Serum glucose and risk of cancer: a meta-analysis

BMC Cancer

Danielle J Crawley²  Lars Holmberg⁴  Jennifer C Melvin³  Massimo Loda¹  Simon Chowdhury²  Sarah M Rudman²  Mieke Van Hemelrijck³ 

[1] Pathology, Dana-Farber Cancer Institute, Boston, MA, USA

[2] Department of Oncology, Guy’s & St Thomas’ NHS Foundation Trust, London, UK

[3] King’s College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Group, London, UK

[4] Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

关键词: Diabetes;    Meta-analysis;    Metabolic syndrome;    Cancer;    Glucose;   

Others  :  1106815
DOI  :  10.1186/1471-2407-14-985

 received in 2014-04-29, accepted in 2014-12-09,  发布年份 2014

【 摘 要 】

Background

Raised serum glucose has been linked to increased risk of many solid cancers. We performed a meta-analysis to quantify and summarise the evidence for this link.

Methods

Pubmed and Embase were reviewed, using search terms representing serum glucose and cancer. Inclusion and exclusion criteria focused on epidemiological studies with clear definitions of serum glucose levels, cancer type, as well as well-described statistical methods with sufficient data available. We used 6.1 mmol/L as the cut-off for high glucose, consistent with the WHO definition of metabolic syndrome. Random effects analyses were performed to estimate the pooled relative risk (RR).

Results

Nineteen studies were included in the primary analysis, which showed a pooled RR of 1.32 (95% CI: 1.20 – 1.45). Including only those individuals with fasting glucose measurements did not have a large effect on the pooled RR (1.32 (95% CI: 1.11-1.57). A stratified analysis showed a pooled RR of 1.34 (95% CI: 1.02-1.77) for hormonally driven cancer and 1.21 (95% CI: 1.09-1.36) for cancers thought to be driven by Insulin Growth Factor-1.

Conclusion

A positive association between serum glucose and risk of cancer was found. The underlying biological mechanisms remain to be elucidated but our subgroup analyses suggest that the insulin- IGF-1 axis does not fully explain the association. These findings are of public health importance as measures to reduce serum glucose via lifestyle and dietary changes could be implemented in the context of cancer mortality.

