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Diabetes Mellitus and Cancer Risk in a Network of Case-Control Studies

Bosetti, Cristina, Rosato, Valentina, Polesel, Jerry, Levi, Fabio, Talamini, Renato, Montella, Maurizio, Negri, Eva, Tavani, Alessandra, Zucchetto, Antonella, Franceschi, Silvia, Corrao, Giovanni, Vecchia, Carlo La
Nutrition and cancer 2012 v.64 no.5 pp. 643-651
alcoholic beverages, animal ovaries, case-control studies, confidence interval, diabetes mellitus, education, endometrium, esophagus, hormone replacement therapy, larynx, liver, men, mouth, neoplasms, oral contraceptives, pancreas, pharynx, postmenopause, regression analysis, risk, smoking (habit), women, Italy, Switzerland
Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without—adjusted for major identified confounding factors for the cancers considered through logistic regression models—were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer.TABLE 1 Number of cases of selected cancer sites and controls and corresponding median age in Italy and Switzerland, 1991–2009CasesMedianControlsMedianCancer site (References)(men/women)age (yr)(men/women)age (yr)Oral cavity and pharynx (10,11)1190/278582553/120858Esophagus (12,13)438/6760919/34060Gastric (14)143/8763286/26163Colorectum (15,16)1401/989622586/235758Liver (17)149/3666278/12665Pancreas (18)174/15263348/30463Larynx (19)770/82621564/40661Breast (20,21)–/303455–/339256Endometrium (22)–/60762–/136661Ovary (23)–/103156–/241157Prostate (24)1294/–661451/–63Renal cell cancer (25)494/27362988/54662TABLE 2 Distribution of cases of selected cancer sites and corresponding controls, and odds ratios (OR) and 95% confidence intervals (CI) according to history of diabetes in Italy and Switzerland, 1991–2009History of diabetesNoYesCancer siteCases(%)Controls(%)Cases(%)Controls(%)ORᵃ (95% CI)ORᵇ (95% CI)Oral cavity and pharynx1370(93.3)3580(95.2)98(6.7)181(4.8)1.34 (0.98–1.85)1.58 (1.15–2.18)Esophagus455(90.1)1197(95.1)50(9.9)62(4.9)2.22 (1.36–3.63)2.52 (1.54–4.13)Gastric213(92.6)504(92.1)17(7.4)43(7.9)0.94 (0.51–1.73)0.98 (0.53–1.81)Colorectum2229(93.3)4722(95.5)161(6.7)221(4.5)1.23 (0.99–1.53)1.23 (0.98–1.53) Colon1371(93.7)4722(95.5)92(6.3)221(4.5)1.17 (0.90–1.52)1.16 (0.89–1.50) Rectum858(92.6)4722(95.5)69(7.4)221(4.5)1.36 (1.02–1.83)1.38 (1.03–1.86)Liver145(78.4)377(93.3)40(21.6)27(6.7)3.42 (1.89–6.18)3.52 (1.94–6.39)Pancreas269(82.5)615(94.3)57(17.5)37(5.7)3.18 (1.95–5.20)3.32 (2.02–5.44)Larynx782(91.8)1836(93.2)70(8.2)134(6.8)1.23 (0.86–1.74)1.30 (0.91–1.85)Breast/pre–perimenopauseᶜ1134(98.6)1165(98.7)16(1.4)15(1.3)1.35 (0.64–2.86)1.50 (0.70–3.21)Breast/postmenopauseᶜ1750(92.9)2103(95.1)134(7.1)109(4.9)1.83 (1.39–2.40)1.76 (1.34–2.32)Endometriumᵈ545(89.8)1300(95.2)62(10.2)66(4.8)2.08 (1.41–3.06)1.70 (1.14–2.53)Ovaryᵈ986(95.6)2324(96.4)45(4.4)87(3.6)1.24 (0.82–1.86)1.21 (0.80–1.82)Prostate1205(93.1)1352(93.2)89(6.9)99(6.8)0.91 (0.66–1.26)0.92 (0.66–1.27)Renal cell697(90.9)1423(92.8)70(9.1)111(7.2)1.30 (0.94–1.80)1.26 (0.91–1.75)ᵃEstimates from logistic regression model adjusted for sex (when appropriate), age, study center, year of interview, education, alcohol drinking, and tobacco smoking. Reference category: no history of diabetes.ᵇFurther adjusted for body mass index.ᶜFurther adjusted for age at first birth, parity, age at menopause (when appropriate), oral contraceptives use, and hormone replacement therapy use.ᵈFurther adjusted for parity, menopausal status, age at menopause, oral contraceptives use, and hormone replacement therapy use.