Physical activity and the risk of colorectal cancer in Lynch syndrome

Abstract

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk in people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n = 807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49 and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-hr/week) during the age-period of cancer diagnosis or censoring (near-term exposure) and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. <3.5 MET-hr/week, 0.71; 95% CI, 0.53-0.96). The strength and direction of associations were similar for long-term physical activity, although the associations were not nominally significant. Our results suggest that physical activity is inversely associated with the risk of colorectal cancer for people with Lynch syndrome; however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk in people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk.

Body Weight, Physical Activity, and Risk of Cancer in Lynch Syndrome

“…Our results suggest that performing more vigorous guided physical activity exhibit a cancer-preventive effect in men, as those who continued at higher levels of physical activity were at a 63% lower cancer risk when compared to less active men performing non-guided physical activity. To date, we are aware of only two previous studies that have assessed the impact of physical activity on LS cancer risk [ 13 , 14 ]. Both designs were retrospective like our study but did not assess risk estimates separately for men and women.…”

“…There is strong evidence derived from the general population that increased physical activity and reduced body adiposity are associated with decreased cancer risk [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Recent research suggests that LS CRC risk can also be moderated by these lifestyle factors [ 13 , 14 , 15 , 16 , 17 ], but the number of studies that investigate the associations between lifestyle and LS cancer risk are scarce. Currently, there are only two studies that we are aware of that have assessed the association of physical activity and LS cancer risk [ 13 , 14 ] and they have not taken into consideration the fact that this potential association may vary during a lifespan.…”

“…Recent research suggests that LS CRC risk can also be moderated by these lifestyle factors [ 13 , 14 , 15 , 16 , 17 ], but the number of studies that investigate the associations between lifestyle and LS cancer risk are scarce. Currently, there are only two studies that we are aware of that have assessed the association of physical activity and LS cancer risk [ 13 , 14 ] and they have not taken into consideration the fact that this potential association may vary during a lifespan. In addition, the evidence regarding the associations of cancer risk and obesity and overweight is contradictory among women with LS [ 15 ], and thus, the risk analyses should be performed separately for both sexes.…”

Type 2 diabetes mellitus, blood cholesterol, triglyceride and colorectal cancer risk in Lynch syndrome

“…To minimise bias caused by this non-random ascertainment, we used a "weighted cohort approach" described by Antoniou et al, 20 which has been used in similar studies of modifiers for Lynch syndrome. [21][22][23][24][25][26] Briefly, we first calculated the incidence rates of colorectal cancer for the MMR mutation carriers for age groups <30, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64 and >64 based on colorectal cancer incidence in the general population, averaged for men and women, 27 and the hazard ratio of colorectal cancer for each MMR gene mutated. 9,10,28 These incidence rates was then used together with the number and total person-years of observation for affected and unaffected carriers in each age group to calculate the age-specific sampling fractions.…”

Rising rates of colorectal cancer in younger adults

“…Hereditary syndromes are more common in people with young onset colorectal cancer. However, although this group has increased susceptibility to environmental factors,1617 they can explain, at most, only a small proportion of the change.…”