Abstract 3871: Telomere length and cancer mortality and all-cause mortality

Abstract

Abstract Introduction: Short telomeres are associated with increased age and age-related diseases. We tested the hypothesis that short telomeres are associated with increased cancer mortality and all-cause mortality. Methods: We studied 64637 individuals recruited from 1991 and onwards from two prospective cohort studies; the Copenhagen City Heart Study and the Copenhagen General Population Study. All had telomere length measured by Q-PCR in DNA from peripheral blood and had the telomere length-associated genotypes of rs1317082 (TERC), rs7726159 (TERT), and rs2487999 (OBFC1) determined. We calculated the sum of telomere length shortening alleles from the three SNPs combined. We conducted Cox regression, and instrumental variable analyses in a mendelian randomization design, using the allele sum as a genetic instrument for telomere length. Results: Telomere length shortened by 17 (P<10E-300) and 69 (P = 110E-104) base pairs per increase of one year of age, and one allele increase of allele sum, respectively. Of the 7607 deaths during up to 22 years of follow-up, 2420 were due to cancer. Shortening of telomeres (200 base pairs) was associated with increasing cancer mortality and all-cause mortality with hazard ratios of 1.02(95% CI;1.01-1.03) and 1.02(95% CI;1.02-1.03) in multifactorially adjusted models. In contrast, in the genetic analyses, the corresponding odds ratios were 0.86(95% CI;0.76-0.96) and 0.98(95% CI;0.91-1.05). Conclusion: In an observational design, short telomeres were associated with increased cancer mortality and all-cause mortality. In contrast and importantly; in a mendelian randomization design, short telomeres were associated with decreased cancer mortality, suggesting that short telomeres are likely causative in protecting against cancer mortality. Citation Format: Stig E. Bojesen, Børge G. Nordestgaard, Line Rode. Telomere length and cancer mortality and all-cause mortality. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3871. doi:10.1158/1538-7445.AM2015-3871