Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status

Peter T. Campbell, Elizabeth T. Jacobs, Cornelia M. Ulrich, Jane C. Figueiredo, Jenny N. Poynter, John R. McLaughlin, Robert W. Haile, Eric J. Jacobs, Polly A. Newcomb, John D. Potter, Loïc Le Marchand, Roger C. Green, Patrick Parfrey, H. Banfield Younghusband, Michelle Cotterchio, Steven Gallinger, Mark A. Jenkins, John L. Hopper, John A. Baron, Stephen N ThibodeauNoralane Morey Lindor, Paul John Limburg, María Elena Martínez

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Abstract

Background Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.Methods The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (≥30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided.Results Recent BMI, modeled in 5 kg/m 2 increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P =. 22). Recent BMI, per 5 kg/m2, was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31).Conclusion The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.

Original languageEnglish (US)
Pages (from-to)391-400
Number of pages10
JournalJournal of the National Cancer Institute
Volume102
Issue number6
DOIs
StatePublished - Mar 2010

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Microsatellite Instability
Case-Control Studies
Colorectal Neoplasms
Obesity
Odds Ratio
Confidence Intervals
Body Mass Index
Neoplasms
Microsatellite Repeats
Weights and Measures
Self Report
Registries
Siblings
Logistic Models
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Campbell, P. T., Jacobs, E. T., Ulrich, C. M., Figueiredo, J. C., Poynter, J. N., McLaughlin, J. R., ... Martínez, M. E. (2010). Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status. Journal of the National Cancer Institute, 102(6), 391-400. https://doi.org/10.1093/jnci/djq011

Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status. / Campbell, Peter T.; Jacobs, Elizabeth T.; Ulrich, Cornelia M.; Figueiredo, Jane C.; Poynter, Jenny N.; McLaughlin, John R.; Haile, Robert W.; Jacobs, Eric J.; Newcomb, Polly A.; Potter, John D.; Le Marchand, Loïc; Green, Roger C.; Parfrey, Patrick; Younghusband, H. Banfield; Cotterchio, Michelle; Gallinger, Steven; Jenkins, Mark A.; Hopper, John L.; Baron, John A.; Thibodeau, Stephen N; Lindor, Noralane Morey; Limburg, Paul John; Martínez, María Elena.

In: Journal of the National Cancer Institute, Vol. 102, No. 6, 03.2010, p. 391-400.

Research output: Contribution to journalArticle

Campbell, PT, Jacobs, ET, Ulrich, CM, Figueiredo, JC, Poynter, JN, McLaughlin, JR, Haile, RW, Jacobs, EJ, Newcomb, PA, Potter, JD, Le Marchand, L, Green, RC, Parfrey, P, Younghusband, HB, Cotterchio, M, Gallinger, S, Jenkins, MA, Hopper, JL, Baron, JA, Thibodeau, SN, Lindor, NM, Limburg, PJ & Martínez, ME 2010, 'Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status', Journal of the National Cancer Institute, vol. 102, no. 6, pp. 391-400. https://doi.org/10.1093/jnci/djq011
Campbell, Peter T. ; Jacobs, Elizabeth T. ; Ulrich, Cornelia M. ; Figueiredo, Jane C. ; Poynter, Jenny N. ; McLaughlin, John R. ; Haile, Robert W. ; Jacobs, Eric J. ; Newcomb, Polly A. ; Potter, John D. ; Le Marchand, Loïc ; Green, Roger C. ; Parfrey, Patrick ; Younghusband, H. Banfield ; Cotterchio, Michelle ; Gallinger, Steven ; Jenkins, Mark A. ; Hopper, John L. ; Baron, John A. ; Thibodeau, Stephen N ; Lindor, Noralane Morey ; Limburg, Paul John ; Martínez, María Elena. / Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status. In: Journal of the National Cancer Institute. 2010 ; Vol. 102, No. 6. pp. 391-400.
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abstract = "Background Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10{\%}-20{\%} of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.Methods The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7{\%} of the case subjects and classified as microsatellite (MS)-stable (0{\%} of markers unstable; n = 913), MSI-low (>0{\%} but <30{\%} of markers unstable; n = 149), or MSI-high (≥30{\%} of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95{\%} confidence intervals (95{\%} CIs). All statistical tests were two-sided.Results Recent BMI, modeled in 5 kg/m 2 increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95{\%} CI = 1.15 to 1.34), for women only (OR = 1.20; 95{\%} CI = 1.10 to 1.32), and for men only (OR = 1.30; 95{\%} CI = 1.15 to 1.47). There was no interaction with sex (P =. 22). Recent BMI, per 5 kg/m2, was positively associated with the risk of MS-stable (OR = 1.38; 95{\%} CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95{\%} CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95{\%} CI = 0.84 to 1.31).Conclusion The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.",
author = "Campbell, {Peter T.} and Jacobs, {Elizabeth T.} and Ulrich, {Cornelia M.} and Figueiredo, {Jane C.} and Poynter, {Jenny N.} and McLaughlin, {John R.} and Haile, {Robert W.} and Jacobs, {Eric J.} and Newcomb, {Polly A.} and Potter, {John D.} and {Le Marchand}, Lo{\"i}c and Green, {Roger C.} and Patrick Parfrey and Younghusband, {H. Banfield} and Michelle Cotterchio and Steven Gallinger and Jenkins, {Mark A.} and Hopper, {John L.} and Baron, {John A.} and Thibodeau, {Stephen N} and Lindor, {Noralane Morey} and Limburg, {Paul John} and Mart{\'i}nez, {Mar{\'i}a Elena}",
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TY - JOUR

T1 - Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status

AU - Campbell, Peter T.

AU - Jacobs, Elizabeth T.

AU - Ulrich, Cornelia M.

AU - Figueiredo, Jane C.

AU - Poynter, Jenny N.

AU - McLaughlin, John R.

AU - Haile, Robert W.

AU - Jacobs, Eric J.

AU - Newcomb, Polly A.

AU - Potter, John D.

AU - Le Marchand, Loïc

AU - Green, Roger C.

AU - Parfrey, Patrick

AU - Younghusband, H. Banfield

AU - Cotterchio, Michelle

AU - Gallinger, Steven

AU - Jenkins, Mark A.

AU - Hopper, John L.

AU - Baron, John A.

AU - Thibodeau, Stephen N

AU - Lindor, Noralane Morey

AU - Limburg, Paul John

AU - Martínez, María Elena

PY - 2010/3

Y1 - 2010/3

N2 - Background Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.Methods The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (≥30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided.Results Recent BMI, modeled in 5 kg/m 2 increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P =. 22). Recent BMI, per 5 kg/m2, was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31).Conclusion The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.

AB - Background Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.Methods The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (≥30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided.Results Recent BMI, modeled in 5 kg/m 2 increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P =. 22). Recent BMI, per 5 kg/m2, was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31).Conclusion The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.

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DO - 10.1093/jnci/djq011

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