Oncotarget

Research Papers:

Fine-mapping markers of lung cancer susceptibility in a sub-region of chromosome 19q13.3 among Chinese

Jiaoyang Yin _, Huiwen Wang, Ulla Vogel, Chunhong Wang, Yegang Ma, Wei Hou, Ying Zhang, Li Guo and Xinxin Li

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Oncotarget. 2016; 7:60929-60939. https://doi.org/10.18632/oncotarget.9279

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Abstract

Jiaoyang Yin1, Huiwen Wang1, Ulla Vogel2, Chunhong Wang1, Yegang Ma3, Wei Hou4, Ying Zhang1, Li Guo1 and Xinxin Li1

1 Key Laboratory of Environment and Population Health of Liaoning Education Ministry (Shenyang Medical College), Shenyang, Liaoning Province, People’s Republic of China

2 National Research Centre for The Working Environment, Lerso Parkalle, Copenhagen O, Denmark

3 Department of Thoracic Surgery, Liaoning Cancer Hospital, Shenyang, Liaoning Province, People’s Republic of China

4 Department of Pathology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, People’s Republic of China

Correspondence to:

Jiaoyang Yin, email:

Keywords: Chr19q13.3, ERCC2 and PPP1R13L and CD3EAP and ERCC1, fine-mapping, lung cancer, Chinese

Received: December 31, 2015 Accepted: April 19, 2016 Published: May 10, 2016

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. 


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