Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA)
Journal
Human Genetics
Journal Volume
134
Journal Issue
3
Pages
333-341
Date Issued
2015
Author(s)
Hosgood H.D.
III, Song M.
Hsiung C.A.
Yin Z.
Shu X.-O.
Wang Z.
Chatterjee N.
Zheng W.
Caporaso N.
Burdette L.
Yeager M.
Berndt S.I.
Landi M.T.
Chen C.-J.
Chang G.-C.
Hsiao C.-F.
Tsai Y.-H.
Chien L.-H.
Huang M.-S.
Su W.-C.
Chen Y.-M.
Chen C.-H.
Yang T.-Y.
Wang C.-L.
Hung J.-Y.
Lin C.-C.
Perng R.-P.
Chen C.-Y.
Chen K.-C.
Li Y.-J.
Chen Y.-S.
Chen Y.-H.
Tsai F.-Y.
Kim C.
Seow W.J.
Bassig B.A.
Wu W.
Guan P.
He Q.
Gao Y.-T.
Cai Q.
Chow W.-H.
Xiang Y.-B.
Lin D.
Wu C.
Wu Y.-L.
Shin M.-H.
Hong Y.-C.
Matsuo K.
Chen K.
Wong M.P.
Lu D.
Jin L.
Wang J.-C.
Seow A.
Wu T.
Shen H.
Fraumeni J.F.
Jr.
Chang I.-S.
Zhou B.
Chanock S.J.
Rothman N.
Lan Q.
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. ? 2015, Springer-Verlag Berlin Heidelberg (outside the USA).
SDGs
Other Subjects
coal; fuel; HLA antigen class 2; air pollutant; genetic marker; adult; air pollution; Article; cancer risk; cancer susceptibility; controlled study; cooking; female; genetic association; genetic variability; genotype environment interaction; heating; household; household air pollution; human; lung cancer; major clinical study; middle aged; oncogene; priority journal; single nucleotide polymorphism; smoking; TP63 gene; adenocarcinoma; aged; air pollutant; case control study; chemically induced; genetic marker; genetic predisposition; genetics; genome-wide association study; indoor air pollution; lung tumor; risk; toxicity; Adenocarcinoma; Adult; Aged; Air Pollutants; Air Pollution, Indoor; Case-Control Studies; Female; Gene-Environment Interaction; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lung Neoplasms; Middle Aged; Polymorphism, Single Nucleotide; Risk
Publisher
Springer Verlag
Type
journal article