Relationship among metabolizing genes, smoking and alcohol used as modifier factors on prostate cancer risk: exploring some gene-gene and gene-environment interactions.
BACKGROUND
Prostate cancer (PCa) is one of the most common male cancers, but the burden of this disease shows remarkable worldwide variation. The role of susceptibility low penetrance genes and environmental factors in the etiology of (PCa) is unclear, but may involve, in some cases, multiple alleles at multiple loci and environmental factors.


OBJECTIVE
To assess whether CYP1A1, GSTM1, GSTT1 susceptibility genotypes, smoking status and alcohol consumption factors contribute to PCa risk, gene-gene and gene-environment interactions were analyzed.


METHODS
We explored interactions on a multiplicative scale conducting a population-based case-control and a case-only study on 103 incident PCa patients and 132 unrelated controls.


RESULTS
The interaction odds ratios (IOR) for PCa risk were increased in men who had both susceptibility genotypes GST (M1; T1) null and CYP1A1-M1* in a case-control and case-only design (IOR(cc): 1.11; 95% CI: 0.12-10.02; IOR(cc): 6.23; 95%, CI: 0.51-75.89; IOR(co): 2.80; 95% CI: 0.44-17.45 and IORco: 2.65; 95%, CI: 0.30-25.40). No clear evidence for interaction on a multiplicative scale between smoking status, alcohol consumption and genetic polymorphisms in PCa risk was observed.


CONCLUSIONS
Our findings suggest that the interaction between genetic polymorphisms in GST (T1; M1) and CYP1A1-M1* would play a significant role as a modifying factor on PCa risk in Chilean people. However, these preliminary exploratory results should be confirmed in a larger study.
Cáceres
Dante D
DD
Environmental and Occupational Health Division, School of Public Health, University of Chile, Santiago, Chile.
Iturrieta
Jeannette
J
Acevedo
Cristian
C
Huidobro
Christian
C
Varela
Nelson
N
Quiñones
Luis
L
D000428:Alcohol Drinking / Q000009:adverse effects*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase