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

• Published in: Carcinogenesis (New York) Vol. 40; no. 6; pp. 715 - 723
• Main Authors: Srinivas, Nalini, Rachakonda, Sivaramakrishna, Hielscher, Thomas, Calderazzo, Silvia, Rudnai, Peter, Gurzau, Eugen, Koppova, Kvetoslava, Fletcher, Tony, Kumar, Rajiv
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 06.07.2019
• Subjects: Aged; Arsenic - toxicity; Carcinoma, Basal Cell - chemically induced; Carcinoma, Basal Cell - genetics; Case-Control Studies; Environmental Exposure; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Skin Neoplasms - chemically induced; Skin Neoplasms - genetics; Telomere - drug effects
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgz059

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. In a series of 528 skin BCC patients and 533 matching controls, we describe an association between telomere length and risk modulation by arsenic exposure. We show a synergistic interaction between arsenic exposure and telomere length on the BCC risk.