***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Inherited polymorphisms in DNA repair genes may contribute to genetic susceptibility to cancer . XPA , XPC and XPD all encode proteins that are part of the nucleotide excision repair pathway . In a nested case-cohort study , we have investigated the occurrence of lung cancer in relation to commonly occurring polymorphisms in XPA , XPC and XPD . Among 54,220 members of a Danish prospect i ve cohort study , 265 lung cancer cases were identified and a sub-cohort comprising 272 individuals was used for comparison . We found that XPA A23 G and XPC Lys939Gln polymorphisms may be risk factors for lung cancer and evidence that positive interactions between the polymorphisms in XPA/XPD and XPC/XPD may occur Current prognostic factors for acute myeloblastic leukemia ( AML ) are not sufficient to accurately predict the group of patients in the intermediate-risk category who will successfully respond to treatment . Distinct patterns of inherited functional genomic polymorphisms might explain part of these heterogeneous prognoses . We used the allelic discrimination method to identify polymorphisms in GSTT1 , SULT1C2 , CDA , SXR ( drug metabolic pathways ) , XPD , XPA , XPG , ERCC1 , TOP2A ( DNA repair ) , VEGF ( angiogenesis ) , and MDR1 ( multidrug resistance ) genes in 110 adult patients with intermediate-risk AML , enrolled in the CETLAM-99 prospect i ve trial . A multivariate prognostic model adjusted for age , white blood cell ( WBC ) count , French-American-British group , cytogenetics , MLL rearrangement , internal t and em duplication of FLT3 ( FLT3-ITD ) , induction courses to achieve complete remission , and germline polymorphisms , was used to detect independent risk factors associated with clinical outcome . This analysis showed an increased risk of refractoriness to chemotherapy in the group of patients with XPA variant alleles ( RR = 14 ; P = .02 ) . In the same model , increased relapse risk was associated with SULT1C2 heterozygosity ( RR = 4.1 ; P = .004 ) , FLT3-ITD ( RR 3.3 ; P = .003 ) , and MDR1 variant alleles ( RR = 2.4 ; P = .02 ) . Adverse prognostic variables for overall survival were XPA ( RR = 3.4 ; P = .02 ) and MDR1 ( RR = 2.1 ; P = .02 ) variant alleles , and WBC count ( RR = 2.1 ; P = .02 ) . These findings might be useful in selecting risk-adapted treatment strategies in intermediate-risk AML Several polymorphisms in DNA repair genes have been reported to be associated with lung cancer risk including XPA ( -4G/A ) , XPD ( Lys751Gln and Asp312Asn ) , XRCC1 ( Arg399Gln ) , APE1 ( Asp148Glu ) and XRCC3 ( Thr241Met ) . As there is little information on the combined effects of these variants , polymorphisms were analyzed in a case-control study including 463 lung cancer cases [ among them 204 adenocarcinoma and 212 squamous cell carcinoma ( SCC ) ] and 460 tumor-free hospital controls .  Odds ratios ( OR ) adjusted for age , gender , smoking and occupational exposure were calculated for the variants alone and combinations thereof . For homozygous individuals carrying the Glu variant of APE1 , a protective effect was found ( OR = 0.77 , CI = 0.51 - 1.16 ) . Individuals homozygous for the variants XPA ( -4A ) ( OR = 1.53 , CI = 0.94 - 2.5 ) , XPD 751Gln ( OR = 1.39 , CI = 0.90 - 2.14 ) or XRCC3 241Met ( OR = 1.29 , CI = 0.85 - 1.98 ) showed a slightly higher risk for lung cancer overall . In the subgroup of adenocarcinoma cases , adjusted ORs were increased for individuals homozygous for XPA ( -4A ) ( OR = 1.62 , CI = 0.91 - 2.88 ) and XRCC3 241Met ( OR = 1.65 ; CI = 0.99 - 2.75 ) . When analyzing the combined effects of variant alleles , 54 patients and controls were identified that were homozygous for two or three of the potential risk alleles [ i.e. the variants in nucleotide excision repair , XPA ( -4A ) and XPD 751Gln , and in homologous recombination , XRCC3 - 241Met ] . ORs were significantly increased when all patients ( OR = 2.37 ; CI = 1.26 - 4.48 ) , patients with SCC ( OR = 2.83 ; CI = 1.17 - 6.85 ) and with adenocarcinoma ( OR = 3.05 ; CI = 1.49 - 6.23 ) were analyzed . Combinations of polymorphisms in genes involved in the same repair pathway ( XPA + XPD or XRCC1 + APE1 ) affected lung cancer risk only in patients with SCC . These results indicate that lung cancer risk is only moderately increased by single DNA repair gene variants investigated but it is considerably enhanced by specific combinations of variant alleles . Analyses of additional DNA repair gene interactions in larger population -based studies are warranted for identification of high-risk subjects Polymorphisms in the XPD and the XPC gene have been associated with a lower DNA repair capacity . We determined the risk of colorectal cancer in association with the four polymorphisms XPA A23 G , XPC Lys939Gln , XPD Lys751Gln and XPD Asp312Asn , and interactions between the polymorphisms and the environmental factors : smoking intensity , intake of alcohol , red meat , processed meat , fish and poultry , fruits and vegetables and dietary fibres , in relation to development of colorectal cancer in a study population of 405 colorectal cancer cases and a comparison group of 810 persons , nested within the Danish prospect i ve cohort , Diet , Cancer and Health , of 57053 cohort members . No association was found between the XPC Lys939Gln , XPA A23 G , XPD Lys751Gln , and XPD Asp312Asn polymorphisms and risk of colorectal cancer . The association of the XPD Lys751Gln polymorphism was statistically significantly different between genders , with a lower risk of colorectal cancer among women carrying the variant allele . We observed a statistically significant interaction between the XPC Lys939Gln polymorphism and consumption of red meat  , with a 3.7-fold increase in colorectal cancer risk per 100 g red meat intake per day among carriers of the homozygous variant , but virtually no effect of red meat intake among carriers of the wild type allele . In the light of the multiple comparisons being made , this result may be a chance finding . The results showed no interaction between the XPD Lys751Gln , XPA A23 G , and XPD Asp312Asn polymorphisms and the environmental factors for the development of colorectal cancer . Overall , the results of the present study indicate that the four polymorphisms are not of major importance in colorectal cancer carcinogenesis Purpose Functional variation in DNA repair capacity through single nucleotide polymorphisms ( SNPs ) of key repair genes is associated with a higher risk of developing various types of cancer . Studies have focused on the nucleotide excision repair ( NER ) and base excision repair ( BER ) pathways . We investigated whether variant alleles in seven SNPs within these pathways increased the risk of  esophageal adenocarcinoma . Methods DNA was extracted from prospect ively collected blood specimens . The sample s were genotyped for SNPs in NER genes  ( XPD Lys751Gln , XPD Asp312Asn , ERCC1 8092C/A , and ERCC1 118C/T ) , and BER genes ( XRCC1 Arg399Gln , APE1 Asp148Glu , and hOGG1 Ser326Cys ) . The presence of variant alleles was correlated with risk of esophageal adenocarcinoma both individually and jointly . Results Variant alleles in NER SNPs XPD Lys751Gln ( AOR = 1.50 , 95 % CI 1.1–2.0 ) , ERCC1 8092 C/A ( AOR = 1.44 , 95 % CI 1.1–1.9 ) , and ERCC1 118C/T ( AOR = 1.42 , 95 % CI 1.0–1.9 ) were individually associated with esophageal adenocarcinoma risk . An increasing number of variant alleles in NER SNPs showed a significant trend with esophageal adenocarcinoma risk ( p = 0.007 ) . Conclusions The presence of variant alleles in NER genes increases risk of esophageal adenocarcinoma . There is evidence of an additive role for SNPs along a common DNA repair pathway . Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways Exposure to estrogens is a likely cause of endometrial cancer , but the means by which estrogens exert this effect are not entirely clear . One hypothesis is that certain estrogen metabolites bind to the DNA , forming bulky adducts that damage the DNA and initiate carcinogenesis . A woman 's reduced capacity to repair such damage may increase her risk of endometrial cancer . We conducted a population -based case-control study in western Washington State to address the role of variation in nucleotide excision repair genes on the risk of endometrial cancer . Case women ( n = 371 ) , ages 50 to 69 years , were diagnosed with invasive endometrial cancer between 1994 and 1999 . Control women ( n = 420 ) were selected using r and om-digit dialing ( ages 50 - 65 years ) and by r and om selection from Health Care Financing Administration data files ( ages 66 - 69 years ) .  Genotyping assays were done for ERCC1 , ERCC2 ( XPD ) , ERCC4 ( XPF ) , ERCC5 ( XPG ) , XPA , and XPC . No appreciable differences between cases and controls were observed in the genotype distributions of ERCC1 ( c8092a and c19007 t ) , ERCC2 ( D312N , K751Q , and c22541a ) , ERCC4 ( R415Q and t30028c ) , or ERCC5 ( D1104H ) . Carriage of at least one variant allele for XPA G23A was associated with decreased risk of endometrial cancer [ odds ratio ( OR ) , 0.70 ; 95 % confidence interval ( 95 % CI ) , 0.53 - 0.93 ] . Carriage of at least one XPC A499V variant allele was associated with a modest decrease in risk ( OR , 0.79 ; 95 % CI , 0.59 - 1.05 ) . Women with variant alleles at both XPC A499V and K939Q had 58 % of the risk of women with no XPC variant alleles ( OR , 0.58 ; 95 % CI , 0.35 - 0.96 ) . Our data suggest that interindividual variation in XPA and XPC influences a woman 's risk of endometrial cancer Polymorphisms in nucleotide excision repair genes have been associated with risk for lung cancer . We examined gene-environment interactions in relation to lung cancer in 430 cases and 790 comparison persons identified within a prospect i ve cohort of 57,053 persons . We included polymorphisms in the XPC , XPA and XPD genes involved in the nucleotide excision DNA repair pathway and analysed possible interactions with smoking and dietary intake of fruit and vegetables in relation to risk for lung cancer . We found that intake of fruit was associated with lower risk for lung cancer only among carriers of the XPA A23 G variant genotype . The incidence rate ratio for lung cancer was 0.60 ( 95 % confidence interval : 0.43 - 0.84 ; p=0.003 ) per 50 % increase in fruit intake . No convincing interactions were detected between the polymorphisms and smoking PURPOSE Polymorphisms in DNA repair genes can influence response to radiotherapy . We analyzed single-nucleotide polymorphisms ( SNP ) in nine DNA repair genes in 108 patients with head- and -neck cancer ( HNSCC ) who had received radiotherapy only .  METHODS AND MATERIAL S From May 1993 to December 2004 , patients with Stage I and II histopathologically confirmed HNSCC underwent radiotherapy .  DNA was obtained from paraffin-embedded tissue , and SNP analysis was performed using a real-time polymerase chain reaction allelic discrimination TaqMan assay with minor modifications . RESULTS Patients were 101 men ( 93.5 % ) and 7 ( 6.5 % ) women , with a median age of 64 years ( range , 40 to 89 years ) . Of the patients , 76 ( 70.4 % ) patients were Stage I and 32 ( 29.6 % ) were Stage II . The XPF/ERCC1 SNP at codon 259 and XPG/ERCC5 at codon 46 emerged as significant predictors of progression ( p = 0.00005 and 0.049 , respectively ) and survival ( 
    Output:
    
This meta- analysis suggests that XPA -4G > A polymorphism is associated with increased lung cancer risk and may be a low-penetrant risk factor in Asian ethnicity for cancer development