Carcinogenesis Advance Access originally published online on February 19, 2004
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Carcinogenesis, Vol. 25, No. 6, 923-929,
June 2004
Carcinogenesis vol.25 no.6 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Low CYP1A2 activity associated with testicular cancer
1 Department of Pharmacology, The Panum Institute, University of Copenhagen, 2 Danish Cancer Society, Division for Cancer Epidemiology, Copenhagen, 3 Department of Oncology, Herlev University Hospital, Copenhagen, 4 Department of Internal Medicine, Roskilde County Hospital, Roskilde, 5 Department of Oncology, Rigshospitalet, Copenhagen, 6 Department of Clinical Pharmacology Q, Rigshospitalet, Copenhagen, 7 Institute of Public Health, University of Copenhagen and 8 Department of Medicine P, Bispebjerg Hospital, Copenhagen, Denmark
9 To whom correspondence should be addressed Email: hepo{at}rh.dk
The incidence rate of testicular cancer has increased during the last 50 years. An interplay between changing environmental factors and individual susceptibility, e.g. in foreign compound metabolizing enzymes, may have important influences on the risk of testicular cancer. The cytochrome P4501A2 (CYP1A2) enzyme and the bimodally expressed enzyme N-acetyltransferase2 (NAT2) metabolize many procarcinogens/carcinogens. The aim of this population-based case-control study was to investigate if CYP1A2 or NAT2 activity measured as a ratio of urinary metabolites of dietary caffeine is a risk factor in testicular cancer. 378 men participated (80 seminomas, 104 non-seminomas and 194 controls). The CYP1A2 activity was lower in the cases than in the controls [median and 30–70% percentiles: 4.7 (3.9–5.7) and 5.2 (4.4–6.4), respectively]. The subjects were classified in tertiles with low, medium or high CYP1A2 activity. A low CYP1A2 activity was associated with the highest risk of testicular cancer. Including all participants except men using drugs suspected to influence CYP1A2 activity (n = 15), medium and low activity conferred odds ratios (ORs) of 1.54 [confidence intervals of 95% (CI95%) 0.93–2.55] and 2.11; CI95% (1.23–3.62), respectively, of having testicular cancer. Excluding smokers (n = 157) the ORs of medium and low activity were 3.63; CI95% (1.53–8.60) and 4.70; CI95% (2.03–10.89), respectively. After further exclusion of cases that had received chemotherapy or radiation (n = 47), similar significant results were achieved. In the groups with the lowest CYP1A2 activity the ORs for seminoma and non-seminoma were 2.12; CI95% (0.93–4.81) and 2.10; CI95% (1.02–4.32). The phenotype of NAT2 was not associated with testicular cancer. In conclusion, we found no association of NAT2 phenotype to testicular cancer, whereas significant associations between CYP1A2 activity and testicular cancer were shown.
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