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.

Fig. 1

Lung adenocarcinoma risk associated with TP63 rs 10937405 among never-smoking females from Asia, by study. Odds ratios (OR) and 95% confidence intervals (CI) adjusted for age; KUMC Korea University Study, KNUH Kyungpook National University Study, FLCS Fudan Lung Cancer Study, SLCS Shenyang Lung Cancer Study, SWHS Shanghai Women’s Health Cohort Study, SNU Seoul National University Study, CAMSCH Chinese Academy of Medical Sciences Cancer Hospital Study, GELS Genes and Environment in Lung Cancer, Singapore Study, GELAC Genetic Epidemiological Study of Lung Adenocarcinoma (in Taiwan), TLCS Tainjin Lung Cancer Study