Search

Abstract: Susceptibility to gastric cancer may be in part attributable to inter-individual variability in metabolic activation or detoxification of carcinogens, and in this context the polymorphic GSTM1 gene has been extensively studied. Seventeen reports detailing a possible association between GSTM1 deletion and gastric cancer have been published so far. In order to examine the risk of gastric cancer associated with GSTM1 null genotype, a meta-analysis of published case–control studies was undertaken using a random effect model. Two studies were excluded because some data were missing in the results. The principal outcome measure was the odds ratio for the risk of gastric cancer. Pooling all the 15 studies identified, the overall odds ratio of gastric cancer risk associated with GSTM1 deficiency was 1.24 (95% confidence interval, 1.00–1.54). Furthermore, by pooling four studies detailing the possible interaction between GSTM1 status smoking habits and gastric cancer risk, an overall estimate of odds ratio of 2.93 (95% confidence interval, 1.56–5.47) for ever smokers with GSTM1 deficiency compared to non-smokers with GSTM1 normal genotype has emerged. These results suggest that GSTM1 status probably has no effect on the risk of gastric cancer per se, but may modulate tobacco-related carcinogenesis of gastric cancer. Greater attention should therefore be paid to the design of future studies: only well designed population-based control studies considering all the possible confounding risk factors and based on a sample size commensurate with the detection of small genotypic risk may allow a more definitive conclusion. [Copyright &y& Elsevier]

Abstract: Sulfotransferases (SULT) catalyse both the bioactivation and detoxification of a wide range of promutagens and carcinogens. The SULT1A1 gene possesses a G→A polymorphism that results in a Arg to His substitution at codon 213, and the His allele has been shown to have a low activity and thermal stability. To test the hypothesis that individuals carrying the variant allele may be at high risk of gastric cancer, we identified the SULT1A1 Arg213His genotype by a PCR-based RFLP in a preliminary study of 76 gastric adenocarcinoma patients that underwent curative gastrectomy and 260 age and sex-matched controls from a medical centre in Rome. A comprehensive epidemiological interview was conducted on all participants to collect lifestyle data. The prognostic significance of the SULT1A1 Arg213His polymorphism with respect to staging, differentiation and histological type of gastric cancer was also evaluated. The frequencies of His/His in cases and controls were 11.9% (9/76) and 5% (13/260), respectively (P=0.025). After adjusting for substance use, age, gender and physical activity, individuals with His/His showed a 3.32 fold increased risk of developing gastric cancer compared to those with Arg/Arg (95% CI=1.17–9.45). This positive association was more pronounced amongst males, alcohol drinkers, current smokers and consumers of grilled/barbecued meat and, unexpectedly, amongst individuals with a high intake of fruit. A statistically significant association was also found between the diffuse type of gastric cancer and the heterozygous SULT1A1 genotype. Our preliminary findings suggest for the first time that the SULT1A1 His 213 allele may be important in the development of gastric cancer, with other factors modulating such effect. [Copyright &y& Elsevier]