Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia

Abstract

A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10−12); however, this association did not achieve genome-wide significance (p < 10−7) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10−8; allelic risk = 0.80, 95% confidence interval (CI) = 0.74–0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67–0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.

TP63 Gene Polymorphisms, Cooking Oil Fume Exposure and Risk of Lung Adenocarcinoma in Chinese Non-smoking Females

“…We have replicated the association between lung adenocarcinoma and SNP rs10937405. The association of this SNP with lung cancer risk was previously reported by a GWAS conducted in Japan and South Korea (Miki et al, 2010), and then be studied in the women who have never smoked tobacco (Hosgood et al, 2012). To be accordant with Hosgood III (Hosgood et al, 2012), TP63 rs10937405 showed a stronger association with lung adenocarcinoma in our population than did TP63 rs4488809.…”

“…The association of this SNP with lung cancer risk was previously reported by a GWAS conducted in Japan and South Korea (Miki et al, 2010), and then be studied in the women who have never smoked tobacco (Hosgood et al, 2012). To be accordant with Hosgood III (Hosgood et al, 2012), TP63 rs10937405 showed a stronger association with lung adenocarcinoma in our population than did TP63 rs4488809. A recent GWAS study among Han Chinese population also found that genetic variation in the TP63 region was associated with lung cancer risk, which showed more pronounced association for rs4488809, although the results were not reported for nonsmoking females (Hu et al, 2011).…”

“…TP63, a nuclear marker of myoepithelial cells, through a variety of mechanisms involved in oncogenesis. There is growing evidence that genetic variation in TP63 may influence susceptibility to lung adenocarcinoma in East Asian populations (Hosgood et al, 2012). Recent genome-wide association study (GWAS) datasets have shown that the single nucleotide polymorphisms (SNPs) of rs10937405 and rs4488809 in TP63 gene on locus 3q28 might be associated with lung adenocarcinoma susceptibility (Miki et al, 2010;Hu et al, 2011).…”

Lung Adenocarcinoma in Never Smokers: Problems of Primary Prevention from Aspects of Susceptible Genes and Carcinogens

“…The hypothesis stated in the original articles on classical genes (20,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) is as follows: exposure of never smokers to ETS resulted in lung AC, hence the genes affected in these cases are the same as those seen in the tobacco-related cases (33)(34)(35)(36). The relative risk of the genes suspected in patients with lung AC exposed to ETS was higher than the frequency of suspected genes in patients with lung AC without exposure to ETS (Table I).…”

Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

“…Future studies analyzing the ethnic group-dependent susceptibility to cancer are required. Several genome-wide association studies (GWASs) on SNPs have identified the genomic loci associated with the risk of lung cancer in Caucasians (26)(27)(28), Europeans (29) and Asians (30)(31)(32)(33)(34). However, the associations of the MDM2 polymorphisms were not investigated in the aforementioned GWASs due to a lack of probes used to discriminate between the polymorphisms (20).…”