Title
Polymorphisms in genes related to activation or detoxification of carcinogens might interact with smoking to increase renal cancer risk: Results from The Netherlands Cohort Study on diet and cancer
Author
Smits, K.M.
Schouten, L.J.
van Dijk, B.A.C.
van Houwelingen, K.
van de Hulsbergen-Kaa, C.A.
Kiemeney, L.A.L.M.
van Houwelingen, K.
Goldbohm, R.A.
Oosterwijk, E.
van den Brandt, P.A.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
Metabolic gene polymorphisms have previously been suggested as risk factors for renal cell carcinoma (RCC). These polymorphisms are involved in activation or detoxification of carcinogens in cigarette smoke which is another RCC risk factor. We evaluated gene-environment interactions between CYP1A1, GSTμ1 and smoking in a large population-based RCC case group. The Netherlands Cohort Study on diet and cancer (NLCS) comprises 120,852 persons who completed a questionnaire on smoking and other risk factors at baseline. After 11.3 years of follow-up, 337 incident RCC cases were identified. DNA was collected for 245 cases. In a case-only analysis, interaction-odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression. We observed a moderate, not statistically significant, interaction between current smoking and CYP1A1*2C (OR 1.42; 95% CI 0.70-2.89) and GSTμ1 null (OR 1.35; 95% CI 0.65-2.79). For current smokers with both a variant (heterozygous or homozygous) in CYP1A1 and GSTμ1 null, risk was also increased (OR 1.63; 95% CI 0.63-4.24). No interaction was observed between ever smokers, smoking duration (increments of 10 smoking years) or amount (increments of 5 cigarettes/day) and CYP1A or GSTμ1. Our results show a modest trend towards a statistically significant gene-environment interaction between CYP1A1, GSTμ1 and smoking in RCC. This could indicate that RCC risk among smokers might be more increased with the CYP1A1*2C genotype, GSTμ1 null, or both a CYP1A1 variant and GSTμ1 null. © Springer-Verlag 2007.
Subject
Healthy for Life
Health
Healthy Living
Leefomgeving en gezondheid
CYP1A1 genotype
Gene-environment interaction
GSTμ1 genotype
Renal cell cancer
Smoking
carcinogen
cytochrome P450 1A1
DNA
glutathione S-transferase M1
glutathione transferase
glutathione transferase M1
agar gel electrophoresis
aged
article
biotransformation
comparative study
female
follow up
genetic polymorphism
genetics
genotype
human
incidence
kidney carcinoma
kidney tumor
male
middle aged
Netherlands
polymerase chain reaction
prospective study
risk factor
smoking
Aged
Biotransformation
Carcinogens
Carcinoma, Renal Cell
Cytochrome P-450 CYP1A1
DNA, Neoplasm
Electrophoresis, Agar Gel
Female
Follow-Up Studies
Genotype
Glutathione Transferase
Humans
Incidence
Kidney Neoplasms
Male
Middle Aged
Netherlands
Polymerase Chain Reaction
Polymorphism, Genetic
Prospective Studies
Risk Factors
Smoking
To reference this document use:
http://resolver.tudelft.nl/uuid:8709ad4d-ed24-48a0-babc-bff36546fa7b
DOI
https://doi.org/10.1007/s00345-007-0220-5
TNO identifier
240647
ISSN
0724-4983
Source
World Journal of Urology, 26 (1), 103-110
Document type
article