Year: 2015
Type: dissertation
Abstract: A strong body of observational evidence supports the notion that physical activity \n(PA) is inversely associated with colon cancer (CC) risk. Epigenetic alterations, such \nas aberrant DNA methylation, are apparent in the early stages of carcinogenesis. \nRecent evidence has suggested that PA can alter DNA methylation patterns in a \nvariety of tissues. It is not known whether PA can affect DNA methylation patterns in \ngenes implicated in CC risk. Study 1 was a longitudinal investigation of 253 females \n(70.7 ± 4.0 yrs) and 137 males (71.4 ± 4.3 yrs) for whom DNA from peripheral blood \nleukocytes were available. Participants showed differential DNA methylation of \nrelevant genes depending on whether they had increased, decreased, or maintained \ntheir PA level over eight years. Study 2 was a randomised controlled trial of sedentary \ncolon adenoma patients (n = 31; 68.5 ± 3.2 yrs) who were randomised to a 6-12 \nmonth Active Lifestyle Programme or Usual Care. DNA methylation patterns of CC \nrisk genes in buccal cells were unaffected by taking part in the Active Lifestyle \nProgramme. Low recruitment probably resulted in the study being underpowered, and \nbuccal cells may not have been a suitable surrogate marker of colon DNA \nmethylation. A lack of colon biopsies prevented any analysis of changes in \nmethylation in this tissue. Due to the absence of colon biopsies, Study 3 tested \nwhether serum from physically active or inactive volunteers affected the proliferation \nof in vitro models of colon epithelia, in the fasted state and after a single bout of \ntreadmill running. A randomised controlled trial with a crossover design was \nconducted in 20 male participants (59 ± 6.0 yrs) free of metabolic or cardiovascular \ndisease, and data pooled together with 20 male colon adenoma patients from the \nprevious investigation. This study showed that male adenoma patients’ \ncardiorespiratory fitness was inversely correlated with serum-stimulated growth of the \ncolorectal cancer cell line Caco-2 in vitro, but no relationship was observed in \ndisease-free volunteers at rest or after exercise. In conclusion, this series of studies \ndemonstrated that whilst PA is associated with beneficial changes in DNA methylation \nlongitudinally, this might not be realised in a trial setting with sedentary older persons. \nIt remains unclear whether increasing PA is an effective strategy for reducing CC risk \nvia changes to DNA methylation patterns. Furthermore, it has suggested that \ncardiorespiratory fitness might be important in modulating the growth of the Caco-2 \ncell line, but more investigation is needed.
Author: Barnabas Shaw
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2582881260