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Strength for Health

ABSTRACT: Despite a robust literature on the benefits of exercise for cancer survivors, most of the research to date falls in two primary areas - aerobic exercise and breast cancer survivors. The focus on aerobic training alone is a concern as resistance training is critical for building the muscle mass necessary to maintain physical function. However, concerns have been raised about the potential for higher than tolerated adverse event rates during resistance training, particularly that which is unsupervised, despite a history of safe use of resistance training in other chronically diseased patient populations. The aim of this pilot study is to demonstrate the feasibility, safety and quality of life benefit of a home-based resistance-training program among colorectal cancer survivors. The investigators will recruit n=30 men and women with stage I-III colon cancer. Participants will be randomized to a home-based exercise intervention that combines aerobic and resistance exercise. Control arm participants will receive a home-based meditation program.

DISEASE(S): Colon Cancer,Colonic Neoplasms

PROVIDER: 2147054 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Many cancer survivors suffer from impairments in skeletal muscle (SkM), both in terms of reduced mass and function. Interestingly, human SkM possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in SkM following cancer survival and/or exercise training have not yet been studied. We therefore investigated genome-wide DNA methylation (the methylome) in SkM following a 5-month, 3/week treadmill-based aerobic training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. SkM biopsies were obtained before (pre) and after (post) the 5-month training period and DNA methylation was analysed using InfiniumEPIC 850K Arrays. The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e., hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre-training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at more random non-regulatory regions across the DNA compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e., hypomethylation) in 99% of the DMPs located specifically in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back towards a hypomethylated signature that was observed pre-training in healthy age-matched controls at 300 (out of 881) of these island and promoter associated CpG sites. Pathway enrichment analysis identified that the training in cancer survivors evoked this predominantly hypomethylated signature in pathways associated with: Cell cycle, DNA replication and repair, transcription, translation, mTOR signalling and proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104 and SPG7 as hypermethylated in breast cancer survivors with training reversing these CpG island / promoter associated DMRs towards a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline as well as after training in both the cancer survivors and healthy controls. In conclusion, human SkM muscle retains a hypermethylated signature for as long as 10-14 years after breast cancer treatment and survival. Importantly, 5 months of aerobic training rejuvenated the SkM methylome towards signatures identified in healthy age-matched individuals in gene regulatory regions.

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Strength for Health

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