title: Polymorphisms in cancer-related pathway genes and lung cancer.
abstract: We evaluated the associations between potentially functional variants in a comprehensive list of cancer-related genes and lung cancer in a Korean population.A total of 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes involved in carcinogenesis were evaluated using an Affymetrix custom-made GeneChip in 610 nonsmall cell lung cancer patients and 610 healthy controls. A replication study was conducted in an independent set of 490 cases and 486 controls. 68 SNPs were significantly associated with lung cancer in the discovery set and tested for replication.Among the 68 SNPs, three SNPs (corepressor interacting with RBPJ 1 (CIR1) rs13009079T>C, ribonucleotide reductase M1 (RRM1) rs1465952T>C and solute carrier family 38, member 4 (SLC38A4) rs2429467C>T) consistantly showed significant associations with lung cancer in the replication study. In combined analysis, adjusted odds ratio for CIR1 rs13009079T>C, RRM1 rs1465952T>C and SLC38A4 rs2429467C>T were 0.69, 0.71 and 0.73, respectively (p=4×10-5, 0.01 and 0.001, respectively) under the dominant model. The relative mRNA expression level of CIR1 was significantly associated with rs13009079T>C genotypes in normal lung tissues (ptrend=0.03).These results suggest that the three SNPs, particularly CIR1 rs13009079T>C, may play a role in the pathogenesis of lung cancer.
authors: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea Dept of Internal Medicine, Kyungpook National University, Daegu, Korea Both authors contributed equally.
authors: Shin Yup
authors: SY
authors: Lee
authors: Dept of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Korea Dept of Cell and Matrix Research Institute, Kyungpook National University, Daegu, Korea Both authors contributed equally.
authors: Hyo-Gyoung
authors: HG
authors: Kang
authors: Dept of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Korea Dept of Cell and Matrix Research Institute, Kyungpook National University, Daegu, Korea.
authors: Jin Eun
authors: JE
authors: Choi
authors: Dept of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Korea BK21 Plus KNU Biomedical Convergence Program, Dept of Biomedical Science, Kyungpook National University, Daegu, Korea.
authors: Deuk Kju
authors: DK
authors: Jung
authors: Dept of Biostatistics Center, Kyungpook National University, Daegu, Korea.
authors: Won Kee
authors: WK
authors: Lee
authors: D&P Biotech, Inc., Daegu, Korea.
authors: Hyun Chul
authors: HC
authors: Lee
authors: Dept of Internal Medicine, Kyungpook National University, Daegu, Korea.
authors: So Yeon
authors: SY
authors: Lee
authors: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea Dept of Internal Medicine, Kyungpook National University, Daegu, Korea.
authors: Seung Soo
authors: SS
authors: Yoo
authors: Dept of Internal Medicine, Kyungpook National University, Daegu, Korea.
authors: Jaehee
authors: J
authors: Lee
authors: Dept of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
authors: Yangki
authors: Y
authors: Seok
authors: Dept of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
authors: Eung Bae
authors: EB
authors: Lee
authors: Dept of Internal Medicine, Kyungpook National University, Daegu, Korea.
authors: Seung Ick
authors: SI
authors: Cha
authors: Dept of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Korea.
authors: Sukki
authors: S
authors: Cho
authors: Dept of Internal Medicine, Kyungpook National University, Daegu, Korea.
authors: Chang Ho
authors: CH
authors: Kim
authors: D&P Biotech, Inc., Daegu, Korea.
authors: Myung Hoon
authors: MH
authors: Lee
authors: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea Dept of Internal Medicine, Kyungpook National University, Daegu, Korea Dept of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Korea jaeyong@knu.ac.kr.
authors: Jae Yong
authors: JY
authors: Park
mesh_terms: D000368:Aged; D026924:Amino Acid Transport System A / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics; D056910:Republic of Korea; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D026924:Amino Acid Transport System A; C117385:CIR1 protein, human; D012097:Repressor Proteins; C507352:SLC38A4 protein, human; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase