Citations 2
Body mass index and molecular subtypes of colorectal cancer
Murphy, Neil , Newton, Christina C. , Papadimitriou, Nikos , Hoffmeister, Michael , Phipps, Amanda I. , Harrison, Tabitha A. , Aglago, Elom K. , Berndt, Sonja I. , Brenner, Hermann , Cao, Yin , Chang‐Claude, Jenny , French, Amy J. , Gallinger, Steven , Georgeson, Peter , Giannakis, Marios , Gruber, Stephen B. , Harlid, Sophia , Huang, Wen‐Yi , Laskar, Ruhina Shirin , Mandic, Marko , Nowak, Johnathan A., Obón‐Santacana, Mireia , Steinfelder, Robert S. , Thibodeau, Stephen N. , Trinh, Quang M. , Tsilidis, Kostas K, Guelpen, Bethany Van , Wang, Xiaoliang , Woods, Michael O. , Zaidi, Syed Hassan Ejaz , Gunter, Marc J. , Peters, Ulrike , Song, Mingyang , Song, Mingyang , Hoffmeister, Michael , Harrison, Tabitha A , Brenner, Hermann , Cao, Yin , Chen, Xuechen , Drew, David A , Harlid, Sophia , Huang, Wen-Yi , Marchand, Loïc Le , Limburg, Paul, Sun, Wei , Ugai, Tomotaka , Van Guelpen, Bethany , Wang, Xiaoliang , Woods, Michael O , Gunter, Marc J , Murphy, Neil , Song, Mingyang , Aglago, Elom K , Obón-Santacana, Mireia , Papadimitriou, Nikos , Mandic, Marko , Trinh, Quang M , Georgeson, Peter , Newcomb, Polly A. , Buchanan, Daniel D. , Chan, Andrew T. , Cheng, Iona C. , Dimou, Niki , Drew, David A. , Farris, Alton B. , Giles, Graham G. , Hsu, Li , Jenkins, Mark A. , Marchand, Loı̈c Le , Limburg, Paul J. , Lin, Yi , Ogino, Shuji , Qu, Conghui , Sakoda, Lori C. , Schoen, Robert E. , Southey, Melissa C. , Stadler, Zsofia , Sun, Wei , Toland, Amanda Ewart , Tsilidis, Kostas K, Campbell, Peter T.
JNCI: Journal of the National Cancer Institute | November 26, 2022 | Volume: 115 | Issue: 2 | Pages: 165-173
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.
Risk Stratification for Early-Onset Colorectal Cancer Using a Combination of Genetic and Environmental Risk Scores: An International Multi-Center Study
Archambault, Alexi , Jeon, Jihyoun , Thomas, Minta , Harrison, Tabitha A. , Bishop, D. Timothy , Brenner, Hermann , Casey, Graham , Chan, Andrew T. , Chang‐Claude, Jenny , Figueiredo, Jane C. , Gallinger, Steven , Gruber, Stephen B. , Gunter, Marc J. , Hoffmeister, Michael , Li, Li , Pai, Rish K. , Parfrey, Patrick S. , Rennert, Gad , Lee, Jeffrey K. , Slattery, Martha L. , Win, Aung Ko , Woods, Michael O. , Peterse, Elisabeth F.P. , Cao, Yin , Du, Mengmeng , Corley, Douglas A. , Peters, Ulrike , Song, Mingyang , Archambault, Alexi N , Harrison, Tabitha A , Bishop, D Timothy , Brenner, Hermann , Chan, Andrew T , Chang-Claude, Jenny , Figueiredo, Jane C , Gruber, Stephen B , Gunter, Marc J , Guo, Feng , Hoffmeister, Michael , Jenkins, Mark A , Marchand, Loïc Le , Moreno, Victor , Pai, R K , Rennert, Gad , Sakoda, Lori C , Song, Mingyang , Win, Aung K , Woods, Michael O , Murphy, Neil , Campbell, Peter T , Peterse, Elisabeth F P , Cao, Yin , Liang, Peter S , Hayes, Richard B , Jeon, Jihyoun , Lin, Yi , Jenkins, Mark A. , Keku, Temitope O , Marchand, Loı̈c Le , Moreno, Vı́ctor , Newcomb, Polly A. , Sakoda, Lori C. , Song, Mingyang , Murphy, Neil , Campbell, Peter T. , Su, Yu-Ru , Lansdorp‐Vogelaar, Iris , Zeleniuch‐Jacquotte, Anne , Liang, Peter S. , Hsu, Li , Hayes, Richard B.
JNCI: Journal of the National Cancer Institute | January 11, 2022 | Volume: No volume available | Issue: No issue available | Pages: No page available
AbstractBackgroundThe incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants.MethodsRelying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve.ResultsIncreasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores.ConclusionsPersonal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.