Kubota, Y.; Nash, R.A.; Klungland, A.; Schär, P.; Barnes, D.E.; Lindahl, T. Reconstitution of DNA base excision-repair with purified human proteins: Interaction between DNA polymerase beta and the XRCC1 protein. EMBO J 1996, 15, 6662–6670. [Google Scholar]
- Hanssen-Bauer, A.; Solvang-Garten, K.; Gilljam, K.M.; Torseth, K.; Wilson, D.M.; Akbari, M.; Otterlei, M. The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1. DNA Repair 2012, 11, 357–366. [Google Scholar]
- Tebbs, R.S.; Zhao, Y.; Tucker, J.D.; Scheerer, J.B.; Siciliano, M.J.; Hwang, M.; Liu, N.; Legerski, R.J.; Thompson, L.H. Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene. Proc. Natl. Acad. Sci. USA 1995, 92, 6354–6358. [Google Scholar]
- Taylor, R.M.; Thistlethwaite, A.; Caldecott, K.W. Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair. Mol. Cell. Biol 2002, 22, 2556–2563. [Google Scholar]
- Zipprich, J.; Terry, M.B.; Brandt-Rauf, P.; Freyer, G.A.; Liao, Y.; Agrawal, M.; Gurvich, I.; Senie, R.; Santella, R.M. XRCC1 polymorphisms and breast cancer risk from the New York Site of the Breast Cancer Family Registry: A family-based case-control study. J. Carcinog 2010, 16, 4. [Google Scholar]
- Custódio, A.C.; Almeida, L.O.; Pinto, G.R.; Santos, M.J.; Almeida, J.R.; Clara, C.A.; Rey, J.A.; Casartelli, C. Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas. Genet. Mol. Res 2012, 11, 332–339. [Google Scholar]
- Kiyohara, C.; Horiuchi, T.; Takayama, K.; Nakanishi, Y. Genetic polymorphisms involved in carcinogen metabolism and DNA repair and lung cancer risk in a Japanese population. J. Thorac. Oncol 2012, 7, 954–962. [Google Scholar]
- Liu, Y.; Chen, H.; Chen, L.; Hu, C. Prediction of Genetic Polymorphisms of DNA Repair Genes XRCC1 and XRCC3 in the Survival of Colorectal Cancer Receiving Chemotherapy in the Chinese Population. Hepatogastroenterology 2012, 59, 977–980. [Google Scholar]
- Yang, P.; Kollmeyer, T.M.; Buckner, K.; Bamlet, W.; Ballman, K.V.; Jenkins, R.B. Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer 2005, 103, 2363–2372. [Google Scholar]
- Wrensch, M.; Kelsey, K.T.; Liu, M.; Miike, R.; Moghadassi, M.; Sison, J.D.; Aldape, K.; McMillan, A.; Wiemels, J.; Wiencke, J.K. ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro-Oncology 2005, 7, 495–507. [Google Scholar]
- Kiuru, A.; Lindholm, C.; Heinävaara, S.; Ilus, T.; Jokinen, P.; Haapasalo, H.; Salminen, T.; Christensen, H.C.; Feychting, M.; Johansen, C.; et al. XRCC1 and XRCC3 variants and risk of glioma and meningioma. J. Neurooncol 2008, 88, 135–142. [Google Scholar]
- Custódio, A.C.; Almeida, L.O.; Pinto, G.R.; Santos, M.J.; Almeida, J.R.; Clara, C.A.; Rey, J.A.; Casartelli, C. Analysis of the polymorphisms XRCC1Arg194Trp and XRCC1Arg399Gln in gliomas. Genet. Mol. Res 2011, 10, 1120–1129. [Google Scholar]
- Hu, X.B.; Feng, Z.; Fan, Y.C.; Xiong, Z.Y.; Huang, Q.W. Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma. Asian Pac. J. Cancer Prev 2011, 12, 2981–2984. [Google Scholar]
- Zhou, L.Q.; Ma, Z.; Shi, X.F.; Yin, X.L.; Huang, K.X.; Jiu, Z.S.; Kong, W.L. Polymorphisms of DNA repair gene XRCC1 and risk of glioma: A case-control study in Southern China. Asian Pac. J. Cancer Prev 2011, 12, 2547–2550. [Google Scholar]
- Yosunkaya, E.; Kucukyuruk, B.; Onaran, I.; Gurel, C.B.; Uzan, M.; Kanigur-Sultuybek, G. Glioma risk associates with polymorphisms of DNA repair genes, XRCC1 and PARP1. Br. J. Neurosurg 2010, 24, 561–565. [Google Scholar]
- Liu, Y.; Scheurer, M.E.; El-Zein, R.; Cao, Y.; Do, K.A.; Gilbert, M.; Aldape, K.D.; Wei, Q.; Etzel, C.; Bondy, M.L. Association and interactions between DNA repair gene polymorphisms and adult glioma. Cancer Epidemiol. Biomarkers Prev 2009, 18, 204–214. [Google Scholar]
- Lunn, R.M.; Langlois, R.G.; Hsieh, L.L.; Thompson, C.L.; Bell, D.A. XRCC1 polymorphisms: Effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 1999, 59, 2557–2561. [Google Scholar]
- Zhang, X.; Morera, S.; Bates, P.A.; Whitehead, P.C.; Coffer, A.I.; Hainbucher, K.; Nash, R.A.; Sternberg, M.J.; Lindahl, T.; Freemont, P.S. Structure of an XRCC1 BRCT domain: A new protein-protein interaction module. EMBO J 1998, 17, 6404–6411. [Google Scholar]
- Sterpone, S.; Cozzi, R. Influence of XRCC1 Genetic Polymorphisms on ionizing radiation-induced dna damage and repair. J. Nucleic Acids 2010, 780369:1–780369:6. [Google Scholar]
- Romanowicz-Makowska, H.; Smolarz, B.; Zadrozny, M.; Westfa, B.; Baszczyński, J.; Kokołaszwili, G.; Burzyfiski, M.; Połać, I.; Sporny, S. The association between polymorphisms of the RAD51-G135C, XRCC2-Arg188His and XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland. Eur J. Gynaecol. Oncol 2012, 33, 145–150. [Google Scholar]
- Han, S.; Zhang, H.T.; Wang, Z.; Xie, Y.; Tang, R.; Mao, Y.; Li, Y. DNA repair gene XRCC3 polymorphisms and cancer risk: A meta-analysis of 48 case-control studies. Eur. J. Hum. Genet 2006, 14, 1136–1144. [Google Scholar]
- Zhao, L.; Long, X.D.; Yao, J.G.; Wang, C.; Ma, Y.; Huang, Y.Z.; Li, Y.Q.; Wang, M.F.; Fu, G.H. Genetic polymorphism of XRCC3 codon 241 and Helicobacter pylori infection-related gastric antrum adenocarcinoma in Guangxi Population, China: A hospital-based case-control study. Cancer Epidemiol 2011, 35, 564–568. [Google Scholar]
- Lee, S.A.; Lee, K.M.; Park, S.K.; Choi, J.Y.; Kim, B.; Nam, J.; Yoo, K.Y.; Noh, D.Y.; Ahn, S.H.; Kang, D. Genetic polymorphism of XRCC3 Thr241Met and breast cancer risk: Case-control study in Korean women and meta-analysis of 12 studies. Breast Cancer Res. Treat 2007, 103, 71–76. [Google Scholar]
- Sreeja, L.; Syamala, V.S.; Syamala, V.; Hariharan, S.; Raveendran, P.B.; Vijayalekshmi, R.V.; Madhavan, J.; Ankathil, R. Prognostic importance of DNA repair gene polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln in lung cancer patients from India. J. Cancer Res. Clin. Oncol 2008, 134, 645–652. [Google Scholar]
N = 443
N = 443
|Age (mean ± SD), years||50.9 ± 9.6||51.2 ± 9.1|
|Occupational IR exposure history|
|Family history of cancer|
|Gene name||Single nucleotide polymorphism||Alleles||MAF a||HWE (p value) b Control|
aMinor Allele Frequency;bHardy-Weinberg equilibrium.
