title: Fine-mapping markers of lung cancer susceptibility in a sub-region of chromosome 19q13.3 among Chinese.
abstract: Linkage disequilibrium-mapping studies in Caucasians have indicated anassociation of Chr19q13.3 sub-region spanning ERCC2, PPP1R13L, CD3EAP and ERCC1 with several cancers. To refine the region of association and identify potential causal variations among Asians, we performed a fine-mapping study using 32 (39) SNPs in a 71.654kb sub-region. The study included 384 Chinese lung cancer cases and 387 controls. Seven closely situated SNPs showed significant associations with lung cancer risk in five different genetic models of single-locus associations (adjusted for smoking duration). These were PPP1R13L rs1970764 [OR (95% CI) = 1.58 (1.09-2.29), P = 0.014] in a recessive model and PPP1R13L rs1005165 [OR (95% CI) = 1.25 (1.01-1.54), P = 0.036], CD3EAP rs967591 [OR (95% CI) = 1.40 (1.13-1.75), P = 0.0023], rs735482 [OR (95% CI) = 1.29 (1.03-1.61), P = 0.026], rs1007616 [OR (95% CI) = 0.78 (0.61-1.00), P = 0.046], and rs62109563 [OR (95% CI) = 1.28 (1.03-1.59), P = 0.024] in a log-additive model and ERCC1 rs3212965 [OR (95% CI) = 0.70 (0.52-0.94), P = 0.019] in an over-dominant model. Six-haplotype blocks were determined in the sub-region. Using an alternative approach where we performed a haplotype analysis of all significant polymorphisms, rs1970764 was found to be most consistently associated with lung cancer risk. The combined data suggest that the sub-region with the strongest association to lung cancer susceptibility might locate to the 23.173kb from PPP1R13L intron8 rs1970764 to rs62109563 3' to CD3EAP. Limited risk loci and span on lung cancer in this sub-region are initially defined among Asians.
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Jiaoyang
authors.initials: J
authors.lastname: Yin
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Research Centre for The Working Environment, Lerso Parkalle, Copenhagen O, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Liaoning Cancer Hospital, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Yegang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012318:RNA Polymerase I; D012097:Repressor Proteins / Q000235:genetics; D012907:Smoking; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; C119975:POLR1G protein, human; D012318:RNA Polymerase I; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: Chinese; Chr19q13.3; ERCC2 and PPP1R13L and CD3EAP and ERCC1; fine-mapping; lung cancer