[Allelic variants of cytochrome P4501A1 (CYP1A1), glutathione S transferase M1 (GSTM1) polymorphisms and their association with smoking and alcohol consumption as gastric cancer susceptibility biomarkers].
BACKGROUND
Gastric cancer (GaC) is the second cause of death by cancer in the world and one of the first causes in Chile. However, the burden of this disease shows remarkable worldwide variation probably explained by environmental and genetic factors. The role of susceptibility low penetrance genes and environmental and dietary factors in the etiology of gastric cancer is not well-known.


OBJECTIVE
To analyze the possible association between CaG susceptibility, genetic (CYP1A1 and GSTM1 polymorphisms) and environmental (tobacco and alcohol) factors.


METHODS
In a case-control study, we included 73 patients with a pathologically diagnosed GaC and 263 controls. DNA was extracted from peripheral blood to detect allele variants for CYP1A1 and GSTM1, using polymerase chain reactions and digestion with restriction enzymes.


RESULTS
There was a clear association of smoking and alcohol ingestion with GaC with odds ratios (OR) of 2.54 (95% confidence intervals (CI) of 1.45-4.46 and OR of 3.36 (95% CI 1.76-6.41), respectively. Polymorphic variants of CYP1A1 and GSTM1 had no association with GaC. However, the m2 variant of CYP1A1 significantly modifies the risk induced by tobacco or alcohol (OR 13.65; 95% CI 3.15-59.05 y 8.37; 95% CI 1.86-37.64, respectively).


CONCLUSIONS
Subjects that carry the m2 allelic variant of CYP1A1 and are exposed to tobacco smoke or alcohol have a significantly higher risk of developing gastric cancer.
Lee
Kuen
K
Laboratorio de Carcinogénesis Química y Farmacogenética, Programa de Farmacología Molecular y Clínica, ICBM, Universidad de Chile, Chile.
Cáceres
Dante
D
Varela
Nelson
N
Csendes D
Atila
A
Ríos R
Horacio
H
Quiñones S
Luis
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000235:genetics; D016022:Case-Control Studies; D002677:Chile; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*
D019363:Cytochrome P-450 CYP1A1; D005819:Genetic Markers; D005982:Glutathione Transferase