【 授权许可】

   
2014 Crawley et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njølstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J, Emerging Risk Factors C: Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 2011, 364(9):829-841.
• [2]Hirakawa Y, Ninomiya T, Mukai N, Doi Y, Hata J, Fukuhara M, Iwase M, Kitazono T, Kiyohara Y: Association between glucose tolerance level and cancer death in a general Japanese population: the Hisayama Study. Am J Epidemiol 2012, 176(10):856-864.
• [3]Dankner R, Chetrit A, Segal P: Glucose tolerance status and 20 year cancer incidence. Isr Med Assoc J: IMAJ 2007, 9(8):592-596.
• [4]Boyle P, Koechlin A, Pizot C, Boniol M, Robertson C, Mullie P, Bolli G, Rosenstock J, Autier P: Blood glucose concentrations and breast cancer risk in women without diabetes: a meta-analysis. Eur J Nutr 2013, 52(5):1533-1540.
• [5]Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM: Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005, 293(2):194-202.
• [6]Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D: Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care 2012, 35(11):2402-2411.
• [7]Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V, Foti D, Chiefari E, Brunetti A: Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res 2012, 2012:789174.
• [8]Renehan AG, Frystyk J, Flyvbjerg A: Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab: TEM 2006, 17(8):328-336.
• [9]Stattin P, Bylund A, Rinaldi S, Biessy C, Dechaud H, Stenman UH, Egevad L, Riboli E, Hallmans G, Kaaks R: Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J Natl Cancer Inst 2000, 92(23):1910-1917.
• [10]Guo Y, Xu F, Lu T, Duan Z, Zhang Z: Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev 2012, 38(7):904-910.
• [11]Radhakrishnan P, Chachadi V, Lin MF, Singh R, Kannagi R, Cheng PW: TNFalpha enhances the motility and invasiveness of prostatic cancer cells by stimulating the expression of selective glycosyl- and sulfotransferase genes involved in the synthesis of selectin ligands. Biochem Biophys Res Commun 2011, 409(3):436-441.
• [12]Flores MB, Rocha GZ, Damas-Souza DM, Osorio-Costa F, Dias MM, Ropelle ER, Camargo JA, de Carvalho RB, Carvalho HF, Saad MJ, Carvalheira JB: Obesity-induced increase in tumor necrosis factor-alpha leads to development of colon cancer in mice. Gastroenterology 2012, 143(3):741-753. e741-744
• [13]Hursting SD, Hursting MJ: Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer. Arterioscler Thromb Vasc Biol 2012, 32(8):1766-1770.
• [14]Gallagher EJ, Leroith D: Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care 2013, 36(Suppl 2):S233-S239.
• [15]Braun S, Bitton-Worms K, LeRoith D: The link between the metabolic syndrome and cancer. Int J Biol Sci 2011, 7(7):1003-1015.
• [16]Airley RE, Mobasheri A: Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy 2007, 53(4):233-256.
• [17]Moher D, Liberati A, Tetzlaff J, Altman DG, Group P: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009, 6(7):e1000097.
• [18]Stocks T, Rapp K, Bjorge T, Manjer J, Ulmer H, Selmer R, Lukanova A, Johansen D, Concin H, Tretli S, Hallmans G, Jonsson H, Stattin P: 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 2009, 6(12):e1000201.
• [19]Haggstrom C, Stocks T, Nagel G, Manjer J, Bjorge T, Hallmans G, Engeland A, Ulmer H, Lindkvist B, Selmer R, Concin H, Tretli S, Jonsson H, Stattin P: Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations. Epidemiology 2014, 25(6):823-828.
• [20]Friberg E, Orsini N, Mantzoros CS, Wolk A: Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 2007, 50(7):1365-1374.
• [21]Larsson SC, Mantzoros CS, Wolk A: Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 2007, 121(4):856-862.
• [22]Jiang Y, Ben Q, Shen H, Lu W, Zhang Y, Zhu J: Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies. Eur J Epidemiol 2011, 26(11):863-876.
• [23]Kulendran M, Salhab M, Mokbel K: Oestrogen-synthesising enzymes and breast cancer. Anticancer Res 2009, 29(4):1095-1109.
• [24]Harbord RM: Updated stests for small-study effects in meta-analyses. Stata Press 2009, 9(2):197-210.
• [25]Gwack J, Hwang SS, Ko KP, Jun JK, Park SK, Chang SH, Shin HR, Yoo KY: [Fasting serum glucose and subsequent liver cancer risk in a Korean prospective cohort]. J Prev Med Publ Health = Yebang Uihakhoe chi 2007, 40(1):23-28.
• [26]Park SM, Lim MK, Shin SA, Yun YH: Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: National Health Insurance Corporation Study. J Clin Oncol : Off J Am Soc Clin Oncol 2006, 24(31):5017-5024.
