Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).

Abstract

We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

• Authors: H Dean Hosgood 3rd, Minsun Song, Chao Agnes Hsiung, Zhihua Yin, Xiao-Ou Shu, Zhaoming Wang, Nilanjan Chatterjee, Wei Zheng, Neil Caporaso, Laurie Burdette, Meredith Yeager, Sonja I Berndt, Maria Teresa Landi, Chien-Jen Chen, Gee-Chen Chang, Chin-Fu Hsiao, Ying-Huang Tsai, Li-Hsin Chien, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Chung-Hsing Chen, Tsung-Ying Yang, Chih-Liang Wang, Jen-Yu Hung, Chien-Chung Lin, Reury-Perng Perng, Chih-Yi Chen, Kun-Chieh Chen, Yao-Jen Li, Chong-Jen Yu, Yi-Song Chen, Ying-Hsiang Chen, Fang-Yu Tsai, Christopher Kim, Wei Jie Seow, Bryan A Bassig, Wei Wu, Peng Guan, Qincheng He, Yu-Tang Gao, Qiuyin Cai, Wong-Ho Chow, Yong-Bing Xiang, Dongxin Lin, Chen Wu, Yi-Long Wu, Min-Ho Shin, Yun-Chul Hong, Keitaro Matsuo, Kexin Chen, Maria Pik Wong, Dara Lu, Li Jin, Jiu-Cun Wang, Adeline Seow, Tangchun Wu, Hongbing Shen, Joseph F Fraumeni Jr, Pan-Chyr Yang, I-Shou Chang, Baosen Zhou, Stephen J Chanock, Nathaniel Rothman, Qing Lan
• Journal: Human genetics (Hum Genet) Vol. 134 Issue 3 Pg. 333-41 (Mar 2015) ISSN: 1432-1203 [Electronic] Germany
• PMID: 25566987 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Air Pollutants
• Genetic Markers

Topics

• Adenocarcinoma (chemically induced, genetics)
• Adult
• Aged
• Air Pollutants (toxicity)
• Air Pollution, Indoor
• Case-Control Studies
• Female
• Gene-Environment Interaction
• Genetic Markers
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Lung Neoplasms (chemically induced, genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk