title: A specific diplotype defined by PPP1R13L rs1970764, CD3EAP rs967591 and ERCC1 rs11615 and lung cancer risk in a Chinese population.
abstract: Haplotypes defined by multiple loci may be more precise and useful than genotypes in providing risk estimates for particular cancers. Diplotype is defined as a specific combination of two haplotypes. A Chinese case-control analysis comprising 370 cases and 388 controls was conducted to evaluate the effects of the high-risk diplotype predefined as PPP1R13L rs1970764(AA)-CD3EAP rs967591(GG)-ERCC1 rs11615(AA) among Caucasians and three SNPs alone or other haplotypes combined for lung cancer risk. Both the variant G-allele of PPP1R13L rs1970764 and the variant A-allele of CD3EAP rs967591 were significantly over-represented among cases (P=0.03 and P=0.002, respectively). The variant GG-homozygotes of PPP1R13L rs1970764 had increased risk [GG versus AA: adjusted OR (95% CI)=1.30 (1.04-1.62), P=0.02]. The carriers of variant A-allele of CD3EAP rs967591 also presented increased risk [AA versus GG: adjusted OR (95% CI)=1.40 (1.12-1.75), P=0.004; AG versus GG: adjusted OR (95% CI)=1.47 (1.05-2.07), P=0.03 and AG+AA versus GG: adjusted OR (95% CI)=1.26 (1.07-1.48), P=0.005]. Interaction between CD3EAP rs967591 and smoking duration was observed (P=0.003). Only haplotype 1 (the common haplotype) defined as PPP1R13L rs1970764(G)-CD3EAP rs967591(A)-ERCC1 rs11615(G) showed marginally increased risk [OR (95% CI)=1.38 (1.09-1.75), P=0.009] after Bonferroni correction. The frequency of the high-risk diplotype predefined among Caucasians was 1% in controls and no significant evidence of the diplotype distribution between cases and controls was detected in present study. In conclusion, we found that variant alleles of PPP1R13L rs1970764 and CD3EAP rs967591 may contribute to risk factors of lung cancer, but the high-risk diplotype predefined among Caucasians was rare and the diplotype is unlikely to confer lung cancer risk in a Chinese population.
authors.affiliation: Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang 110034, Liaoning Province, People's Republic of China. yinjyf@yahoo.com.cn
authors.forename: Jiaoyang
authors.initials: J
authors.lastname: Yin
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Yegang
authors.initials: Y
authors.lastname: Ma
authors.forename: Huiwen
authors.initials: H
authors.lastname: Wang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.forename: Duohong
authors.initials: D
authors.lastname: Liang
authors.forename: Li
authors.initials: L
authors.lastname: Yue
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012318:RNA Polymerase I; D012097:Repressor Proteins / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
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