CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer.
Cytochrome P4501A2 (CYP1A2) is a key enzyme for activation of bladder carcinogens. Polymorphisms in the 5'-noncoding promoter region of CYP1A2 gene [mainly -2467T/delT(rs35694136) and -163C/A(rs762551)], are crucial in modifying CYP1A2 activity in smokers. Within the framework of a hospital-based case/control study, we investigated the relationship between CYP1A2 polymorphisms, occupational/environmental exposures and bladder cancer (BC) risk. The study population included 185 BC cases and 180 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). A case-only design was applied to study the interaction between CYP1A2 -2467T/delT (or -163C/A) and occupational and environmental factors. Multiple logistic regression showed a significantly increased risk among heavy smokers (> or =50 packyears; OR 5.6, 95% CI: 2.5-12.5) and heavy coffee drinkers (>5 cups/day; OR 3.1, 95% CI: 1.2-7.9). Exposure to AAs showed a significant trend of BC risk with increasing cumulative exposure (CE) (P = 0.04), with heavy smoking as possible confounder. A decreased risk was noted for large leaf vegetable consumption, with significant trend from <1/month to >3 times/week (P = 0.008). The case-only analysis showed an interaction between -2467T/delT and tobacco smoking >25 packyears (P = 0.04); no interaction was detected between such polymorphisms and coffee consumption, dietary habits and occupational exposure to AAs. No effects were shown with -163C/A genotype as well as no overall effect of CYP1A2 by itself on BC risk. This is the first study suggesting that CYP1A2 -2467T/delT modifies the effect of cigarette smoking on BC risk.
Pavanello
Sofia
S
Occupational Health Section, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, 35128, Padova, Italy. sofia.pavanello@unipd.it
Mastrangelo
Giuseppe
G
Placidi
Donatella
D
Campagna
Marcello
M
Pulliero
Alessandra
A
Carta
Angela
A
Arici
Cecilia
C
Porru
Stefano
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003069:Coffee / Q000009:adverse effects; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000706:statistics & numerical data; D016017:Odds Ratio; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
D003069:Coffee; D011084:Polycyclic Aromatic Hydrocarbons; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2