AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥ 6.5%, 48 mmol/mol] vs lowest [≤ 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. CONCLUSIONS/ INTERPRETATION: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.
AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥ 6.5%, 48 mmol/mol] vs lowest [≤ 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. CONCLUSIONS/ INTERPRETATION: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.
Authors: Jeanine M Genkinger; Donna Spiegelman; Kristin E Anderson; Leslie Bernstein; Piet A van den Brandt; Eugenia E Calle; Dallas R English; Aaron R Folsom; Jo L Freudenheim; Charles S Fuchs; Graham G Giles; Edward Giovannucci; Pamela L Horn-Ross; Susanna C Larsson; Michael Leitzmann; Satu Männistö; James R Marshall; Anthony B Miller; Alpa V Patel; Thomas E Rohan; Rachael Z Stolzenberg-Solomon; Bas A J Verhage; Jarmo Virtamo; Bradley J Willcox; Alicja Wolk; Regina G Ziegler; Stephanie A Smith-Warner Journal: Int J Cancer Date: 2011-03-04 Impact factor: 7.396
Authors: Sara Raimondi; Albert B Lowenfels; Antonio M Morselli-Labate; Patrick Maisonneuve; Raffaele Pezzilli Journal: Best Pract Res Clin Gastroenterol Date: 2010-06 Impact factor: 3.043
Authors: Joachim Spranger; Anja Kroke; Matthias Möhlig; Kurt Hoffmann; Manuela M Bergmann; Michael Ristow; Heiner Boeing; Andreas F H Pfeiffer Journal: Diabetes Date: 2003-03 Impact factor: 9.461
Authors: D Basso; M Plebani; P Fogar; G Del Favero; G Briani; T Meggiato; M P Panozzo; C Ferrara; F D'Angeli; A Burlina Journal: Pancreas Date: 1994-05 Impact factor: 3.327
Authors: Dominique S Michaud; Brian Wolpin; Ed Giovannucci; Simin Liu; Barbara Cochrane; JoAnn E Manson; Michael N Pollak; Jing Ma; Charles S Fuchs Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-09-28 Impact factor: 4.254
Authors: Alina Vrieling; H Bas Bueno-de-Mesquita; Hendriek C Boshuizen; Dominique S Michaud; Marianne T Severinsen; Kim Overvad; Anja Olsen; Anne Tjønneland; Françoise Clavel-Chapelon; Marie-Christine Boutron-Ruault; Rudolf Kaaks; Sabine Rohrmann; Heiner Boeing; Ute Nöthlings; Antonia Trichopoulou; Eftihia Moutsiou; Vardis Dilis; Domenico Palli; Vittorio Krogh; Salvatore Panico; Rosario Tumino; Paolo Vineis; Carla H van Gils; Petra H M Peeters; Eiliv Lund; Inger T Gram; Laudina Rodríguez; Antonio Agudo; Nerea Larrañaga; María-José Sánchez; Carmen Navarro; Aurelio Barricarte; Jonas Manjer; Björn Lindkvist; Malin Sund; Weimin Ye; Sheila Bingham; Kay-Tee Khaw; Andrew Roddam; Tim Key; Paolo Boffetta; Eric J Duell; Mazda Jenab; Valentina Gallo; Elio Riboli Journal: Int J Cancer Date: 2010-05-15 Impact factor: 7.396
Authors: Leticia M Nogueira; Christina C Newton; Michael Pollak; Debra T Silverman; Demetrius Albanes; Satu Männistö; Stephanie J Weinstein; Eric J Jacobs; Rachael Z Stolzenberg-Solomon Journal: Cancer Epidemiol Biomarkers Prev Date: 2017-01-17 Impact factor: 4.254
Authors: Shannon M Lynch; Jacqueline M Major; Richard Cawthon; Stephanie J Weinstein; Jarmo Virtamo; Qing Lan; Nathaniel Rothman; Demetrius Albanes; Rachael Z Stolzenberg-Solomon Journal: Int J Cancer Date: 2013-06-14 Impact factor: 7.396
Authors: Rachael Z Stolzenberg-Solomon; Catherine Schairer; Steve Moore; Albert Hollenbeck; Debra T Silverman Journal: Am J Clin Nutr Date: 2013-08-28 Impact factor: 7.045
Authors: Chen Yuan; Ying Bao; Chen Wu; Peter Kraft; Shuji Ogino; Kimmie Ng; Zhi Rong Qian; Douglas A Rubinson; Meir J Stampfer; Edward L Giovannucci; Brian M Wolpin Journal: J Clin Oncol Date: 2013-10-21 Impact factor: 44.544
Authors: Joanne W Elena; Emily Steplowski; Kai Yu; Patricia Hartge; Geoffrey S Tobias; Michelle J Brotzman; Stephen J Chanock; Rachael Z Stolzenberg-Solomon; Alan A Arslan; H Bas Bueno-de-Mesquita; Kathy Helzlsouer; Eric J Jacobs; Andrea LaCroix; Gloria Petersen; Wei Zheng; Demetrius Albanes; Naomi E Allen; Laufey Amundadottir; Ying Bao; Heiner Boeing; Marie-Christine Boutron-Ruault; Julie E Buring; J Michael Gaziano; Edward L Giovannucci; Eric J Duell; Göran Hallmans; Barbara V Howard; David J Hunter; Amy Hutchinson; Kevin B Jacobs; Charles Kooperberg; Peter Kraft; Julie B Mendelsohn; Dominique S Michaud; Domenico Palli; Lawrence S Phillips; Kim Overvad; Alpa V Patel; Leah Sansbury; Xiao-Ou Shu; Michael S Simon; Nadia Slimani; Dimitrios Trichopoulos; Kala Visvanathan; Jarmo Virtamo; Brian M Wolpin; Anne Zeleniuch-Jacquotte; Charles S Fuchs; Robert N Hoover; Myron Gross Journal: Cancer Causes Control Date: 2012-10-31 Impact factor: 2.506
Authors: Brian M Wolpin; Ying Bao; Zhi Rong Qian; Chen Wu; Peter Kraft; Shuji Ogino; Meir J Stampfer; Kaori Sato; Jing Ma; Julie E Buring; Howard D Sesso; I-Min Lee; John Michael Gaziano; Anne McTiernan; Lawrence S Phillips; Barbara B Cochrane; Michael N Pollak; JoAnn E Manson; Edward L Giovannucci; Charles S Fuchs Journal: J Natl Cancer Inst Date: 2013-07-11 Impact factor: 13.506