Physical activity and the risk of colorectal cancer in Lynch syndrome.

Dashti SG1, Win AK1,2, Hardikar SS3,4, Glombicki SE5, Mallenahalli S5, Thirumurthi S5, Peterson SK6, You YN7, Buchanan DD1,2,8,9, Figueiredo JC10,11, Campbell PT12, Gallinger S13, Newcomb PA3,14, Potter JD3, Lindor NM15, Le Marchand L16, Haile RW17, Hopper JL1, Jenkins MA1, Basen-Engquist KM6, Lynch PM5, Pande M5.

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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 for 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-h/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-h/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 for people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. This article is protected by copyright. All rights reserved.