Body mass index and molecular subtypes of colorectal cancer
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Published version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease. METHODS: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables. RESULTS: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control). CONCLUSIONS: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.
Date Issued
2023-02
Date Acceptance
2022-10-13
Citation
Journal of the National Cancer Institute, 2023, 115 (2), pp.165-173
ISSN
0027-8874
Publisher
Oxford University Press
Start Page
165
End Page
173
Journal / Book Title
Journal of the National Cancer Institute
Volume
115
Issue
2
Copyright Statement
©The Author(s) 2022. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For
commercial re-use, please contact journals.permissions@oup.com
commercial re-use, please contact journals.permissions@oup.com
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36445035
PII: 6851145
Subjects
Humans
Female
Body Mass Index
Proto-Oncogene Proteins B-raf
Colorectal Neoplasms, Hereditary Nonpolyposis
Microsatellite Instability
Proto-Oncogene Proteins p21(ras)
Colorectal Neoplasms
Risk Factors
Obesity
CpG Islands
DNA Methylation
Mutation
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2022-11-29