Sulfotransferase 1A1 polymorphism and gastric cancer risk: a pilot case-control study

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 His213 allele may be important in the development of gastric cancer, with other factors modulating such effect.