Probability of Pancreatic Cancer Following Diabetes: A Population-Based Study
2005; Elsevier BV; Volume: 129; Issue: 2 Linguagem: Inglês
10.1053/j.gastro.2005.05.007
ISSN1528-0012
AutoresSuresh T. Chari, Cynthia L. Leibson, Kari G. Rabe, Jeanine E. Ransom, Mariza de Andrade, Gloria M. Petersen,
Tópico(s)Pancreatitis Pathology and Treatment
ResumoBackground & Aims: Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. Methods: We assembled a population-based cohort of 2122 Rochester, Minnesota, residents age ≥50 years who first met standardized criteria for diabetes between January 1, 1950, and December 31, 1994, and identified those who developed pancreatic cancer within 3 years of meeting criteria for diabetes. We compared observed rates of pancreatic cancer with expected rates based on the Iowa Surveillance Epidemiology and End Results registry. In a nested case control study, we compared body mass index (BMI) and smoking status in diabetes subjects with and without pancreatic cancer. Results: Of 2122 diabetic subjects, 18 (0.85%) were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes; 10 of 18 (56%) were diagnosed <6 months after first meeting criteria for diabetes, and 3 were resected. The observed-to-expected ratio of pancreatic cancer in the cohort was 7.94 (95% CI, 4.70–12.55). Compared with subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61–12.74) years but did not differ significantly with respect to BMI values (29.2 ± 6.8 vs 26.5 ± 5.0, respectively). A larger proportion of those who developed pancreatic cancer were ever smokers (92% vs 69%, respectively), but this did not reach statistical significance. Conclusions: Approximately 1% of diabetes subjects aged ≥50 years will be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes. The usefulness of new-onset diabetes as marker of early pancreatic cancer needs further evaluation. Background & Aims: Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. Methods: We assembled a population-based cohort of 2122 Rochester, Minnesota, residents age ≥50 years who first met standardized criteria for diabetes between January 1, 1950, and December 31, 1994, and identified those who developed pancreatic cancer within 3 years of meeting criteria for diabetes. We compared observed rates of pancreatic cancer with expected rates based on the Iowa Surveillance Epidemiology and End Results registry. In a nested case control study, we compared body mass index (BMI) and smoking status in diabetes subjects with and without pancreatic cancer. Results: Of 2122 diabetic subjects, 18 (0.85%) were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes; 10 of 18 (56%) were diagnosed <6 months after first meeting criteria for diabetes, and 3 were resected. The observed-to-expected ratio of pancreatic cancer in the cohort was 7.94 (95% CI, 4.70–12.55). Compared with subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61–12.74) years but did not differ significantly with respect to BMI values (29.2 ± 6.8 vs 26.5 ± 5.0, respectively). A larger proportion of those who developed pancreatic cancer were ever smokers (92% vs 69%, respectively), but this did not reach statistical significance. Conclusions: Approximately 1% of diabetes subjects aged ≥50 years will be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes. The usefulness of new-onset diabetes as marker of early pancreatic cancer needs further evaluation. Pancreatic cancer patients seldom exhibit disease-specific symptoms until the cancer is at an advanced stage. If the tumor is to be discovered early, it will have to be done in asymptomatic individuals. A number of formidable obstacles limit the ability of health care providers to screen for pancreatic cancer. One of them is lack of a high-risk population for sporadic pancreatic cancer. Currently, rare genetic syndromes with a high incidence of pancreatic cancer are being targeted for screening using endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography.1Brentnall T.A. Bronner M.P. Byrd D.R. Haggitt R.C. Kimmey M.B. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer.Ann Intern Med. 1999; 131: 247-255Crossref PubMed Scopus (320) Google Scholar, 2Canto M. Wroblewski L. Goggins M. Petersen G. Brune K. Yea C. Giardello F. Hruban R. Screening for pancreatic neoplasia in high-risk individuals The Johns Hopkins Experience.Gastroenterology. 2002; 122: A-17Google Scholar, 3Goggins M. Canto M. Hruban R. Can we screen high-risk individuals to detect early pancreatic carcinoma?.J Surg Oncol. 2000; 74: 243-248Crossref PubMed Scopus (58) Google ScholarTo make headway in screening for sporadic pancreatic cancer, efforts to define populations at high risk for having or developing sporadic pancreatic cancer will have to develop pari passu with advances in imaging studies and identification of novel biomarkers. In this study, we highlight the potential for utilizing hyperglycemia and diabetes to define a population at high risk for having pancreatic cancer. We also discuss the limitations of this and other studies and provide insights into why we believe hyperglycemia and diabetes may be markers of “early” pancreatic cancer and what studies need to be done to prove this hypothesis.The association between diabetes and pancreatic cancer has long been recognized. However, the assessment of diabetes as a clinically