Glutathione S-transferase (GST) polymorphisms as risk factors for cancer in a highly homogeneous population from southern Italy.
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.
Sgambato
Alessandro
A
Centro di Ricerche Oncologiche Giovanni XXIII, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome. asgambato@rm.unicatt.it
Campisi
Biagina
B
Zupa
Angela
A
Bochicchio
Annamaria
A
Romano
Gianpiero
G
Tartarone
Alfredo
A
Galasso
Rocco
R
Traficante
Antonio
A
Cittadini
Achille
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics; D008297:Male; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1