Prospective Study Reveals Associations Between Colorectal Cancer and Type 2 Diabetes Mellitus or Insulin Use in Men

Campbell, Peter T.; Deka, Anusila; Jacobs, Eric J.; Newton, Christina C.; Hildebrand, Janet S.; McCullough, Marjorie L.; Limburg, Paul J.; Gapstur, Susan M.

doi:10.1053/j.gastro.2010.06.072

Cited by 128 publications

(157 citation statements)

References 28 publications

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“…Importantly, insulin has been known to promote tumorigenesis, on which there has been recent controversy. 6,27 In addition, the evidence of potential anticancer effect of thiazolidinedione was reported in several studies. 28,29 However, when we adjusted for these variables in our analysis, use of metformin continued to be an independent factor of better outcome.…”

Section: Discussionmentioning

confidence: 98%

The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus

Lee

Kim

Jeon

et al. 2011

Intl Journal of Cancer

186

154

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Metformin use has been associated with decreased cancer risk and mortality. However, the effects of metformin on clinical outcomes of colorectal cancer (CRC) are not defined. This study aimed to evaluate the association between metformin use and mortality of CRC in diabetic patients. We identified 595 patients who were diagnosed both CRC and diabetes mellitus. Patients were compared by two groups; 258 diabetic patients taking metformin and 337 diabetic patients not taking metformin. Patient's demographics, clinical characteristics, overall mortality and CRC-specific mortality were analyzed. After a median follow-up of 41 months, there were 71 total deaths (27.5%) and 55 CRC-specific deaths (21.3%) among 258 patients who used metformin, compared with 136 total deaths (40.4%) and 104 CRC-specific deaths (30.9%) among 337 patients who did not use metformin. Metformin use was associated with decreased overall mortality (p 5 0.018) and CRC-specific mortality (p 5 0.042) by univariate analysis. After adjustment for clinically relevant factors, metformin use showed lower risk of overall mortality (HR, 0.66; 95% CI 0.47620.923; p 5 0.015) and CRC-specific mortality (HR, 0.66; 95% CI 0.4520.975; p 5 0.037) in CRC patients with diabetes. Metformin use in CRC patients with diabetes is associated with lower risk of CRC-specific and overall mortality.Colorectal cancer (CRC) is the third leading cause of cancerrelated death.

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Section: Discussionmentioning

confidence: 98%

The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus

Lee

Kim

Jeon

et al. 2011

Intl Journal of Cancer

186

154

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“…For the 1997 and all subsequent questionnaires (1999, 2001, 2003, and 2005), the diabetes question was modified to exclude diagnoses of gestational diabetes and participants were asked the year of their diabetes mellitus diagnosis. The duration of diabetes was estimated as described previously (20). On the 1992/93 questionnaire, participants were asked if they had ever used insulin and if so, for how many years.…”

Section: Assessment Of Diabetes Insulin Use and Other Risk Factorsmentioning

confidence: 99%

Type II Diabetes Mellitus and the Incidence of Epithelial Ovarian Cancer in the Cancer Prevention Study-II Nutrition Cohort

Gapstur

Patel

Diver

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Despite consistent associations of type II diabetes mellitus with hormonally related cancers such as breast and endometrium, the relation between type II diabetes mellitus and ovarian cancer risk is unclear.Methods: Associations of type II diabetes mellitus status, duration, and insulin use with epithelial ovarian cancer overall, and with serous and nonserous histologic subtypes were examined in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of U.S. men and women predominantly aged 50 years and older. Between 1992 and 2007, 524 incident epithelial ovarian cancer cases were identified among 63,440 postmenopausal women. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were computed using extended Cox regression to update diabetes status and bilateral oophorectomy status during follow-up.Results: Type II diabetes mellitus status (RR ¼ 1.05; 95% CI, 0.75-1.46) and duration were not associated with epithelial ovarian cancer risk. Although not statistically significantly different (P difference ¼ 0.39), the RR was higher for type II diabetes mellitus with insulin use (RR ¼ 1.28; 95% CI, 0.74-2.24) than for type II diabetes mellitus without insulin use (RR ¼ 0.96; 95% CI, 0.64-1.43). Diabetes seemed to be more strongly associated with nonserous (RR ¼ 1.41; 95% CI, 0.70-2.85) than serous (RR ¼ 0.71; 95% CI, 0.41-1.23) histologic subtypes.Conclusions: Type II diabetes mellitus was not associated with risk of epithelial ovarian cancer, although higher risks with nonserous subtypes and among insulin users cannot be ruled out.Impact: Larger studies are needed to clarify associations of type II diabetes mellitus with or without insulin use with risk of ovarian cancer overall and by histologic subtypes. Cancer Epidemiol Biomarkers Prev; 21(11); 2000-5. Ó2012 AACR.

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“…Many studies which examine the association between Type II DM and CRC published since the 2005 meta-analysis by Larsson, analyze statistics in men and women separately in the same study, which suggest that the association among women is not as significant relative to men. A more recent large, prospective cohort-study by Campbell et al demonstrated the association between Type II DM and CRC among men (RR 1.24, 95% CI 1.08-1.44), but not among women (RR 1.01, 95% CI 0.82-1.23) (Campbell et al, 2010). Limburg and colleagues have also supported a statistically significant relationship between Type II DM and CRC (especially proximal colon CRC vs. distal CRC) in men, but not statistically significant in women.…”

Section: Epidemiologic Studiesmentioning

confidence: 97%

“…While the pathogenesis of hyperglycemia in Type I DM is secondary to lack of insulin due to islet destruction, the hyperglycemia in Type II DM results from complex genetic interactions, the expression of which is modified by environmental factors such as increased age, reduced physical activity and obesity (Inzucchi & Sherwin, 2007). The over-production of insulin and the influence of hyperinsulinemia in enhancing free or bioavailable concentrations of insulin-like growth factor-1 (IGF-1) have been postulated to increase carcinogenesis through a tyrosine kinase growth factor cascade in enhancing tumor cell proliferation (Campbell et al, 2010;Giovannucci, 1995;McKeown-Eyssen, 1994;Moore, 1998). Type II DM has been demonstrated by numerous epidemiologic studies to be associated with increased risk of many gastrointestinal cancers: esophageal adenocarcinoma, colorectal cancer, pancreatic cancer, biliary tract cancers (primary gallbladder carcinoma, extrahepatic/intrahepatic cholangiocarcinoma) and hepatocellular carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Implications of Type II Diabetes Mellitus on Gastrointestinal Cancers

Yu¹,

Jamal²

2011

Recent Advances in the Pathogenesis, Prevention and Management of Type 2 Diabetes and Its Complications

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Prospective Study Reveals Associations Between Colorectal Cancer and Type 2 Diabetes Mellitus or Insulin Use in Men

Cited by 128 publications

References 28 publications

The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus

The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus

Type II Diabetes Mellitus and the Incidence of Epithelial Ovarian Cancer in the Cancer Prevention Study-II Nutrition Cohort

Implications of Type II Diabetes Mellitus on Gastrointestinal Cancers

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