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. Cancer Res; 74(21);

Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma

“…Earlier studies have demonstrated that LUADs of East Asians exhibit disparate mutational spectra (e.g. more prevalent activating mutations in EGFR ) relative to LUADs from Western (or Caucasian) patients [48,49]. It is reasonable to surmise that mutational differences in AAHs, across patients of different ethnicities, to roughly reflect those we observe in LUADs.…”

No impact of passive smoke on the somatic profile of lung cancers in never-smokers

“…This actually constitutes one of the possible reasons why mutation spectrum is not affected by indirect smoking exposure. These findings are in line with recent observations obtained by whole-genome sequencing [27]. Thus, some other risk factor may be suspected in this setting, such as environmental pollution (including natural radon and atmospheric pollution), occupational exposure, domestic pollution (cooking and heating fumes, or cooking oil), personal history of cancer or respiratory disease, or familial history of cancer supporting the role of genetic factors [2].…”

Modern Treatments in Advanced Non–Small-Cell Lung Cancer: Temporal Trends and Effect on Survival. A French Population-Based Study

“…21 However, the increase in lung cancer incidence in never-smokers is a very controversial issue, with proposed explanations principally being secondhand smoke, other environmental toxins, and genetic polymorphism. 23,24 Moreover, as the proportion of elderly patients increases, aging becomes a risk factor per se, with smoking being degraded as a factor. 25 Histological distribution showed an increase in adenocarcinoma rather than squamous cell carcinoma frequency over time.…”