Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study

TY - JOUR

T1 - Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer

T2 - A Prospective Investigation in the CAPP2 Study

AU - Movahedi, Mohammad

AU - Bishop, D Timothy

AU - Macrae, Finlay

AU - Mecklin, Jukka-Pekka

AU - Moeslein, Gabriela

AU - Olschwang, Sylviane

AU - Eccles, Diana

AU - Evans, D Gareth

AU - Maher, Eamonn R

AU - Bertario, Lucio

AU - Bisgaard, Marie-Luise

AU - Dunlop, Malcolm G

AU - Ho, Judy W C

AU - Hodgson, Shirley V

AU - Lindblom, Annika

AU - Lubinski, Jan

AU - Morrison, Patrick J

AU - Murday, Victoria

AU - Ramesar, Raj S

AU - Side, Lucy

AU - Scott, Rodney J

AU - Thomas, Huw J W

AU - Vasen, Hans F

AU - Burn, John

AU - Mathers, John C

N1 - © 2015 by American Society of Clinical Oncology.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Purpose: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). Patients and Methods: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2×2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. Results: During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41 X (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2 increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). Conclusion: Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.

AB - Purpose: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). Patients and Methods: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2×2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. Results: During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41 X (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2 increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). Conclusion: Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.

KW - Adaptor Proteins, Signal Transducing

KW - Adiposity

KW - Adult

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Aspirin

KW - Body Mass Index

KW - Body Weight

KW - Colorectal Neoplasms

KW - Colorectal Neoplasms, Hereditary Nonpolyposis

KW - DNA-Binding Proteins

KW - Female

KW - Follow-Up Studies

KW - Heterozygote

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - MutS Homolog 2 Protein

KW - Mutation

KW - Nuclear Proteins

KW - Obesity

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1200/JCO.2014.58.9952

DO - 10.1200/JCO.2014.58.9952

M3 - Journal article

C2 - 26282643

SN - 0732-183X

VL - 33

SP - 3591

EP - 3597

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 31

ER -