Genome-wide interaction analysis identified low-frequency variants with sex disparity in lung cancer risk

Abstract

There is growing evidence showing that sex disparity in lung cancer risk cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotype from a lung cancer cohort including ~ 47,000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 (OR=0.71, p=4.29x10-8); rs79942605 (OR=2.17, p=2.81x10-8); and rs208908 (OR=0.70, p=4.54x10-8), were identified with different risk effect of lung cancer between men and women. Further eQTL and functional annotation analysis suggested rs208908 affect lung cancer risk through differential regulation of CXADR (Coxsackie Virus And Adenovirus Receptor) gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.

A pilot analysis of circulating cfRNA transcripts for the detection of lung cancer

“…The main risk factor for developing NSCLC is smoking, which is preventable, yet highly prevalent with over a billion smokers around the world [2]. Moreover, smoking, and other environmental pollutants interact with biological factors such as aging and genetic risk variants to increase disease burden [3][4][5][6]. Furthermore, the NSCLC risk has been shown to correlate positively with severity and duration of smoking, and negatively with time since smoking cessation [7,8].…”