A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population

Abstract

Lung adenocarcinoma is the most common histological type of lung cancer, and its incidence is increasing worldwide. To identify genetic factors influencing risk of lung adenocarcinoma, we conducted a genome-wide association study and two validation studies in the Japanese population comprising a total of 6,029 individuals with lung adenocarcinoma (cases) and 13,535 controls. We confirmed two previously reported risk loci, 5p15.33 (rs2853677, P(combined) = 2.8 × 10(-40), odds ratio (OR) = 1.41) and 3q28 (rs10937405, P(combined) = 6.9 × 10(-17), OR = 1.25), and identified two new susceptibility loci, 17q24.3 (rs7216064, P(combined) = 7.4 × 10(-11), OR = 1.20) and 6p21.3 (rs3817963, P(combined) = 2.7 × 10(-10), OR = 1.18). These data provide further evidence supporting a role for genetic susceptibility in the development of lung adenocarcinoma.

Associations between 25 Lung Cancer Risk–Related SNPs and Polycyclic Aromatic Hydrocarbon–Induced Genetic Damage in Coke Oven Workers

“…We included common SNPs (MAF > 0.05) identified from published GWAS for lung cancer risk in Asians (3,(22)(23)(24)(25)(26)(27)(28)(29), with the exception of one research project published after our experiment was finished (30). Considering the ethnic differences, the SNPs restricted to nonAsians were ignored.…”

An Overview of Genetic Polymorphism and Lung Cancer Risk

“…TERT protein functions in telomere replication and maintenance and promotes epithelial cell proliferation [24]. The risk allele frequency of the TERT SNP rs2736100 is similar among various ethnic populations, and associations have been detected in Europeans, Americans, and Asians [9][10][11][12][13][14]23]. According to a recent meta-analysis of various lung cancer types, this SNP is more strongly associated with ADC than with SQC or SCC [25].…”

“…Several studies report that three chromosomal loci, 15q24-25.1, 5p15.33, and 6p21, are associated with lung cancer risk in European and American populations [7][8][9][10][11][12][13][14], while four, 3q28, 5p15.33, 6p21, and 17q24.2, are associated with ADC risk in Japanese and/or Korean populations [10,11]. In addition, loci at 5q32, 10p14, 13q12.12, 20q13.2, and 22q12.2 are associated with lung cancer risk in the Chinese population [12,15] and loci at 10q25 and 6p21 are associated with susceptibility to lung cancer in females who have never smoked in the Asian population [16].…”

“…Smoking is more weakly associated with the development of ADC than with the development of SCC and SQC [6], indicating that the mechanisms of carcinogenesis differ among the histological types. Several Genome-Wide Association Studies (GWAS) report that inherited genetic factors (i.e., genetic polymorphisms) increase the risk of lung cancer [7][8][9][10][11][12][13][14]. Based on the results of meta-analyses and subgroup analyses, these genetic factors may have different effect sizes with respect to lung cancer risk depending on the population, smoking status, and histological type.…”

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).…”