PT  - JOURNAL ARTICLE
AU  - Nalini Srinivas
AU  - Sivaramakrishna Rachakonda
AU  - Thomas Hielscher
AU  - Silvia Calderazzo
AU  - Peter Rudnai
AU  - Eugene Gurzau
AU  - Kvetoslava Koppova
AU  - Tony Fletcher
AU  - Rajiv Kumar
TI  - Telomere length, arsenic exposure and risk of basal cell carcinoma of skin
AID  - 10.1101/465732
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 465732
4099  - http://biorxiv.org/content/early/2018/11/08/465732.short
4100  - http://biorxiv.org/content/early/2018/11/08/465732.full
AB  - Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study, 528 cases with basal cell carcinoma of skin (BCC) and 533 healthy controls, we observed that decreased telomere length was associated with statistically significantly increased risk (OR 5.92, 95% CI 3.92-9.01, P<0.0001). We also observed that the higher arsenic exposure (>1.32 µg/L) was statistically significantly associated with decreased telomere length (β: −0.026, 95% CI: −0.05 to −0.003, P 0.02). The interaction between arsenic exposure and telomere length was statistically significant (P 0.02). Within each quantile of 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 6.71-40.00, P<0.0001); followed by those in medium exposure group (OR 5.05, 95% CI 2.29-10.20, P <0.0001), and low exposure group (OR 3.44, 95% CI 1.81-6.54, P 0.0002). The combined effect of highest arsenic exposure and shortest telomeres on the risk of BCC (OR 10.56, 95% CI 5.14 to 21.70) showed statistically significant departure from additivity (interaction constant ratio 6.56, P 0.03). Our results show that in presence of the arsenic exposure, it is the decreased telomere length that predisposes individuals to increased risk of BCC with effect being synergistic in individuals with highest arsenic exposure and shortest telomeres.