Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study

作者：Eleanor L. Watts, Tomas I. Gonzales, Tessa Strain, Pedro F. Saint‐Maurice, D. Timothy Bishop, Stephen J. Chanock, Mattias Johansson, Temitope O. Keku, Loic Le Marchand, Vı́ctor Moreno, Polly A. Newcomb, Christina C. Newton, Rish K. Pai, Mark P. Purdue, Cornelia M. Ulrich, Karl Smith-Byrne, Bethany Van Guelpen, Rosalind A. Eeles, Christopher A. Haiman, Zsofia Kote‐Jarai, Fredrick R. Schumacher, Sara Benlloch, Ali Amin Al Olama, Kenneth R. Muir, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen J. Chanock, Ying Wang, Catherine M. Tangen, Jyotsna Batra, Judith A. Clements, APCB BioResource (Australian Prostate Cancer BioResource), Henrik Grönberg, Nora Pashayan, Johanna Schleutker, Demetrius Albanes, Stephanie J. Weinstein, Alicja Wolk, Catharine West, Lorelei A. Mucci, Géraldine Cancel‐Tassin, Stella Koutros, Karina D. Sørensen, Eli Marie Grindedal, David E. Neal, Freddie C. Hamdy, Jenny Donovan, Ruth C. Travis, Robert J. Hamilton, Sue A. Ingles, Barry S. Rosenstein, Yong‐Jie Lu, Graham G. Giles, Robert J. MacInnis, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Sune F. Nielsen, Hermann Brenner, Christiane Maier, Jeri Kim, Esther M. John, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Jose E. Castelao, Monique J. Roobol, F. Ménégaux, Kay-Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, Stephen N. Thibodeau, David J. Hunter, Peter Kraft, William J. Blot, Elio Ríboli, Felix R. Day, Katrien Wijndaele, Nicholas J. Wareham, Charles E. Matthews, Steven C. Moore, Søren Brage · 发表于：British Journal of Cancer · 年份：2023 · DOI：10.1038/s41416-023-02489-3 · 被引用次数：8 · 研究领域：Genetic Associations and Epidemiology、Cancer Genomics and Diagnostics、BRCA gene mutations in cancer

Abstract Background The association of fitness with cancer risk is not clear. Methods We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 ( N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. Results After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O 2 ⋅min −1 ⋅kg −1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O 2 ⋅min −1 ⋅kg −1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. Discussion Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.