ABSTRACT
BACKGROUND: Glutathione S-transferase M1 (GSTM1) and N-acetyltransferase-2 (NAT2) are phase II enzymes involved in the metabolism of xenobiotics and whose polymorphisms have been related to individual cancer risks. PATIENTS AND METHODS: A case-control study was performed including 92 colon, 75 lung and 23 bladder cancer patients and 121 corresponding controls to verify the existence of an association between the main genetic polymorphisms of GSTM1 and NAT2 and the risk to develop cancer. Genomic DNA, isolated from 5 mL whole blood, was used to study GSTM1 and NAT2 polymorphisms using multiplex PCR and a PCR-RFLP technique, respectively. RESULTS: GSTM1 homozygous null genotype was associated with an increased risk of colon cancer, especially in females and in younger patients. For NAT2 gene, the results suggest a role for the low acetylator phenotype in the development of colon and lung cancer, especially in females. In bladder cancer patients two rare NAT2 genotypes were found at a higher frequency compared with all the other groups. CONCLUSION: The results do not suggest a different distribution of GSTM1 and NAT2 polymorphisms in the studied population compared to those reported for other Caucasian populations and warrant further studies in order to evaluate their potential relationship with individual cancer risks.
Subject(s)
Arylamine N-Acetyltransferase/genetics , Colonic Neoplasms/genetics , Glutathione Transferase/genetics , Lung Neoplasms/genetics , Polymorphism, Genetic , Urinary Bladder Neoplasms/genetics , Aged , Base Sequence , Case-Control Studies , DNA Primers , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
Glutathione S-Transferase (GST) is a phase II enzyme and catalyses reactions between glutathione and a variety of electrophilic compounds, including some environmental carcinogens. In man, at least 20 isoenzymatic forms of GST have been identified and many of them show genetically-based individual variability of enzyme activity. The GSTM1 and GSTT1 isoenzymes display several polymorphisms, including a homozygotic deletion, which have been associated with an increased risk for developing neoplastic diseases. There is geographical and ethnic variation in genotype frequencies for both genes. The available data suggest that cancer incidence varies amongst Italian regions, being higher in Northern that in Southern areas, though it is unknown whether this phenomenon is to be attributed to genetic and/or environmental factors. We performed a case-control study to evaluate the GSTM1 and GSTT1 polymorphisms in a series of cancer patients in Basilicata, a Southern Italian region, and in corresponding controls. The results obtained demonstrate that the occurrence of GST polymorphisms in the Basilicata population is not different from other Italian regions and suggest that the population attributable risk associated with these genotypes may be quite high. GSTM1 homozygous null genotype was associated with an increasing risk of cancer, especially in females. The strongest association was with colon and breast cancers. For the GSTT1 gene, the results obtained were suggestive of a decreased risk of cancer associated with the null genotype. Thus, similar studies on these and other susceptibility genes are warranted since they can help to identify susceptible subgroups of people who can be targeted for cancer prevention.
