Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a...

Area of Science:

• Environmental Health
• Molecular Epidemiology
• Cancer Research

Background:

• DNA adducts serve as biomarkers for carcinogen exposure and early carcinogenesis.
• Peripheral blood lymphocyte (PBL) DNA adduct levels may reflect bladder tissue adduct levels.
• Investigating PBL DNA adducts' association with bladder cancer (BC) risk and modulation by genetic and environmental factors is crucial.

Purpose of the Study:

• To explore the association between PBL DNA adducts and bladder cancer risk.
• To assess the influence of genetic polymorphisms, environmental, and occupational factors on this relationship.
• To analyze complex interrelationships using structural equation modeling (SEM).

Main Methods:

• A hospital-based case/control study involving 199 BC cases and 213 non-cancer controls (Caucasian males).
• Data collection included lifetime smoking, coffee, diet, occupation (aromatic amines [AAs], polycyclic aromatic hydrocarbons [PAHs]), and PBL DNA adducts.
• Structural Equation Modeling (SEM) was employed to analyze direct and indirect effects.

Main Results:

• No association was found between PBL DNA adducts and BC risk.
• PBL DNA adducts positively correlated with occupational cumulative AA exposure (p=0.028).
• XRCC1 Arg 399 polymorphism was linked to decreased adduct levels but not BC risk. Established risk factors (smoking, coffee, AA exposure, MnSOD, MPO) were confirmed by SEM.

Conclusions:

• Occupational cumulative AA exposure is associated with DNA adducts and BC risk, reinforcing AAs' role in bladder carcinogenesis.
• PBL DNA adducts, as snapshot measurements, may not be representative of relevant exposures for predicting BC risk.
• Future research should focus on novel biomarkers and repeated adduct measurements across life stages.