Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer
Abstract
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. Therefore, we also analyzed whether environmental and genetic factors associated with DNA damage, i.e. smoking and polymorphisms in the genes involved in the 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 higher 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.
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An inverse correlation with the length of telomeres was shown for the development of cardiovascular disease, renal failure, various cancers, Alzheimer's disease, and Parkinson's disease.
“Additionally, an inverse correlation with the length of telomeres was shown for the development of cardiovascular disease [44-47], renal failure [48, 49], various cancers [50, 51], Alzheimer's disease [52], and Parkinson's disease [53].”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [50]
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- Authors
- Broberg, K., Björk, J., Paulsson, K., Höglund, M., & Albin, M.
- Affiliations
- Lund University (SE)
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-03-03
- Volume
- 26
- Issue
- 7
- Pages
- 1263-1271
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2116287388
- Cited by
- 255
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 8 · 2023: 8 · 2022: 3 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 9 · 2016: 12 · 2015: 14 · 2014: 16 · 2013: 30 · 2012: 20
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- telomere length, bladder cancer, genetic susceptibility, smoking, GSTM1, XPD, DNA repair genes, gene-environment interaction, buccal epithelial cells, DNA damage
- MeSH terms
- Adult, Aged, Aged, 80 and over, Urinary Bladder Neoplasms, Carcinogens, DNA Damage, DNA Repair, Female, Genetic Markers, Genotype, Glutathione Transferase, Humans, Male, Middle Aged, Risk Factors, Smoking, Odds Ratio, Case-Control Studies, Polymerase Chain Reaction, Telomere, Genetic Predisposition to Disease
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