title: Whole-genome sequencing of asian lung cancers: second-hand smoke unlikely to be responsible for higher incidence of lung cancer among Asian never-smokers.
abstract: Asian nonsmoking populations have a higher incidence of lung cancer compared with their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories of either all the never-smokers or all the smokers or ex-smokers. In addition, nearly one third of the ex-smokers and smokers classified with the never-smoker-like cluster. The somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C>T.A being predominant in smokers. We found EGFR and TP53 to be the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among the 16 never-smokers, 69% had an EGFR mutation compared with 29% of 14 smokers/ex-smokers. Asian never-smokers had lung cancer signatures distinct from the smoker signature and their mutation profiles were similar to European never-smokers. The profiles of Asian and European smokers are also similar. Taken together, these results suggested that the same mutational mechanisms underlie the etiology for both ethnic groups. Thus, the high incidence of lung cancer in Asian never-smokers seems unlikely to be due to second-hand smoke or other carcinogens that cause oxidative DNA damage, implying that routine EGFR testing is warranted in the Asian population regardless of smoking status.
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Vidhya G
authors.initials: VG
authors.lastname: Krishnan
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ebert
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Ting
authors.affiliation: Medical Oncology, Mount Elizabeth Medical Centre, Mount Elizabeth, Singapore. Medical Oncology, Tan Tock Seng Hospital, Singapore, Singapore; Medical Oncology, National University Hospital, Singapore, Singapore;
authors.forename: Elaine
authors.initials: E
authors.lastname: Lim
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Swee-Seong
authors.initials: SS
authors.lastname: Wong
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Audrey S M
authors.initials: AS
authors.lastname: Teo
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Yong G
authors.initials: YG
authors.lastname: Yue
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Hui-Hoon
authors.initials: HH
authors.lastname: Chua
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Ma
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Gary S L
authors.initials: GS
authors.lastname: Loh
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore. ngpc4@gis.a-star.edu.sg tanbop@gis.a-star.edu.sg hillmer@gis.a-star.edu.sg.
authors.forename: Joanna H J
authors.initials: JH
authors.lastname: Tan
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Kun
authors.initials: K
authors.lastname: Yu
authors.affiliation: Genomic Oncology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Shenli
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reinhard
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Daniel S W
authors.initials: DS
authors.lastname: Tan
authors.affiliation: Complete Genomics, Inc., Mountain View, California.
authors.forename: Brock A
authors.initials: BA
authors.lastname: Peters
authors.affiliation: Complete Genomics, Inc., Mountain View, California.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Lincoln
authors.affiliation: Complete Genomics, Inc., Mountain View, California.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Ballinger
authors.affiliation: Complete Genomics, Inc., Mountain View, California.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Laramie
authors.affiliation: Complete Genomics, Inc., Mountain View, California.
authors.forename: Geoffrey B
authors.initials: GB
authors.lastname: Nilsen
authors.affiliation: Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Barber
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore. Genomic Oncology, Duke-NUS Graduate Medical School, Singapore, Singapore. Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore. ngpc4@gis.a-star.edu.sg tanbop@gis.a-star.edu.sg hillmer@gis.a-star.edu.sg.
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore. ngpc4@gis.a-star.edu.sg tanbop@gis.a-star.edu.sg hillmer@gis.a-star.edu.sg.
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ng
mesh_terms: D044466:Asian People / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D014028:Tobacco Smoke Pollution; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors