Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling.
DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC) risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM) analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 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). No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028), whereas XRCC1 Arg 399 (p<0.006) was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001), coffee (p<0.001), cumulative AAs exposure (p = 0.041) and MnSOD (p = 0.009) and a decreased risk by MPO (p<0.008) were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different critical life stages.
Department of Medical-Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, Brescia, Italy.
Stefano
S
Porru
Department of Cardiac, Thoracic, and Vascular Sciences, Unit of Occupational Medicine, University of Padova, Padova, Italy.
Sofia
S
Pavanello
Department of Medical-Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, Brescia, Italy.
Angela
A
Carta
Department of Medical-Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, Brescia, Italy.
Cecilia
C
Arici
Department of Medical-Surgical Specialties, Radiological Sciences and Public Health, Section of Surgical Specialties, University of Brescia, Brescia, Italy.
Claudio
C
Simeone
Department of Health Sciences, University of Genoa, Italy/Mutagenesis Unit, IRCCS Hospital-University San Martino Company - IST National Institute for Cancer Research, Genoa, Italy.
Alberto
A
Izzotti
Department of Cardiac, Thoracic, and Vascular Sciences, Unit of Occupational Medicine, University of Padova, Padova, Italy.
Giuseppe
G
Mastrangelo
D000328:Adult; D000368:Aged; D001596:Benzylamines / Q000009:adverse effects; D016022:Case-Control Studies; D003069:Coffee / Q000009:adverse effects; D018736:DNA Adducts / Q000032:analysis* / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D059647:Gene-Environment Interaction; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016273:Occupational Exposure / Q000009:adverse effects; D009195:Peroxidase / Q000235:genetics; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D000076105:X-ray Repair Cross Complementing Protein 1
D001596:Benzylamines; D003069:Coffee; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D009195:Peroxidase; D013482:Superoxide Dismutase