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      Diabetes, Obesity, and the Metabolic Syndrome as Prognostic Factors in Stages I to III Colorectal Cancer Patients

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          Abstract

          Attempts to introduce prognostic factors for survival outcomes in localized colorectal cancer patients receiving surgical treatment with or without adjuvant therapies, beyond the classic staging parameters, have been met with limited success. Obesity and diabetes mellitus are among the conditions that predispose to colorectal cancer but their value as prognostic markers once the disease is diagnosed is controversial.

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          Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events.

          Alireza Moghaddam, Mark Woodward, Rachel Huxley (2007)
          Colorectal cancer is the second most common cause of death and illness in developed countries. Previous reviews have suggested that obesity may be associated with 30% to 60% greater risk of colorectal cancer, but little consideration was given to the possible effect of publication bias on the reported association. Relevant studies were identified through EMBASE and MEDLINE. Studies were included if they had published quantitative estimates of the association between general obesity [defined here as body mass index (BMI) > or = 30 kg/m(2)] and central obesity (measured using waist circumference) and colorectal cancer. Random-effects meta-analyses were done, involving 70,000 cases of incident colorectal cancer from 31 studies, of which 23 were cohort studies and 8 were case-control studies. After pooling and correcting for publication bias, the estimated relative risk of colorectal cancer was 1.19 [95% confidence interval (95% CI), 1.11-1.29], comparing obese (BMI > or = 30 kg/m(2)) with normal weight (BMI <25 kg/m(2)) people; and 1.45 (95% CI, 1.31-1.61), comparing those with the highest, to the lowest, level of central obesity. After correcting for publication bias, the risk of colorectal cancer was 1.41 (95% CI, 1.30-1.54) in men compared with 1.08 (95% CI, 0.98-1.18) for women (P(heterogeneity) <0.001). There was evidence of a dose-response relationship between BMI and colorectal cancer: for a 2 kg/m(2) increase in BMI, the risk of colorectal cancer increased by 7% (4-10%). For a 2-cm increase in waist circumference, the risk increased by 4% (2-5%). Obesity has a direct and independent relationship with colorectal cancer, although the strength of the association with general obesity is smaller than previously reported.
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            Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer?

            Hiroki Yuhara, Craig Steinmaus, Stephanie Cohen … (2011)
            Diabetes mellitus (DM) has been associated with an increased risk of colorectal cancer (CRC). The American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008 recommend that clinicians be aware of an increased CRC risk in patients with smoking and obesity, but do not highlight the increase in CRC risk in patients with DM. To provide an updated quantitative assessment of the association of DM with colon cancer (CC) and rectal cancer (RC), we conducted a meta-analysis of case-control and cohort studies. We also evaluated whether the association varied by sex, and assessed potential confounders including obesity, smoking, and exercise. We identified studies by searching the EMBASE and MEDLINE databases (from inception through 31 December 2009) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias. DM was associated with an increased risk of CC (summary RR 1.38, 95% CI 1.26-1.51; n=14 studies) and RC (summary RR 1.20, 95% CI 1.09-1.31; n=12 studies). The association remained when we limited the meta-analysis to studies that either controlled for smoking and obesity, or for smoking, obesity, and physical exercise. DM was associated with an increased risk of CC for both men (summary RR 1.43, 95% CI 1.30-1.57; n=11 studies) and women (summary RR 1.35, 95% CI 1.14-1.53; n=10 studies). For RC, there was a significant association between DM and cancer risk for men (summary RR 1.22, 95% CI 1.07-1.40; n=8 studies), but not for women (summary RR 1.09, 95% CI=0.99-1.19; n=8 studies). These data suggest that DM is an independent risk factor for colon and rectal cancer. Although these findings are based on observational epidemiological studies that have inherent limitations due to diagnostic bias and confounding, subgroup analyses confirmed the consistency of our findings across study type and population. This information can inform risk models and specialty society CRC screening guidelines.
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              Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer.

              Blase Polite, Peter C Raich, Norman Wolmark … (2006)
              Although several studies have established a link between obesity and colon cancer risk, little is known about the effect of obesity on outcomes after diagnosis. We investigated the association of body mass index (BMI) with outcomes after colon cancer in patients from cooperative group clinical trials. The study cohort consisted of 4288 patients with Dukes B and C colon cancer who were accrued from July 1989 to February 1994 to National Surgical Adjuvant Breast and Bowel Project randomized trials. Risk of recurrence, second primary cancer, and mortality (overall and by likely cause) were evaluated in relation to BMI at diagnosis using statistical modeling. Median follow-up time was 11.2 years. All statistical tests were two-sided. Very obese patients (BMI > or = 35 kg/m2) had greater risk of a colon cancer event (recurrence or secondary primary tumor; hazard ratio [HR] = 1.38, 95% confidence interval [CI] = 1.10 to 1.73) than normal weight patients (BMI = 18.5-24.9 kg/m2). Mortality was greater for very obese (HR = 1.28, 95% CI = 1.04 to 1.57) and underweight (BMI < 18.5 kg/m2) (HR = 1.49, 95% CI = 1.17 to 1.91) than for normal weight patients. The increased risk of mortality for underweight patients was dominated by non-colon cancer deaths (HR of such deaths compared with normal weight patients = 2.23, 95% CI = 1.50 to 3.31), whereas for the very obese, deaths likely due to colon cancer were increased (HR = 1.36, 95% CI = 1.06 to 1.73). Among colon cancer patients, a BMI greater than 35.0 kg/m2 at diagnosis was associated with an increased risk for recurrence of and death from colon cancer. Further studies are needed to determine pathways between obesity and recurrence risk and whether weight reduction or related interventions would improve prognosis.
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                Author and article information

                Journal
                Title: Journal of Gastrointestinal Cancer
                Abbreviated Title: J Gastrointest Canc
                Publisher: Springer Science and Business Media LLC
                ISSN (Print): 1941-6628
                ISSN (Electronic): 1941-6636
                Publication date Created: June 2019
                Publication date (Electronic): January 15 2018
                Publication date (Print): June 2019
                Volume: 50
                Issue: 2
                Pages: 221-229
                Article
                DOI: 10.1007/s12029-018-0056-9
                PubMed ID: 29335847
                SO-VID: d3685662-6b5a-4a51-84c4-af7c84d1f4c0
                Copyright © © 2019
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                http://www.springer.com/tdm

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