Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials

Frank A Sinicrope, Nathan R. Foster, Harry H Yoon, Thomas Christopher Smyrk, George P. Kim, Carmen J. Allegra, Greg Yothers, Daniel A. Nikcevich, Daniel J. Sargent

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Abstract

Purpose: Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown. Patients and Methods: BMI (kg/m 2) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively. Results: Overall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m 2). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients. Conclusion: Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.

Original languageEnglish (US)
Pages (from-to)406-412
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number4
DOIs
StatePublished - Feb 1 2012

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DNA Mismatch Repair
Adjuvant Chemotherapy
Colon
Obesity
Carcinoma
Body Mass Index
Colonic Neoplasms
Survival
Neoplasms
Logistic Models
Proportional Hazards Models
Disease-Free Survival
Odds Ratio
Weights and Measures
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials. / Sinicrope, Frank A; Foster, Nathan R.; Yoon, Harry H; Smyrk, Thomas Christopher; Kim, George P.; Allegra, Carmen J.; Yothers, Greg; Nikcevich, Daniel A.; Sargent, Daniel J.

In: Journal of Clinical Oncology, Vol. 30, No. 4, 01.02.2012, p. 406-412.

Research output: Contribution to journalArticle

Sinicrope, Frank A ; Foster, Nathan R. ; Yoon, Harry H ; Smyrk, Thomas Christopher ; Kim, George P. ; Allegra, Carmen J. ; Yothers, Greg ; Nikcevich, Daniel A. ; Sargent, Daniel J. / Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 4. pp. 406-412.
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abstract = "Purpose: Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown. Patients and Methods: BMI (kg/m 2) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively. Results: Overall, 427 (16{\%}) tumors showed deficient MMR (dMMR), and 630 patients (23{\%}) were obese (BMI ≥ 30 kg/m 2). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10{\%} v 17{\%}; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95{\%} CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8{\%} v 13{\%}; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95{\%} CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95{\%} CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients. Conclusion: Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.",
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T1 - Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials

AU - Sinicrope, Frank A

AU - Foster, Nathan R.

AU - Yoon, Harry H

AU - Smyrk, Thomas Christopher

AU - Kim, George P.

AU - Allegra, Carmen J.

AU - Yothers, Greg

AU - Nikcevich, Daniel A.

AU - Sargent, Daniel J.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Purpose: Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown. Patients and Methods: BMI (kg/m 2) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively. Results: Overall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m 2). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients. Conclusion: Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.

AB - Purpose: Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown. Patients and Methods: BMI (kg/m 2) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively. Results: Overall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m 2). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients. Conclusion: Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.

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