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Telomere length, arsenic exposure and risk of basal cell carcinoma of skin.
Srinivas, Nalini; Rachakonda, Sivaramakrishna; Hielscher, Thomas; Calderazzo, Silvia; Rudnai, Peter; Gurzau, Eugen; Koppova, Kvetoslava; Fletcher, Tony; Kumar, Rajiv.
Afiliación
  • Srinivas N; Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
  • Rachakonda S; Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
  • Hielscher T; Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
  • Calderazzo S; Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
  • Rudnai P; Department of Environmental Epidemiology, National Public Health Center, Budapest, Hungary.
  • Gurzau E; Health Department, Environmental Health Center, Babes Bolyai University, Cluj, Romania.
  • Koppova K; Department of Environmental Health, Slovak Medical University Bratislava, Banska Bystrica, Slovakia.
  • Fletcher T; London School of Hygiene and Tropical Medicine, London, UK.
  • Kumar R; Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Carcinogenesis ; 40(6): 715-723, 2019 07 06.
Article en En | MEDLINE | ID: mdl-30874287
ABSTRACT
Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study, based on arsenic-exposed 528 cases with basal cell carcinoma (BCC) of skin and 533 healthy controls, we investigated effect of telomere length, measured by real-time PCR, on the disease risk. We observed a statistically significant association between decreased telomere length and increased BCC risk [odds ratio (OR) = 5.92, 95% confidence interval (CI) = 3.92 to 9.01, P < 0.0001]. Due to confounder effect of arsenic exposure, in a two-sample Mendelian randomization (MR), telomere length associated single-nucleotide polymorphisms as instrument variables violated valid assumptions; however, one-sample MR adjusted for arsenic exposure indicated an increased risk of BCC with short telomeres. The interaction between arsenic exposure and telomere length on BCC risk was statistically significant (P = 0.02). Within each tertile based on arsenic exposure, the individuals with shorter telomeres were at an increased risk of BCC, with highest risk being in the highest exposed group (OR = 16.13, 95% CI = 6.71 to 40.00, P < 0.0001), followed by those in medium exposure group and low exposure group. The combined effect of highest arsenic exposure and shortest telomeres on BCC risk (OR = 10.56, 95% CI = 5.14 to 21.70) showed a statistically significant departure from additivity (interaction contrast ratio 6.56, P = 0.03). Our results show that in the presence of arsenic exposure, decreased telomere length predisposes individuals to increased risk of BCC, with the effect being synergistic in individuals with highest arsenic exposure and shortest telomeres.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 Problema de salud: 2_quimicos_contaminacion Asunto principal: Arsénico / Neoplasias Cutáneas / Carcinoma Basocelular / Telómero / Predisposición Genética a la Enfermedad / Exposición a Riesgos Ambientales Tipo de estudio: Clinical_trials / Etiology_studies / Observational_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Carcinogenesis Año: 2019 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 Problema de salud: 2_quimicos_contaminacion Asunto principal: Arsénico / Neoplasias Cutáneas / Carcinoma Basocelular / Telómero / Predisposición Genética a la Enfermedad / Exposición a Riesgos Ambientales Tipo de estudio: Clinical_trials / Etiology_studies / Observational_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Carcinogenesis Año: 2019 Tipo del documento: Article País de afiliación: Alemania
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