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.