• [27]Zamboni PF, Simone M, Passaro A, Doh Dalla Nora E, Fellin R, Solini A: Metabolic profile in patients with benign prostate hyperplasia or prostate cancer and normal glucose tolerance. Horm Metab Res 2003, 35(5):296-300.
• [28]Burzawa J, Schmeler K, Soliman P, Lacour R, Meyer L, Huang M, Bevers M, Frumovitz M, Pustilnik T, Brown J, Anderson M, Ramondetta L, Tortolero-Luna G, Urbauer D, Zhang Q, Broaddus R, Chang S, Gershenson D, Lu K: Evaluation of insulin resistance among endometrial cancer patients. Gynecol Oncol 2012, 127:S8.
• [29]Loh WJ, North BV, Johnston DG, Godsland IF: Insulin resistance-related biomarker clustering and subclinical inflammation as predictors of cancer mortality during 21.5 years of follow-up. Cancer Causes Control: CCC 2010, 21(5):709-718.
• [30]Key TJ: Hormones and cancer in humans. Mutat Res 1995, 333(1–2):59-67.
• [31]Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Manson JE, Li J, Harris TG, Rohan TE, Xue X, Ho GY, Einstein MH, Kaplan RC, Burk RD, Wylie-Rosett J, Pollak MN, Anderson G, Howard BV, Strickler HD: A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev 2008, 17(4):921-929.
• [32]Mink PJ, Shahar E, Rosamond WD, Alberg AJ, Folsom AR: Serum insulin and glucose levels and breast cancer incidence: the atherosclerosis risk in communities study. Am J Epidemiol 2002, 156(4):349-352.
• [33]Furberg AS, Thune I: Metabolic abnormalities (hypertension, hyperglycemia and overweight), lifestyle (high energy intake and physical inactivity) and endometrial cancer risk in a Norwegian cohort. Int J Cancer 2003, 104(6):669-676.
• [34]Sung J, Park M, Kim H, Lee C, Park S, Moon W: J Gastroenterol Hepatol. 2012, 27(418):0815-9319.
• [35]Manjer J, Kaaks R, Riboli E, Berglund G: 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 2001, 10(1):33-42.
• [36]Friedenreich CM, Langley AR, Speidel TP, Lau DC, Courneya KS, Csizmadi I, Magliocco AM, Yasui Y, Cook LS: Case–control study of markers of insulin resistance and endometrial cancer risk. Endocr Relat Cancer 2012, 19(6):785-792.
• [37]Hubbard JS, Rohrmann S, Landis PK, Metter EJ, Muller DC, Andres R, Carter HB, Platz EA: Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging. Urology 2004, 63(2):253-258.
• [38]Ollberding N, Cheng I, Wilkens L, Henderson B, Pollak M, Kolonel L, Le Marchand L: Genetic variants, prediagnostic circulating levels of insulin-like growth factors, insulin, and glucose and the risk of colorectal cancer: the Multiethnic Cohort study. Cancer Epidemiol Biomarkers Prev 2012, 21(5):810-820.
• [39]Haggstrom C, Stocks T, Ulmert D, Bjorge T, Ulmer H, Hallmans G, Manjer J, Engeland A, Nagel G, Almqvist M, Selmer R, Concin H, Tretli S, Jonsson H, Stattin P: Prospective study on metabolic factors and risk of prostate cancer. Cancer 2012, 118(24):6199-6206.
• [40]Borena W, Strohmaier S, Lukanova A, Bjorge T, Lindkvist B, Hallmans G, Edlinger M, Stocks T, Nagel G, Manjer J, Engeland A, Selmer R, Häggström C, Tretli S, Concin H, Jonsson H, Stattin P, Ulmer H: Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults. Int J Cancer 2012, 131(1):193-200.
• [41]Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L: Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol 2008, 61(10):991-996.
• [42]Harbord RM: Updated tests for small effects in meta-analyses. Stata Press 2009, 9(2):197-210.
• [43]Margel D, Urbach DR, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner N: Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes. J Clin Oncol 2013, 31(25):3069-3075.
• [44]Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Howard BV, Wylie-Rosett J, Anderson GL, Ho GY, Kaplan RC, Li J, Xue X, Harris TG, Burk RD, Strickler HD: Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal women. Cancer Res 2008, 68(1):329-337.
• [45]Yun JE, Jo I, Park J, Kim MT, Ryu HG, Odongua N, Kim E, Jee SH: Cigarette smoking, elevated fasting serum glucose, and risk of pancreatic cancer in Korean men. Int J Cancer 2006, 119(1):208-212.
• [46]Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schunemann HJ, Ram M, Freudenheim JL, Sieri S, Trevisan M, Berrino F: Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomarkers Prev 2002, 11(11):1361-1368.
• [47]Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK: Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 2006, 49(5):945-952.
• [48]Stattin P, Bjor O, Ferrari P, Lukanova A, Lenner P, Lindahl B, Hallmans G, Kaaks R: Prospective study of hyperglycemia and cancer risk. Diabetes Care 2007, 30(3):561-567.
