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  • It is conceivable that subgroups of ALPHA Trial participants


    It is conceivable that subgroups of ALPHA Trial participants (older, obese, low fitness; Tables S2–S4) had weaker defense mechanisms at baseline (corroborated by shorter baseline LTL; Table S4) and could not counteract the detrimental, acute effects of exercise on LTL reported in the literature [52]. Strengths of our study include a partially supervised exercise intervention and a large sample size for examining exercise-only effects on LTL. Mason et al. described the second-largest trial, in 204 postmenopausal women [35]. Confounding was not a major concern in our study given our randomized design. The imbalances we observed in baseline characteristics between the exercise and control groups were subtle and unlikely to explain our primary results. Our findings are generalizable to non-smoking, physically inactive, postmenopausal women with average BMI ≈ 29 kg/m2, high socioeconomic status, and no major chronic illnesses. A possible limitation of our study was a lack of statistical power to detect intervention effects, particularly in subgroup analyses. Furthermore, we did not assess changes in psychological stress [53] or sedentary behavior [19,37,54] in our study, possibly overlooking significant effect modification. While the inter-assay CV was similar to that found in previous studies [[55], [56], [57]], it Liproxstatin-1 is was relatively high and could be a potential reason for the lack of association found in this study.
    Conclusion Results from our study, and Liproxstatin-1 all previous RCTs on this topic [[35], [36], [37]], have not demonstrated statistically significant exercise effects on telomere attrition. Future research should aim for improved precision in LTL measurement and standardization of methods to better compare between studies. While our results are inconsistent with observational studies, a causal relation cannot be ruled out given the limited scope of our RCT. If the true exercise effect on LTL depends on the presence or absence of other factors at baseline, then future long-term RCTs could be designed to address those factors specifically. Those data will be crucial in identifying who benefits from exercise with respect to telomeres and disease risks.
    Funding This work was supported by the Canadian Breast Cancer Research Alliance (#13576) and the Canadian Institutes of Health Research (#130238). Dr Friedenreich held a Health Senior Scholar Award from Alberta Innovates-Health Solutions (AI-HS) and the Alberta Cancer Foundation (ACF) Weekend to End Women’s Cancers Breast Cancer Chair. Dr Courneya was supported by the Canada Research Chairs Program. Dr Brenner was supported by a Canadian Cancer Society Research Institute Capacity Development Award in Cancer Prevention. Dr Conroy was supported by postdoctoral fellowship awards from the Canadian Institutes of Health Research and AI-HS. Dr Beattie was supported by career awards from AI-HS and ACF.
    Authorship contributions statement
    Conflicts of interest
    Introduction Coffee and tea are postulated to influence the development of cancer [[1], [2], [3]], but the underlying mechanisms remain unclear. Nevertheless, these beverages contain certain compounds, such as polyphenols and caffeine, which may prevent carcinogenesis through several mechanisms including scavenging free radicals, inhibiting inflammatory processes, minimizing DNA damage, improving insulin sensitivity, increasing levels of sex hormone binding globulin, reducing levels of free estradiol and reducing circulating glucose levels [1,[4], [5], [6], [7], [8], [9]]. Conversely, evidence from some studies has indicated that these beverages may induce carcinogenesis through processes such as tumor cell proliferation [[10], [11], [12], [13]]. Based on these observations, several epidemiological studies have been conducted to elucidate the role that coffee and tea, as well as caffeine, a component of these beverages, may play in the development of breast, endometrial, and ovarian cancers. While most studies do not support an association of coffee and caffeine intake with risk of breast cancer [[14], [15], [16], [17], [18], [19]], a few studies have shown an inverse association with total coffee intake [20,21]. There is also little support for an association between coffee or caffeine intake and risk of ovarian cancer [13,18,[22], [23], [24]]. More consistent findings have been observed for the association between coffee consumption and risk of endometrial cancer, with most studies reporting an inverse association [7,[25], [26], [27], [28], [29], [30]]. Caffeine, however, does not appear to be associated with risk of endometrial cancer, as the results of epidemiological studies, to date, have mostly been null [28,29,31,32]. Studies assessing overall tea intake have largely failed to observe associations with risk of breast, endometrial or ovarian cancer [23,29,[31], [32], [33], [34], [35]].