Relationship between Telomere Length, Genetic Traits and Environmental/Occupational Exposures in Bladder Cancer Risk by Structural Equation Modelling

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).

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.

International journal of environmental research and public health. 2017 Dec 21*** epublish ***

Sofia Pavanello, Angela Carta, Giuseppe Mastrangelo, Manuela Campisi, Cecilia Arici, Stefano Porru

Department of Cardiac, Thoracic and Vascular Sciences, Unit of Occupational Medicine, University of Padova, 35128 Padova, Italy. ., Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, 25123 Brescia, Italy. ., Department of Cardiac, Thoracic and Vascular Sciences, Unit of Occupational Medicine, University of Padova, 35128 Padova, Italy. ., Department of Cardiac, Thoracic and Vascular Sciences, Unit of Occupational Medicine, University of Padova, 35128 Padova, Italy. ., Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, 25123 Brescia, Italy. ., University Research Center "Integrated Models for Prevention and Protection in Environmental and Occupational Health" (MISTRAL), University of Brescia, 25123 Brescia, Italy. .