Abstract
Background
Epidemiological evidence indicates that individuals with type 2 diabetes are at an increased risk of cancer. Elevated glucose levels, below the diagnostic threshold for diabetes, have also been suggested to be associated with increased cancer risks.
Methods
We investigated possible associations between glucose levels and the risk of breast, endometrial, and ovarian cancer in a cohort of more than 230,000 women, for which information on outcome and potential confounders was obtained by record linkage to population-based registers.
Results
Diabetes was associated with an increased risk of postmenopausal breast cancer (HR = 1.22, 95% CI 1.04–1.43). An indication of a slightly elevated breast cancer risk was also found in postmenopausal women with impaired glucose metabolism (HR = 1.11, 95% CI 0.96–1.28). Diabetes (HR = 1.46, 95% CI 1.09–1.96) and impaired glucose metabolism (HR = 1.41, 95% CI 1.08–1.85) were associated with an increased risk of endometrial cancer. No associations were found between glucose levels and ovarian cancer risk. Following adjustment for BMI, estimates were attenuated for endometrial cancer, while point estimates for breast and ovarian cancer remained essentially unchanged.
Conclusions
Our results indicate that glucose levels below the diagnostic threshold for diabetes modify the risk not only of endometrial cancer but possibly also of postmenopausal breast cancer.
Similar content being viewed by others
References
Strickler HD, Wylie-Rosett J, Rohan T et al (2001) The relation of type 2 diabetes and cancer. Diabetes Technol Ther 3:263–274
Giovannucci E, Harlan DM, Archer MC et al (2010) Diabetes and cancer: a consensus report. Diabetes Care 33:1674–1685
Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M (2005) Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 92:2076–2083
El-Serag HB, Hampel H, Javadi F (2006) The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 4:369–380
Larsson SC, Orsini N, Wolk A (2005) Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 97:1679–1687
Friberg E, Orsini N, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 50:1365–1374
Lindemann K, Vatten LJ, Ellstrom-Engh M, Eskild A (2008) Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study. Br J Cancer 98:1582–1585
Saltzman BS, Doherty JA, Hill DA et al (2008) Diabetes and endometrial cancer: an evaluation of the modifying effects of other known risk factors. Am J Epidemiol 167:607–614
Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B (2005) Diabetes mellitus and breast cancer. Lancet Oncol 6:103–111
Larsson SC, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 121:856–862
Xue F, Michels KB (2007) Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am J Clin Nutr 86:S823–S835
Adler AI, Weiss NS, Kamb ML, Lyon JL (1996) Is diabetes mellitus a risk factor for ovarian cancer? A case-control study in Utah and Washington (United States). Cancer Causes Control 7:475–478
Parazzini F, Moroni S, La Vecchia C, Negri E, dal Pino D, Bolis G (1997) Ovarian cancer risk and history of selected medical conditions linked with female hormones. Eur J Cancer 33:1634–1637
Wideroff L, Gridley G, Mellemkjaer L et al (1997) Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 89:1360–1365
Weiderpass E, Ye W, Vainio H, Kaaks R, Adami HO (2002) Diabetes mellitus and ovarian cancer (Sweden). Cancer Causes Control 13:759–764
Muti P, Quattrin T, Grant BJ et al (2002) Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomarkers Prev 11:1361–1368
Furberg AS, Thune I (2003) Metabolic abnormalities (hypertension, hyperglycemia and overweight), lifestyle (high energy intake and physical inactivity) and endometrial cancer risk in a Norwegian cohort. Int J Cancer 104:669–676
Saydah SH, Loria CM, Eberhardt MS, Brancati FL (2003) Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol 157:1092–1100
Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM (2005) Fasting serum glucose level and cancer risk in Korean men and women. Jama 293:194–202
Rapp K, Schroeder J, Klenk J et al (2006) Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 49:945–952
Dankner R, Chetrit A, Segal P (2007) Glucose tolerance status and 20 year cancer incidence. Isr Med Assoc J 9:592–596
Stattin P, Bjor O, Ferrari P et al (2007) Prospective study of hyperglycemia and cancer risk. Diabetes Care 30:561–567
Stocks T, Rapp K, Bjorge T et al (2009) Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (me-can): analysis of six prospective cohorts. PLoS Med 6(12):e1000201
Manjer J, Kaaks R, Riboli E, Berglund G (2001) Risk of breast cancer in relation to anthropometry, blood pressure, blood lipids and glucose metabolism: a prospective study within the Malmo preventive project. Eur J Cancer Prev 10:33–42
Mink PJ, Shahar E, Rosamond WD, Alberg AJ, Folsom AR (2002) Serum insulin and glucose levels and breast cancer incidence: the atherosclerosis risk in communities study. Am J Epidemiol 156:349–352
Kabat GC, Kim M, Caan BJ et al (2009) Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer. Int J Cancer 125:2704–2710
Cust AE, Kaaks R, Friedenreich C et al (2007) Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European prospective investigation into cancer and nutrition (EPIC). Endocr Relat Cancer 14:755–767
Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E (2001) High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 358:2026–2033
Barlow L, Westergren K, Holmberg L, Talback M (2009) The completeness of the Swedish cancer register: a sample survey for year 1998. Acta oncologica (Stockholm, Sweden) 48:27–33
Jungner I, Marcovina SM, Walldius G, Holme I, Kolar W, Steiner E (1998) Apolipoprotein B and A-I values in 147576 Swedish males and females, standardized according to the World Health Organization-international federation of clinical chemistry first international reference materials. Clin Chem 44:1641–1649
Statistics Sweden (2011) Swedish socio-economic classification (SEI). http://www.scb.se/Grupp/Hitta_statistik/Forsta_Statistik/Klassifikationer/_Dokument/SEI-AGG_Eng.pdf. Accessed 2011
Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nature Rev 8:915–928
Shaw RJ (2006) Glucose metabolism and cancer. Curr Opin Cell Biol 18:598–608
Bjorge T, Lukanova A, Jonsson H et al (2010) Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project. Cancer Epidemiol Biomarkers Prev 19:1737–1745
Hemminki K, Li X, Sundquist J, Sundquist K (2010) Risk of cancer following hospitalization for type 2 diabetes. Oncologist 15:548–555
Hamajima N, Hirose K, Tajima K et al (2002) Alcohol, tobacco and breast cancer–collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 87:1234–1245
Magnusson C, Wedren S, Rosenberg LU (2007) Cigarette smoking and breast cancer risk: a population-based study in Sweden. Br J Cancer 97:1287–1290
Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM (2006) Does smoking increase risk of ovarian cancer? A systematic review. Gynecol Oncol 103:1122–1129
Zhou B, Yang L, Sun Q et al (2008) Cigarette smoking and the risk of endometrial cancer: a meta-analysis. Am J Med 121:501–508
Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM (2009) New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 32:1620–1625
Smith U, Gale EA (2009) Does diabetes therapy influence the risk of cancer? Diabetologia 52:1699–1708
Pollak M (2010) Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res 3:1060–1065
Misra A (2009) Prevention of type 2 diabetes: the long and winding road. Lancet 374:1655–1656
Acknowledgments
The study was supported by grants from the Swedish Council for Working life and Social research (# 2007-214), Karolinska Institutet Funds, the Swedish Cancer Society (# 2007/0526, # CAN 2010/608), and the Gunnar and Ingmar Jungner Foundation for Laboratory Medicine (Stockholm). The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Conflict of interest
The authors declare no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lambe, M., Wigertz, A., Garmo, H. et al. Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer. Cancer Causes Control 22, 1163–1171 (2011). https://doi.org/10.1007/s10552-011-9794-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-011-9794-8