While the incidence of noncardia GC has declined in most countries, the rates of cardia GC have remained stable or risen in several European countries, Japan, and North America. However, recent data from the Netherlands [2] found that the incidence of cardia GC between 1989 and 2008 remained stable in females and slightly decreased in males. Age-standardized incidence rates are about twice as high in men as in women [1]. This gender difference is consistent across populations with different prevalences
of environmental risk factors. A multifactorial and multistep model of human gastric carcinogenesis is currently accepted, according to which different environmental and genetic factors are involved at different stages in the cancer process. The aim of this article is to review the most relevant information published from April 2012 selleck chemicals llc to May 2013
on the relative contribution of genetic factors and environmental factors in humans. Individual variations in cancer risk have been consistently associated with specific variant alleles on different genes (polymorphisms) Selleck Epacadostat that are present in a significant proportion of the normal population. Single nucleotide polymorphisms (SNPs) in a wide variety of genes may modify the effect of environmental exposure, and these gene-environmental interactions could explain the high variation in the GC incidence observed around the world. Individual genetic susceptibility may be critical in a variety of processes relevant to gastric carcinogenesis, including mucosal protection against H. pylori, an inflammatory response to the infection, carcinogen detoxification and antioxidant protection, DNA repair processes, and cell proliferation 上海皓元医药股份有限公司 ability. Regarding genes involved in the inflammatory response, a meta-analysis based on 18 studies [3] found an association between IL8 promoter−251 AA genotype and GC risk, mainly
in Asian populations and for intestinal-type GC, but only using a codominant model. Another meta-analysis [4] on IL10-1082 promoter polymorphism and GC risk, based on 22 studies, including 4289 GC cases, found a significant negative association (overall OR = 0.049, p < .001). The association was observed in Asians, Caucasians but not in Latin-American populations. A third meta-analysis [5] on LAT (TNF-β) rs909253 GA genotype and GC risk, based on 12 studies including 2074 GC cases, found a positive and significant association in Asian populations. Regarding polymorphisms in DNA repair genes, in a Chinese case–control study [6] including 1125 cases and 1196 controls, the effect of three functional SNPs of XPG (xeroderma pigmentosum group) belonging to the group of nucleotide excision repair genes was investigated. The rs873601A variant was significantly and positively associated with an increase in GC. These results were confirmed in subsequent mRNA expression analyses as well as on subjects from different ethnicities.