UNASSIGNED: Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various @entity5 . These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common @entity5 types (breast, lung, @entity43 , including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and @entity5 risk. The long TL genetic score was significantly associated with increased risk of @entity2220 (P = 6.3 * 10(-15)), even after exclusion of a SNP residing in a known @entity2 susceptibility region ( @entity2215 - @entity2217 ) P = 6.6 * 10(-6)). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for @entity2220 corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other @entity5 types or subtypes. Our finding that genetic determinants of long TL increase @entity2220 risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL @entity2220 risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in @entity2220 risk.

Genetic determinants of telomere length and risk of common XXXX : a Mendelian randomization study.

@entity43 :: ('MESH:D010051', 'Disease') :: ['colorectal, ovarian and prostate cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'cancer'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity2217 :: ('81037', 'Gene') :: ['CLPTM1L'] @entity2215 :: ('7015', 'Gene') :: ['TERT'] @entity2220 :: ('MESH:C538231', 'Disease') :: ['lung adenocarcinoma', 'increases lung adenocarcinoma']
@entity5 :: (MESH:D009369,Disease) :: ['cancers']
