***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: 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 Several single nucleotide polymorphisms ( SNPs ) affecting DNA repair capacity and modifying cancer susceptibility have been described . We evaluated the association of SNPs Arg194Trp , Arg280His , and Arg399Gln in the X-ray cross-complementing group 1 ( XRCC1 ) and Thr241Met in the X-ray cross-complementing group 3 ( XRCC3 ) DNA repair genes with the risk of brain tumors . The Caucasian study population consisted of 701 glioma ( including 320 glioblastoma ) cases , 524 meningioma cases , and 1,560 controls in a prospect i ve population -based case – control study conducted in Denmark , Finl and , Sweden , and the UK . The studied SNPs were not significantly associated with the risk of brain tumors . The highest odds ratios ( ORs ) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma ( OR = 1.32 ; 95 % confidence interval , CI , 0.97–1.81 ) , glioblastoma ( OR = 1.48 ; 95 % CI , 0.98–2.24 ) , and meningioma ( OR = 1.34 ; 95 % CI , 0.96–1.86 ) . However , in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors : Among others , carriers of both homozygous variant genotypes , i.e. , XRCC1 Gln399Gln and XRCC3 Met241Met , were associated with a three-fold increased risk of glioma ( OR = 3.18 ; 95 % CI , 1.26–8.04 ) and meningioma ( OR = 2.99 ; 95 % CI , 1.16–7.72 ) . In conclusion , no significant association with brain tumors was found for any of the polymorphisms , when examined one by one . Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors Environmental carcinogens contained in air pollution , such as polycyclic aromatic hydrocarbons , aromatic amines or N-nitroso compounds , predominantly form DNA adducts but can also generate interstr and cross-links and reactive oxygen species . If unrepaired , such lesions increase the risk of somatic mutations and cancer . Our study investigated the relationships between 22 polymorphisms ( and their haplotypes ) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases ( bladder cancer , 131 ; lung cancer , 134 ; oral-pharyngeal cancer , 41 ; laryngeal cancer , 47 ; leukaemia , 179 ; death from emphysema and chronic obstructive pulmonary disease , 84 ) . The design was a case-control study nested within a prospect i ve investigation . Among the many comparisons , few polymorphisms were associated with the diseases at the univariate analysis : XRCC1 - 399 Gln/Gln variant homozygotes [ odds ratios ( OR ) = 2.20 , 95 % confidence intervals ( CI ) = 1.16 - 4.17 ] and XRCC3 - 241 Met/Met homozygotes ( OR = 0.51 , 95 % CI = 0.27 - 0.96 ) and leukaemia . The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1 - 399Gln/Gln in lung cancer ( OR = 0.22 , 95 % CI = 0.05 - 0.98 ) , and confirmed an opposite effect ( OR = 2.47 , 95 % CI = 1.02 - 6.02 ) in the leukaemia group . Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia ( OR = 1.28 , 95 % CI = 1.02 - 1.61 ) , bladder cancer ( OR = 1.38 , 95 % CI = 1.06 - 1.79 ) and possibly other cancer risks . Further investigations of the combined effects of polymorphisms within these DNA repair genes , smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process 
    Output:
    
Many of the reported SNPs had diverse association with specific human cancers .
For example , there was a positive association between the OGG1 Ser326Cys variant and gastric and lung cancer , while the XRCC1 Arg399Gln variant was associated with reduced cancer risk .