Genetic Determinants of Gastric Cancer
Results show that gastric cancer risk is increased by the inheritance of the variant alleles of the metabolic genes SULT1A1 and CYP2E1 *6, especially among smokers and drinkers, respectively. An additional increased risk is conferred by the inheritance of GSTT1 null variant, especially if combined with the NAT2 slow acetylator status. Additionally, the variant allele of MTHFR C677T, associated with inherited low serum folate levels, increases the risk of gastric cancer, especially among those with a low intake of fruit and vegetables. Lastly, I reported that a combination of p53 exon 4 and intron 6 variant alleles protects from gastric cancer, thus confirming recent evidences from other tumour sites. Meta-analyses showed that the c2 variant allele of the phase I enzyme CYP2E1*2 affect the risk of gastric cancer, especially by interacting with a key phase II enzyme as GTSM1, and that the phase II enzyme GSTT1 confer an increased risk of gastric cancer if combined with GSTM1 null. Pooled analysis confirmed the role of folate in gastric carcinogenesis, as individuals with the homozyogous MTHFR C677T variant genotype are at increased risk of gastric cancer especially if carrying a low folate status. In summary, several genetic polymorphisms of genes involved in the cellular metabolism, DNA synthesis and cell cycle regulation were associated with the risk of gastric cancer. MTHFR 677 TT genotype doubled the risk of gastric cancer among subjects carrying a low folate status. The merge of modern genome science with prospective population-based, epidemiological research may provide powerful tools for evaluating possible benefits of public health, preventive nutritional interventions in individuals at risk for gastric cancer.
|Keywords||DNA, gastric cancer, genetics|
|Promotor||Ricciardi, W. , Duijn, C.M. van (Cock)|
|Publisher||Erasmus MC: University Medical Center Rotterdam|
Boccia, S.. (2009, November 18). Genetic Determinants of Gastric Cancer. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/17244