Glutathione S-transferases pi 1, alpha 1 and M3 genetic polymorphisms and the risk of hepatocellular carcinoma in humans.
BACKGROUND
Glutathione S-transferases pi1, alpha1 and micro3 are members of an enzymatic superfamily involved in the conjugation and detoxification of carcinogens. Polymorphisms affecting the genes encoding these enzymes may modify their ability to neutralize carcinogens. Our aim was to investigate whether these polymorphisms affect the risk of developing hepatocellular carcinoma in humans.


METHODS
A total of 184 white Spanish patients diagnosed with hepatocellular carcinoma and 248 healthy control subjects from the same ethnic origin were included. GSTA1*B promoter allele, GSTM3*B 3-bp-deleted allele and GSTP1 Ile105Val SNP were identified.


RESULTS
No differences were found between the distribution of the studied polymorphisms, or in the allele frequencies for variant alleles in patients and controls: 0.411 and 0.371 for GSTA1, 0.116 and 0.131 for GSTM3, and 0.285 and 0.309 for GSTP1, respectively. Among patients the GSTP1 mutated allele was more frequent in those drinking more than 50 g ethanol/day (odds ratio: 2.00; 95% confidence intervals: 1.06-3.78). Age at diagnosis, gender, tobacco use and hepatitis B and C viral status did not influence these results.


CONCLUSIONS
We conclude that the studied polymorphisms affecting GSTP1, GSTA1 and GSTM3 genes are probably not related to the risk of developing hepatocellular carcinoma in the studied population.
Ladero
José M
JM
1Universidad Complutense, Service of Gastroenterology, Hospital Clínico San Carlos, C/Martín Lagos s/n, 28040. Madrid. Spain. jladero.hcsc@salud.madrid.org
Martínez
Carmen
C
Fernández
Juana M
JM
Martín
Felipe
F
García-Martín
Elena
E
Ropero
Paloma
P
Villegas
Ana
A
Díaz-Rubio
Manuel
M
Agúndez
José A G
JA
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D007527:Isoenzymes; C483009:GSTM3 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha