Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies Journal Article


Authors: Wang, X.; O'Connell, K.; Jeon, J.; Song, M.; Hunter, D.; Hoffmeister, M.; Lin, Y.; Berndt, S.; Brenner, H.; Chan, A. T.; Chang-Claude, J.; Gong, J.; Gunter, M. J.; Harrison, T. A.; Hayes, R. B.; Joshi, A.; Newcomb, P.; Schoen, R.; Slattery, M. L.; Vargas, A.; Potter, J. D.; Le Marchand, L.; Giovannucci, E.; White, E.; Hsu, L.; Peters, U.; Du, M.
Article Title: Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies
Abstract: Objective a € Environmental' factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear. Design Using 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height. Results Higher E-score was associated with increased CRC risk (OR quartile, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk. Conclusions Changes in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords: adult; controlled study; middle aged; major clinical study; single nucleotide polymorphism; case control study; cancer risk; cancer incidence; colorectal cancer; cancer susceptibility; cancer prevention; cohort analysis; cancer screening; smoking; body mass; population research; acetylsalicylic acid; nonsteroid antiinflammatory agent; family history; population risk; body height; fruit; vegetable; folic acid; physical activity; epidemiology; lifestyle modification; alcohol consumption; genetic predisposition; drug use; calcium intake; energy consumption; red meat; processed meat; dietary fiber; human; male; female; priority journal; article; genetic risk score
Journal Title: BMJ Open Gastroenterology
Volume: 6
ISSN: 2054-4774
Publisher: BMJ Publishing Group Ltd.  
Date Published: 2019-01-01
Start Page: e000339
Language: English
DOI: 10.1136/bmjgast-2019-000339
PROVIDER: scopus
PMCID: PMC6904202
PUBMED: 31875139
DOI/URL:
Notes: Source: Scopus
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  1. Mengmeng   Du
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