Carcinogenesis Advance Access published online on March 3, 2005
Carcinogenesis, doi:10.1093/carcin/bgi063
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1 Department of Occupational and Environmental medicine, Lund University, Sweden
* To whom correspondence should be addressed. Lack of functional telomeres can cause chromosomal aberrations. This type of genetic instability may promote tumorigenesis. We have investigated the association between mean telomere length in buccal cells (assessed with quantitative real-time PCR) and bladder cancer risk in a case-control study. Patients with bladder cancer displayed significantly shorter telomeres than control subjects (p=0.001). Median telomere length ratio was 0.95 (range 0.53-3.2) for cases and 1.1 (0.51-2.4) for controls. Moreover, the adjusted odds ratio (OR) for bladder cancer was significantly increased in the quartile with the shortest telomere length OR=4.5 (95% confidence interval [CI] 1.7-12). It is known that oxidative stress, alkylation, or UV radiation increases shortening of telomeres. Thus, we also analyzed whether environmental and genetic factors associated with DNA damage, i.e., smoking, and polymorphisms in genes involved in metabolism of genotoxic carcinogens (EPHX1, GSTA1, GSTM1, GSTP1, GSTT1, NAT1, NAT2, and NQO1) or DNA repair (APE1, NBS1, XPC, XPD, XRCC1, XRCC3, and XRCC4), could modify the association between telomere length and cancer risk. A clear effect of smoking and telomere length could be observed. Current smokers with short telomeres had more than six times as high risk as non-smokers/former smokers with long telomeres (OR=6.3, 95% CI 1.7-23). Lack of the biotransformation gene GSTM1 and short telomeres were associated with OR=6.5 (95% CI 2.4-18), whereas homozygous carriers of 312Asn in the DNA repair gene XPD, with short telomeres, displayed an OR of 17 (95% CI 1.9-150). However, no significant interaction for cancer risk could be proven for telomere length, smoking, and susceptibility genotypes of metabolizing and DNA-repairing genes.
Received December 15, 2004
Revised February 22, 2005
Accepted February 22, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer
2 RSKC, Lund University Hospital, Sweden
3 Department of Clinical Genetics, Lund University, Sweden
Karin Broberg, E-mail: karin.broberg{at}ymed.lu.se
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