Comparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations

Abstract

Esophageal squamous cell carcinoma is a major histological type of esophageal cancer, with distinct incidence and survival patterns among races. Although previous studies have characterized somatic mutations in this disease, a rigorous comparison between different patient populations has not been conducted. Here we sequence the samples of 316 Chinese patients, combine them with those from The Cancer Genome Atlas, and perform a comparative analysis between Asian and Caucasian patients. We find that mutated CSMD3 is associated with better prognosis in Asian patients. Applying a robust computational strategy that adjusts for both technical and biological confounding factors, we find that TP53, EP300, and NFE2L2 show higher mutational frequencies in Asian patients. Moreover, NFE2L2 mutations correlate with the allele status of a nearby high-Fst SNP, suggesting their potential interaction. Our study provides insights into the molecular basis underlying the striking racial disparities of this disease, and represents a general computational framework for such a cross-population comparison.

Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers

“…This shared genetic background may confer similarities in cancer incidence and outcomes in populations. Recent large-scale genomic profile studies in individual cancer types, such as prostate (Huang et al, 2017; Petrovics et al, 2015; Powell et al, 2013; Wang et al, 2017), breast (Ademuyiwa et al, 2017; Huo et al, 2017; Keenan et al, 2015; Loo et al, 2011), colon (Guda et al, 2015), lung (Araujo et al, 2015; Campbell et al, 2017; Kytola et al, 2017), gastric (Schumacher et al, 2017), esophageal (Deng et al, 2017), and kidney (Krishnan et al, 2016) cancers have robustly demonstrated that genomic differences in cancers exist among distinct racial and ethnic populations. Consistently, it has been reported that the genetic background of patients may influence specific somatic alterations in cancer genomes during tumorigenesis (Carter et al, 2017).…”

The disparities in gastrointestinal cancer incidence among Chinese populations in Shanghai compared to Chinese immigrants and indigenous non‐Hispanic white populations in Los Angeles, USA

“…All of these epidemiological studies suggest that extrinsic risk factors such as diet and socioeconomic status have a considerable influence on the development of GI cancers. Additionally, a number of genetic studies have shown that nuances in certain genes can also partly explain the observed disparities in GI cancers between populations . Understanding the true etiology of GI cancers is difficult, since it has become increasingly clear that the development of cancer can be considered neither purely genetic nor purely environmental .…”

“…Additionally, a number of genetic studies have shown that nuances in certain genes can also partly explain the observed disparities in GI cancers between populations. [7][8][9] Understanding the true etiology of GI cancers is difficult, since it has become increasingly clear that the development of cancer can be considered neither purely genetic nor purely environmental. 10 However, studies of migrants may provide valuable insight into this field.…”

Enabling population assignment from cancer genomes with SNP2pop

“…Its "oriental" variant with 36% prevalence in East Asians, ALDH2*504Lys, increases risk for alcohol-related liver, colorectal and esophageal cancer by alcohol consumption (16,17). Many other studies have reported prevalent genetic variants in specific population groups which may contribute to the "racial" disparities in occurrence and prognosis (18)(19)(20). Other than these monogenic determinants, polygenic variation models for breast cancer which estimate the combined effect of multiple loci to be highly discriminatory in risk assessment, suggest the benefits of exploring genome-wide risk profiles (21).…”