Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours

Abstract

Objective Genome wide association studies (GWAS) of gastric cancer have reported differences in SNP associations for tumor subtypes, particularly when divided by location into the gastric cardia versus the noncardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric noncardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 noncardia cases, and 7548 controls for replication from two Chinese studies and one from Korean. From the GWAS we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer, and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p = 2.77×10−12) and noncardia cancers (p = 3.95×10−21) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77–0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric noncardia cancer risk (p = 2.50 ×10−8), with OR (95% CI) of 1.18 (1.12–1.26), but there was only a nominal association for cardia cancer (p = 1.47×10−2). We also confirmed a previously reported association for rs4072037 in MUC1 with p = 6.59×10−8 for total GC and similar estimates for cardia and noncardia cancers. Three SNPs in PSCA previously reported to be associated with gastric noncardia cancer showed no apparent association for cardia cancer. Conclusion Our results suggest that associations for SNPs with gastric cancer show some different results by tumor location in the stomach.

Germline genetic variants were interactively associated with somatic alterations in gastric cancer

“…Gastric cancer risk SNPs were extracted from the original gastric cancer GWAS studies in GWAS Catalog 5, 6, 7, 8, 9, 10, 27. Only 1 SNP was remained when multiple variants were in linkage disequilibrium (LD, r 2  ≥ .8), and the minor‐allele frequency (MAF) should be greater or equal than .05.…”

“…Many genetic variations, most of which are single nucleotide polymorphisms (SNPs), have been detected over the past years by the genome‐wide association studies (GWAS) of gastric cancer 4. These common susceptibility loci included 1q22 ( MUC1 ), 3q13.32 ( ZBTB20 ), 5p13.1 ( PRKAA1 ), 5q14.3 ( lnc‐POLR3G‐4 ), 6p21.1 ( UNC5CL ), 8q24 ( PSCA ), and 10q23 ( PLCE1 ) 5, 6, 7, 8, 9, 10…”

Genome-Wide Association Studies and Epigenome-Wide Association Studies Go Together in Cancer Control

“…Chromosome locus 8q24 was reported to be associated with different cancers including gastric cancer [55], and SNP rs4733616 was specifically associated with gastric cancer. Gastric cancer GWAS facilitated the identification of two tumor subtypes -gastric cardia and gastric noncardia -in a population study [101]. In another independent study, PSCA rs2294008 was found to be associated with increased risk of gastric cancer and decreased risk of duodenal cancer [58].…”

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology

“…52 Cervical cancer, 53,54 oral cancer, 55,56 and head and neck cancers 57,58 have one common feature of the presence of HPV. 53,[55][56][57][58][59][60] Almost all patients with cervical cancer have HPV, whereas this virus is present in most of oral cancer cases and few head and neck cancer cases. More than 100 strains of HPV have been reported to date, although 2 strains, HPV16, and HPV18, are the most virulent among all strains.…”