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HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese.

Abstract：

BACKGROUND:Chromosome 19q13.3 has been identified as one of the regions that associate with cancer risk in previous studies. METHODS:We systematically examined the 70.772kb region comprising four genes on chromosome 19q13.3 among Chinese using the haplotype-tagging SNP (htSNP) approach and the HapMap platform. The study involved 339 lung cancer cases and 358 non-cancer controls. Two htSNPs (rs1046282 and rs735482) captured most of the common haplotypes of CD3EA and the combined effects of sixteen htSNPs provided high coverage of common haplotypes of ERCC2, PPP1R13L, CD3EAP and ERCC1. RESULTS:Both carriers of variant CC genotype [adjusted OR (95% CI)=1.28 (1.02-1.60), P=0.04] and variant C-allele among >20 years' smokers [OR (95% CI)=2.13 (1.24-3.67), P=0.006] for CD3EAP rs735482 were at increased risk of lung cancer. Four haplotype blocks of strong linkage disequilibrium were identified. The haplotype ERCC2 rs3916874(G) and rs238415(C) [OR (95% CI)=1.26 (1.02-1.57), P=0.03] in block 1 and the haplotype PPP1R13L rs4803817(A), CD3EAP rs1046282(T), rs735482(C), ERCC1 rs3212980(A), rs3212964(G) [OR (95% CI)=3.56 (1.55-8.18), P=0.005] in block 3 were associated with lung cancer risk. MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P=0.004-0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk. CONCLUSIONS:HapMap-based study of 19q13.3 identified that genetic variation of CD3EAP and two loci were associated with lung cancer risk and interaction of smoking duration and genetic variants was the strongest predictor of lung cancer risk in a Chinese population.

journal_name

Cancer Epidemiol

journal_title

Cancer epidemiology

authors

Yin J,Vogel U,Wang H,Ma Y,Wang C,Liang D,Liu J,Yue L,Zhao Y,Ma J

doi

10.1016/j.canep.2013.09.016

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

923-9

issue

eissn

1877-7821

issn

1877-783X

pii

S1877-7821(13)00158-6

journal_volume

pub_type

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HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese.