ABSTRACT: Knowledge of the lung cancer genome has experienced rapid growth over the past decade. Genome-wide association studies and sequencing studies have identified dozens of genetic variants and somatic mutations implicated in the development of lung cancer in both Chinese and Caucasian populations. With the accumulating evidence, heterogeneities in lung cancer susceptibility were observed in different ethnicities. In this review, the progress on germline-based genetic variants and somatic-based genomic mutations associated with lung cancer and the differences between Chinese and Caucasian populations were systematically summarized. In the analysis of the genetic predisposition to lung cancer, 6 susceptibility loci were shared by Chinese and Caucasian populations (3q28, 5p15, 6p21, 9p21.3, 12q13.13 and 15q25), 14 loci were specific to the Chinese population (1p36.32, 5q31.1, 5q32, 6p21.1, 6q22.2, 6p21.32, 7p15.3, 10p14, 10q25.2, 12q23.1, 13q22, 17q24.3, 20q13.2, and 22q12), and 12 loci were specific to the Caucasian population (1p31.1, 2q32.1, 6q27, 8p21.1, 8p12, 10q24.3, 11q23.3, 12p13.33, 13q13.1, 15q21.1, 20q13.33 and 22q12.1). In the analysis of genomic and somatic alterations, different mutation rates were observed for EGFR (Chinese: 39-59% vs. TCGA: 14%), KRAS (Chinese: 7-11% vs. TCGA: 31%), TP53 (Chinese: 44% vs. TCGA: 53%), CDKN2A (Chinese: 22% vs. TCGA: 15%), NFE2L2 (Chinese: 28% vs. TCGA: 17%), STK11 (Chinese: 4-7% vs. TCGA: 16%), KEAP1 (Chinese: 3-5% vs. TCGA: 18%), and NF1 (Chinese: <2% vs. TCGA: 12%). In addition, frequently amplified regions encompassing genes involved in cytoskeletal organization or focal adhesion were identified only in Chinese patients. These results provide a comprehensive description of the genetic and genomic differences in lung cancer susceptibility between Chinese and Caucasian populations and may contribute to the development of precision medicine for lung cancer treatment and prevention.
