Abstract
Background: Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods: Within the framework of a hospital-based case (n = 96)/control (n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results: The SEM analysis indicates negative direct links (p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk (p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects (p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link). Conclusions: Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention.
Highlights
Dysfunction in telomere maintenance plays an important role in human carcinogenesis; the complex relationship between telomere protection and the risk of developing bladder cancer (BC) has not been thoroughly studied
aromatic amines (AAs) (p = 0.003) and coffee (p = 0.006), while it decreased with leucocyte TL (LTL) (p = 001) and age (p = 0.019)
In this paper we report direct negative links between LTL with age, DNA adducts, alcohol and N-Acetyl Transferase 2 (NAT2), and positive ones with coffee, MPO and XRCC3; and between BC risk with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age
Summary
Dysfunction in telomere maintenance plays an important role in human carcinogenesis; the complex relationship between telomere protection and the risk of developing bladder cancer (BC) has not been thoroughly studied. Methods: Within the framework of a hospital-based case (n = 96)/control (n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Results: The SEM analysis indicates negative direct links (p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk (p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention
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