title: Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan.
abstract: BACKGROUND
  Many single nucleotide polymorphisms (SNPs) have been found to be associated with oral cancer but the biological interactions through SNPs are seldom addressed. In this study, we focused on the joint effect for SNP combinations of four DNA repair genes, X-ray repair cross-complementing groups (XRCCs) 1-4, involved in major cancer-related pathways.
  
  
  METHODS
  Single nucleotide polymorphism genotyping was determined using by polymerase chain reaction-restriction fragment length polymorphism in this study (case = 103, control = 98). Different numbers of combinational SNPs with genotypes called the pseudo-haplotypes from these chromosome-wide genes were used to evaluate their joint effect on oral cancer risk.
  
  
  RESULTS
  Except for XRCC2 rs2040639-AG, none of these SNPs was found to individually contribute to oral cancer risk. However, for two combined SNPs, the proportion of subjects with oral cancer was significantly higher in the pseudo-haplotype with AG-CC genotypes in rs2040639-rs861539 (XRCC2-XRCC3) compared with those with non-AG-CC genotypes. Similarly, the pseudo-haplotype of rs2040639-rs861539-rs2075685 (XRCC2-XRCC3-XRCC4) and rs2040639-rs861539-rs2075685-rs1799782 (XRCCs 1-4) with specific genotype pattern (AG-CC-TG and CT-AG-CC-TG) among three and four combinational SNPs were significantly associated with oral cancer. After controlling for age, gender, smoking, drinking, and betel nut chewing, the estimated odds ratio of oral cancer were 2.45, 5.03, and 10.10 for two, three and four specific SNP combinations, respectively, comparing these specific pseudo-haplotypes to their corresponding non-pseudo-haplotypes.
  
  
  CONCLUSIONS
  We have identified the potential combined XRCCs 1-4 SNPs with genotypes that were associated with oral cancer risk and may have an impact on identification of a high-risk population.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, and School of Dentistry, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Yen
authors.forename: Shyun-Yeu
authors.initials: SY
authors.lastname: Liu
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: Hung-Fu
authors.initials: HF
authors.lastname: Tseng
authors.forename: Li-Yeh
authors.initials: LY
authors.lastname: Chuang
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Yang
authors.forename: Ying-Chu
authors.initials: YC
authors.lastname: Lin
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Wen
authors.forename: Wei-Fan
authors.initials: WF
authors.lastname: Chiang
authors.forename: Chang-Hsuan
authors.initials: CH
authors.lastname: Ho
authors.forename: Hsiang-Chi
authors.initials: HC
authors.lastname: Chen
authors.forename: Shaio-Ting
authors.initials: ST
authors.lastname: Wang
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C113187:XRCC2 protein, human; C101467:XRCC4 protein, human