• [49]Stocks T, Lukanova A, Rinaldi S, Biessy C, Dossus L, Lindahl B, Hallmans G, Kaaks R, Stattin P: Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden. Int J Cancer 2007, 120(12):2678-2686.
• [50]Lambe M, Wigertz A, Garmo H, Walldius G, Jungner I, Hammar N: Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer. Cancer Causes Control: CCC 2011, 22(8):1163-1171.
• [51]Stocks T, Lukanova A, Johansson M, Rinaldi S, Palmqvist R, Hallmans G, Kaaks R, Stattin P: Components of the metabolic syndrome and colorectal cancer risk; a prospective study. Int J Obes 2008, 32(2):304-314.
• [52]Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stampfer MJ: Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 1999, 91(7):620-625.
• [53]de Santana IA, Moura GS, Vieira NF, Cipolotti R: Metabolic syndrome in patients with prostate cancer. Sao Paulo Med J 2008, 126(5):274-278.
• [54]Jun JK, Gwack J, Park SK, Choi YH, Kim Y, Shin A, Chang SH, Shin HR, Yoo KY: [Fasting serum glucose level and gastric cancer risk in a nested case–control study]. J Prev Med Public Health 2006, 39(6):493-498.
• [55]Walker K, Bratton DJ, Frost C: Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis. Br J Cancer 2011, 105(9):1451-1457.
• [56]Darbinian JA, Ferrara AM, Van Den Eeden SK, Quesenberry CP Jr, Fireman B, Habel LA: Glycemic status and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2008, 17(3):628-635.
• [57]Berrington de Gonzalez A, Yun JE, Lee SY, Klein AP, Jee SH: Pancreatic cancer and factors associated with the insulin resistance syndrome in the Korean cancer prevention study. Cancer Epidemiol Biomarkers Prev 2008, 17(2):359-364.
• [58]Ehrmann-Josko A, Sieminska J, Gornicka B, Ziarkiewicz-Wroblewska B, Ziolkowski B, Muszynski J: Impaired glucose metabolism in colorectal cancer. Scand J Gastroenterol 2006, 41(9):1079-1086.
• [59]Ozasa K, Ito Y, Suzuki K, Watanabe Y, Kojima M, Suzuki S, Tokudome S, Tamakoshi K, Toyoshima H, Kawado M, Hashimoto S, Hayakawa N, Wakai K, Tamakoshi A, JACC Study Group: Glucose intolerance and colorectal cancer risk in a nested case–control study among Japanese People. J Epidemiol 2005, 15(Suppl 2):S180-S184.
• [60]Tsushima M, Nomura AM, Lee J, Stemmermann GN: Prospective study of the association of serum triglyceride and glucose with colorectal cancer. Dig Dis Sci 2005, 50(3):499-505.
• [61]Suehiro T, Matsumata T, Shikada Y, Sugimachi K: Hyperinsulinemia in patients with colorectal cancer. Hepatogastroenterology 2005, 52(61):76-78.
• [62]Krajcik RA, Borofsky ND, Massardo S, Orentreich N: Insulin-like growth factor I (IGF-I), IGF-binding proteins, and breast cancer. Cancer Epidemiol Biomarkers Prev 2002, 11(12):1566-1573.
• [63]Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A: Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 2000, 283(19):2552-2558.
• [64]Spyridopoulos TN, Dessypris N, Antoniadis AG, Gialamas S, Antonopoulos CN, Katsifoti K, Adami HO, Chrousos GP, Petridou ET, Obesity and Cancer Oncology Group: Insulin resistance and risk of renal cell cancer: a case–control study. Hormones 2012, 11(3):308-315.
• [65]Singh S, Gahlot A, Pandey M, Pradhan S: Endocr Rev. 2012, 33/3:0163-0769X.
• [66]Simon D, Lange C, Charles M: Balkau B: Diabetes care. 2011, 60(A359):0012-1797.
• [67]Saydah SH, Loria CM, Eberhardt MS, Brancati FL: Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol 2003, 157(12):1092-1100.
• [68]Nilsen TI, Vatten LJ: Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis. Br J Cancer 2001, 84(3):417-422.
• [69]Lawlor DA, Smith GD, Ebrahim S: Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women’s Heart and Health Study. Cancer Causes Control : CCC 2004, 15(3):267-275.
• [70]Saydah SH, Platz EA, Rifai N, Pollak MN, Brancati FL, Helzlsouer KJ: Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2003, 12(5):412-418.
• [71]Nandeesha H, Koner BC, Dorairajan LN: Altered insulin sensitivity, insulin secretion and lipid profile in non-diabetic prostate carcinoma. Acta Physiol Hung 2008, 95(1):97-105.
• [72]Online calculator tool http://www.socbdr.org/rds/authors/unit_tables_conversions_and_genetic_dictionaries/conversion_in_si_units webcite
• [73]Alberti KG, Zimmet PZ: The reference is : Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998, 15(7):539-53.
• [74]Smith GD, Gunnell D, Holly J: Cancer and insulin-like growth factor-I. A potential mechanism linking the environment with cancer risk. BMJ 2000, 321(7265):847-848.
• [75]Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M: Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 1998, 351(9113):1393-1396.
