%0 Journal Article
%A Morales Berstein, Fernanda
%A McCartney, Daniel L
%A Lu, Ake T
%A Tsilidis, Konstantinos K
%A Bouras, Emmanouil
%A Haycock, Philip
%A Burrows, Kimberley
%A Phipps, Amanda I
%A Buchanan, Daniel D
%A Cheng, Iona
%A Martin, Richard M
%A Davey Smith, George
%A Relton, Caroline L
%A Horvath, Steve
%A Marioni, Riccardo E
%A Richardson, Tom G
%A Richmond, Rebecca C
%A Eeles, Rosalind A
%A Haiman, Christopher A
%A Kote-Jarai, Zsofia
%A Schumacher, Fredrick R
%A Benlloch, Sara
%A Al Olama, Ali Amin
%A Muir, Kenneth R
%A Berndt, Sonja I
%A Conti, David V
%A Wiklund, Fredrik
%A Chanock, Stephen
%A Wang, Ying
%A Tangen, Catherine M
%A Batra, Jyotsna
%A Clements, Judith A
%A Apcb BioResource Australian Prostate Cancer BioResource
%A Grönberg, Henrik
%A Pashayan, Nora
%A Schleutker, Johanna
%A Albanes, Demetrius
%A Weinstein, Stephanie
%A Wolk, Alicja
%A West, Catharine M L
%A Mucci, Lorelei A
%A Cancel-Tassin, Géraldine
%A Koutros, Stella
%A Sørensen, Karina Dalsgaard
%A Grindedal, Eli Marie
%A Neal, David E
%A Hamdy, Freddie C
%A Donovan, Jenny L
%A Travis, Ruth C
%A Hamilton, Robert J
%A Ingles, Sue Ann
%A Rosenstein, Barry S
%A Lu, Yong-Jie
%A Giles, Graham G
%A MacInnis, Robert J
%A Kibel, Adam S
%A Vega, Ana
%A Kogevinas, Manolis
%A Penney, Kathryn L
%A Park, Jong Y
%A Stanford, Janet L
%A Cybulski, Cezary
%A Nordestgaard, Børge G
%A Nielsen, Sune F
%A Brenner, Hermann
%A Maier, Christiane
%A Kim, UJeri
%A John, Esther M
%A Teixeira, Manuel R
%A Neuhausen, Susan L
%A De Ruyck, Kim
%A Razack, Azad
%A Newcomb, Lisa F
%A Lessel, Davor
%A Kaneva, Radka
%A Usmani, Nawaid
%A Claessens, Frank
%A Townsend, Paul A
%A Esteban Castelao, Jose
%A Roobol, Monique J
%A Menegaux, Florence
%A Khaw, Kay-Tee
%A Cannon-Albright, ULisa
%A Pandha, Hardev
%A Thibodeau, Stephen N
%A Hunter, David J
%A Kraft, Peter
%A Blot, William J
%A Riboli, Elio
%T Assessing the causal role of epigenetic clocks in the development of multiple cancers: a Mendelian randomization study.
%J eLife
%V 11
%@ 2050-084X
%C Cambridge
%I eLife Sciences Publications
%M DKFZ-2022-00897
%P e75374
%D 2022
%X Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker.We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach.Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95
%K Colorectal Neoplasms: epidemiology
%K Colorectal Neoplasms: genetics
%K Epigenesis, Genetic
%K Genome-Wide Association Study: methods
%K Humans
%K Male
%K Mendelian Randomization Analysis
%K Polymorphism, Single Nucleotide
%K DNA methylation (Other)
%K Mendelian randomization (Other)
%K cancer (Other)
%K epidemiology (Other)
%K epigenetic age acceleration (Other)
%K epigenetic clocks (Other)
%K genetics (Other)
%K genomics (Other)
%K human (Other)
%K medicine (Other)
%9 Journal Article
%$ pmid:35346416
%2 pmc:PMC9049976
%R 10.7554/eLife.75374
%U https://inrepo02.dkfz.de/record/179790