Telomere length, arsenic exposure and risk of basal cell carcinoma of skin

Nalini Srinivas, Sivaramakrishna Rachakonda, Thomas Hielscher, Silvia Calderazzo, Peter Rudnai, Eugen Gurzau, Kvetoslava Koppova, Tony Fletcher, Rajiv Kumar

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4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)715-723
Number of pages9
JournalCarcinogenesis
Volume40
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • Cancer Research

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    Srinivas, N., Rachakonda, S., Hielscher, T., Calderazzo, S., Rudnai, P., Gurzau, E., Koppova, K., Fletcher, T., & Kumar, R. (2019). Telomere length, arsenic exposure and risk of basal cell carcinoma of skin. Carcinogenesis, 40(6), 715-723. https://doi.org/10.1093/carcin/bgz059