• [76]Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M: Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998, 279(5350):563-566.
• [77]Yun SJ, Min BD, Kang HW, Shin KS, Kim TH, Kim WT, Lee SC, Kim WJ: Elevated insulin and insulin resistance are associated with the advanced pathological stage of prostate cancer in Korean population. J Korean Med Sci 2012, 27(9):1079-1084.
• [78]Albanes D, Weinstein SJ, Wright ME, Mannisto S, Limburg PJ, Snyder K, Virtamo J: Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J Natl Cancer Inst 2009, 101(18):1272-1279.
• [79]Chung YW, Han DS, Park YK, Son BK, Paik CH, Lee HL, Jeon YC, Sohn JH: Association of obesity, serum glucose and lipids with the risk of advanced colorectal adenoma and cancer: a case–control study in Korea. Dig Liver Dis 2006, 38(9):668-672.
• [80]Hsing AW, Gao YT, Chua S Jr, Deng J, Stanczyk FZ: Insulin resistance and prostate cancer risk. J Natl Cancer Inst 2003, 95(1):67-71.
• [81]Wulaningsih W, Holmberg L, Garmo H, Zethelius B, Wigertz A, Carroll P, Lambe M, Hammar N, Walldius G, Jungner I, Van Hemelrijck M: Serum glucose and fructosamine in relation to risk of cancer. PLoS One 2013, 8(1):e54944.
• [82]Cust AE, Kaaks R, Friedenreich C, Bonnet F, Laville M, Tjonneland A, Olsen A, Overvad K, Jakobsen MU, Chajes V, Clavel-Chapelon F, Boutron-Ruault MC, Linseisen J, Lukanova A, Boeing H, Pischon T, Trichopoulou A, Christina B, Trichopoulos D, Palli D, Berrino F, Panico S, Tumino R, Sacerdote C, Gram IT, Lund E, Quirós JR, Travier N, Martínez-García C, Larrañaga N, et al.: 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 2007, 14(3):755-767.
• [83]Limburg PJ, Stolzenberg-Solomon RZ, Vierkant RA, Roberts K, Sellers TA, Taylor PR, Virtamo J, Cerhan JR, Albanes D: Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers. Clin Gastroenterol Hepatol 2006, 4(12):1514-1521.
• [84]Stolzenberg-Solomon RZ, Graubard BI, Chari S, Limburg P, Taylor PR, Virtamo J, Albanes D: Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 2005, 294(22):2872-2878.
• [85]Yamada K, Araki S, Tamura M, Sakai I, Takahashi Y, Kashihara H, Kono S: Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. Int J Epidemiol 1998, 27(5):794-798.
• [86]Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, Dobs A, Savage PJ: Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 1999, 91(13):1147-1154.
• [87]Zhang Y, Liu Z, Yu X, Zhang X, Lu S, Chen X, Lu B: The association between metabolic abnormality and endometrial cancer: a large case–control study in China. Gynecol Oncol 2010, 117(1):41-46.
• [88]Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Li J, Ho GY, Xue X, Anderson GL, Kaplan RC, Harris TG, Howard BV, Wylie-Rosett J, Burk RD, Strickler HD: Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 2009, 101(1):48-60.
• [89]Sieri S, Muti P, Claudia A, Berrino F, Pala V, Grioni S, Abagnato CA, Blandino G, Contiero P, Schunemann HJ, Krogh V: Prospective study on the role of glucose metabolism in breast cancer occurrence. Int J Cancer 2012, 130(4):921-929.
• [90]Van Hemelrijck M, Garmo H, Hammar N, Jungner I, Walldius G, Lambe M, Holmberg L: The interplay between lipid profiles, glucose, BMI and risk of kidney cancer in the Swedish AMORIS study. Int J Cancer 2012, 130(9):2118-2128.
• [91]Van Hemelrijck M, Garmo H, Holmberg L, Walldius G, Jungner I, Hammar N, Lambe M: Prostate cancer risk in the Swedish AMORIS study: the interplay among triglycerides, total cholesterol, and glucose. Cancer 2011, 117(10):2086-2095.
• [92]Chao LT, Wu CF, Sung FY, Lin CL, Liu CJ, Huang CJ, Tsai KS, Yu MW: Insulin, glucose and hepatocellular carcinoma risk in male hepatitis B carriers: results from 17-year follow-up of a population-based cohort. Carcinogenesis 2011, 32(6):876-881.
• [93]Pollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008, 8(12):915-928.
• [94]Rose DP, Vona-Davis L: The cellular and molecular mechanisms by which insulin influences breast cancer risk and progression. Endocrine-related cancer 2012, 19(6):R225-R241.
• [95]Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M: Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005, 92(11):2076-2083.
• [96]Grundmark B, Garmo H, Loda M, Busch C, Holmberg L, Zethelius B: The metabolic syndrome and the risk of prostate cancer under competing risks of death from other causes. Cancer Epidemiol Biomarkers Prev 2010, 19(8):2088-2096.
• [97]Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M, Comparative Risk Assessment collaborating g: Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet 2005, 366(9499):1784-1793.