|Single nucleotide polymorphism||Cases N = 443||%||Controls|
N = 443
|%||p value||OR a (95% CI)||OR b (95% CI)|
|ERCC1 C118T (rs11615)|
|T/T||193||43.5||211||47.6||0.45||1.0 (Ref.)||1.0 (Ref.)|
|C/T||171||38.6||162||36.6||1.15 (0.85–1.56)||1.32 (0.89–1.67)|
|C/C||79||17.9||70||15.8||1.23 (0.83–1.83)||1.38 (0.91–1.94)|
|C allele||250||56.5||232||52.4||1.18 (0.89–1.55)||1.27 (0.96–1.67)|
|ERCC1 C8092A (rs3212986)|
|G/G||229||51.8||241||54.3||<0.05||1.0 (Ref.)||1.0 (Ref.)|
|G/T||169||38.1||162||36.5||1.10 (0.82–1.47)||1.24 (0.93–1.61)|
|T/T||45||10.1||41||9.2||1.15 (0.71–1.88)||1.30 (0.88–1.93)|
|T allele||214||48.2||202||45.7||1.16 (0.87–1.54)||1.33 (0.98–1.66)|
|XRCC1 Arg194Trp (rs1799782)|
|C/C||301||67.9||327||73.8||0.06||1.0 (Ref.)||1.0 (Ref.)|
|C/T||116||26.1||101||22.9||1.24 (0.91–1.72)||1.36 (0.97–1.83)|
|T/T||27||6||15||3.3||1.98 (1.01–4.03)||2.45 (1.43–4.45)|
|T allele||142||42.6||116||34.8||1.33 (0.98–1.80)||1.76 (1.21–2.06)|
|XRCC1 Arg399Gln (rs25487)|
|G/G||226||51.1||244||55.1||0.4||1.0 (Ref.)||1.0 (Ref.)|
|G/A||190||42.8||178||40.1||1.15 (0.87–1.53)||1.28 (0.97–1.66)|
|A/A||27||6.1||21||4.8||1.39 (0.73–2.66)||1.54 (0.88–2.87)|
|A allele||217||64.9||199||59.6||1.19 (0.90–1.55)||1.33 (1.02–1.64)|
|XRCC3 Thr241Met (rs861539)|
|C/C||217||48.9||234||52.8||<0.05||1.0 (Ref.)||1.0 (Ref.)|
|C/T||198||44.8||200||45.2||1.07 (0.81–1.41)||1.22 (0.96–1.54)|
|T/T||28||6.3||9||2||3.35 (1.49–8.25)||3.78 (1.86–9.06)|
|T allele||226||67.8||209||62.6||1.17 (0.89–1.53)||(1.04–1.65)|
aNot adjusted;bAdjusted for smoking, alcohol drinking, and family history of cancer, as well as occupational infrared ray (IR) exposure history; Ref.: reference.
|Single nucleotide polymorphism||Cases|
N = 443
N = 443
|%||OR (95% CI)||OR (95% CI)|
|XRCC1 Arg194Trp/XRCC3 Thr241Met|
|CC/CC||140||31.6||149||33.6||1.0 (Ref.)||1.0 (Ref.)|
|T allele/CC||77||17.4||85||19.2||1.02 (0.64–1.44)||1.12 (0.78–1.61)|
|CC/T allele||161||36.3||178||40.2||0.98 (0.71–1.37)||1.03 (0.83–1.52)|
|T allele/T allele||65||14.7||31||7.0||2.24 (1.35–3.76)||2.75 (1.54–4.04)|
|Single nucleotide polymorphism||Primer||Sequence||Extension primer|
|ERCC1 C118T (rs11615)||1st-primer||ACGTTGGATGCTAGACCCTAGCAACTCCAG||AGCAACTCCAGGCTAGAGGGCA|
|ERCC1 C8092A (rs3212986)||1st-primer||ACGTTGGATGGCTCACCTGGTGATGTCTT||CTGGTGATGTCTTGTTGATCC|
|XRCC1 Arg194Trp (rs1799782)||1st-primer||ACGTTGGATGCCTAGCAACTCCAGGCTAGA||CTGGTGATGTCTTGTTGATCC|
|XRCC1 Arg399Gln (rs25487)||1st-primer||ACGTTGGATGAGATGCTGGGTGATTGTTGG||GAGTGTGTGGGAGGGGAG|
|XRCC3 Thr241Met (rs861539)||1st-primer||ACGTTGGATGCAACCCTCTGTGAGTGTGTG||GAGTGTGTGGGAGGGGAG|
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