Sistema Gastrointestinal e Digestivo

Abstrato

Five Gastric Cancer-Susceptibility Loci Identified by Genome-Wide Association Studies

Hiroe Ono and Norihisa Saeki

Gastric cancer is one of the most common cancers worldwide, especially in Asia, and ranks fourth in cancer death worldwide. Recently, in order to identify genes related to gastric cancer susceptibility, three genome-wide association studies were conducted using Japanese or Chinese populations, which revealed 5 gastric cancer-susceptibility loci: chromosome 1q22, 3q13.31, 5p13.1, 8q24.3 and 10q23. Further statistical and biological studies unveiled the causal candidate genes for the association in each locus: Mucin 1 (MUC1), encoding a membrane protein, in 1q22; zinc finger and BTB domain containing 20 (ZBTB20), a transcription factor, in 3q13.31; protein kinase, AMP-activated, alpha 1 catalytic subunit (PRKAA1), a ser/thr protein kinase, and/or prostaglandin E receptor 4 (PTGER4), a prostaglandin E2 receptor, and other 3 genes, in 5p13; Prostate stem cell antigen (PSCA), a membrane protein, in 8q24; phospholipase C, epsilon 1 (PLCE1), a phospholipase, in 10q23. Among these genes, MUC1 and PSCA were biologically investigated to obtain some rational for their relation to gastric carcinogenesis; however, the function of the other genes in cancer development is yet to be uncovered. As the genes identified through the genome-wide association studies have a strong potential to open a new door in cancer research, further studies are anticipated to be performed to elucidate their function and molecular pathways for application of the products to the therapy and prevention of gastric cancer.