title: Putative functional variants of XRCC1 identified by RegulomeDB were not associated with lung cancer risk in a Korean population.
abstract: The Encyclopedia of DNA elements (ENCODE) project revealed that nearby or distantly located non-coding DNA regulates the expression of coding genes. RegulomeDB (http://regulome.stanford.edu) is a new database that can be used to predict whether a variant affects transcription factor binding and gene expression. We investigated the association between lung cancer risk and potentially functional polymorphisms of XRCC1 that were selected using RegulomeDB in a Korean population. A total of 185 polymorphisms of XRCC1 were evaluated using RegulomeDB. Strong evidence suggested that 10 polymorphisms, from among the 185, affected XRCC1 expression with scores of 1a-1f that were based on the RegulomeDB scoring system. The rs2854510 polymorphism was rare in Asians (minor allele frequency < 0.05). Eight polymorphisms were in strong linkage disequilibrium (LD). The rs2854509 polymorphism, which was one of the 8 polymorphisms in LD, and rs7248167, which was not in the LD block, were genotyped in 610 lung cancer patients and 607 age- and sex-matched controls. Additionally, four polymorphisms of XRCC1 (rs25487, rs25489, rs1799782, and rs3213245), which were investigated with regard to their association with lung cancer risk in previous studies, were also genotyped. Two polymorphisms (rs2854509 and rs7248167) that were predicted to affect XRCC1 expression based on their RegulomeDB scores were not associated with lung cancer risk (P = 0.31 and 0.93, respectively). When stratified according to age, gender, smoking status, and tumor histology, the two polymorphisms of XRCC1 were not associated with lung cancer risk. Among the four polymorphisms that were previously studied, only rs25489 of XRCC1 was significantly associated with lung cancer risk (dominant model, adjusted odds ratio = 0.61, 95% confidence interval = 0.46-0.83, P = 0.002). Although RegulomeDB is an attractive tool for predicting the regulatory potential of variants, the two polymorphisms that were selected using RegulomeDB were not associated with lung cancer risk.
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.affiliation: Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Deuk Kju
authors.initials: DK
authors.lastname: Jung
authors.affiliation: Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Yi Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Department of Preventive Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Seung Ick
authors.initials: SI
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Thoracic Surgery, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Yangki
authors.initials: Y
authors.lastname: Seok
authors.affiliation: Department of Thoracic Surgery, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Eungbae
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea; Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, Korea. Electronic address: jaeyong@knu.ac.kr.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D030541:Databases, Genetic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human
keywords: Lung cancer; RegulomeDB; XRCC1; polymorphism