relevant screening target for pancreatic cancer is complicated by the fact that, although long-standing diabetes is an etiologic factor for pancreatic cancer, new-onset diabetes is a manifestation of the cancer. Although most studies show an elevated risk of pancreatic cancer among persons with long-standing diabetes, the strength of this association is modest at best.4Everhart J. Wright D. Diabetes mellitus as a risk factor for pancreatic cancer a meta-analysis.JAMA. 1995; 273: 1605-1609Crossref PubMed Scopus (608) Google Scholar In a meta-analysis of 20 epidemiologic studies, the pooled relative risk of pancreatic cancer for those whose diabetes was diagnosed at least 1 year prior to either diagnosis of pancreatic cancer or to pancreatic cancer death was 2.1 (95% CI: 1.6–2.8).4Everhart J. Wright D. Diabetes mellitus as a risk factor for pancreatic cancer a meta-analysis.JAMA. 1995; 273: 1605-1609Crossref PubMed Scopus (608) Google Scholar Many, but not all, cohort studies reveal that the risk of pancreatic cancer associated with diabetes decreases with increasing duration of follow-up.5Ragozzino M. Melton L.J.D. Chu C.P. Palumbo P.J. Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus.J Chronic Dis. 1982; 35: 13-19Abstract Full Text PDF PubMed Scopus (216) Google Scholar, 6Wideroff L. Gridley G. Mellemkjaer L. Chow W.H. Linet M. Keehn S. Borch-Johnsen K. Olsen J.H. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark.J Natl Cancer Inst. 1997; 89: 1360-1365Crossref PubMed Scopus (565) Google Scholar, 7Calle E.E. Murphy T.K. Rodriguez C. Thun M.J. Heath Jr, C.W. Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults.Cancer Causes Control. 1998; 9: 403-410Crossref PubMed Scopus (127) Google Scholar, 8Adami H.O. McLaughlin J. Ekbom A. Berne C. Silverman D. Hacker D. Persson I. Cancer risk in patients with diabetes mellitus.Cancer Causes Control. 1991; 2: 307-314Crossref PubMed Scopus (299) Google Scholar, 9Chow W.H. Gridley G. Nyren O. Linet M.S. Ekbom A. Fraumeni Jr, J.F. Adami H.O. Risk of pancreatic cancer following diabetes mellitus a nationwide cohort study in Sweden.J Natl Cancer Inst. 1995; 87: 930-931Crossref PubMed Scopus (116) Google Scholar Additionally, although the number of persons with pancreatic cancer in the population is small, the number of older persons with long-standing diabetes is large. Thus long-standing diabetes as a marker for pancreatic cancer is likely to have limited clinical utility.There is increasing evidence to support the notion that diabetes may be a consequence of pancreatic cancer. Diabetes and hyperglycemia are present in up to 80% of pancreatic cancer,10Cersosimo E. Pisters P.W. Pesola G. McDermott K. Bajorunas D. et al.Insulin secretion and action in patients with pancreatic cancer.Cancer. 1991; 67: 486-493Crossref PubMed Scopus (104) Google Scholar, 11Permert J. Ihse I. Jorfeldt L. von Schenck H. Arnqvist H.J. Larsson J. Pancreatic cancer is associated with impaired glucose metabolism.Eur J Surg. 1993; 159: 101-107PubMed Google Scholar, 12Permert J. Larsson J. Ihse I. Pour P.M. Diagnosis of pancreatic cancer. Alteration of glucose metabolism.Int J Pancreatol. 1991; 9: 113-117PubMed Google Scholar, 13Chari S.T. Klee G.G. Miller L.J. Raimondo M. DiMagno E.P. Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer.Gastroenterology. 2001; 121: 640-645Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar are usually of recent onset,13Chari S.T. Klee G.G. Miller L.J. Raimondo M. DiMagno E.P. Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer.Gastroenterology. 2001; 121: 640-645Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 14Silverman D.T. Swanson C.A. Gridley G. Wacholder S. Greenberg R.S. Brown L.M. Hayes R.B. Swanson G.M. Schoenberg J.B. Pottern L.M. Schwartz A.G. Fraumeni Jr, J.F. Hoover R.N. Dietary and nutritional factors and pancreatic cancer a case control study based on direct interviews.J Natl Cancer Inst. 1998; 90: 1710-1719Crossref PubMed Scopus (233) Google Scholar, 15Jain M. Howe G.R. St Louis P. Miller A.B. Coffee and alcohol as determinants of risk of pancreas cancer a case control study from Toronto.Int J Cancer. 1991; 47: 384-389Crossref PubMed Scopus (105) Google Scholar, 16Gullo L. Pezzilli R. Morselli-Labate A.M. Italian Pancreatic Cancer Study GroupDiabetes and the risk of pancreatic cancer.N Engl J Med. 1994; 331: 81-84Crossref PubMed Scopus (298) Google Scholar, 17Moossa A.R. Levin B. Collaborative studies in the diagnosis of pancreatic cancer.Semin Oncol. 1979; 6: 298-308PubMed Google Scholar, 18Moossa A.R. Levin B. The diagnosis of “early” pancreatic cancer the University of Chicago experience.Cancer. 1968; 47: 1688-1697Crossref Scopus (111) Google Scholar, 19Bonelli L. Aste H. Bovo P. Cavallini G. Felder M. Gusmaroli R. Morandini E. Ravelli P. Briglia R. Lombardo L. De Micheli A. Pugliese V. Exocrine pancreatic cancer, cigarette smoking, and diabetes mellitus a case-control study in northern Italy.Pancreas. 2003; 27: 143-149Crossref PubMed Scopus (101) Google Scholar, 20Cuzick J. Babiker A.G. Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease.Int J Cancer. 1989; 43: 415-421Crossref PubMed Scopus (190) Google Scholar, 21Permert J. Ihse I. Jorfeldt L. von Schenck H. Arnquist H.J. Larsson J. Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer.Br J Surg. 1993; 80: 1047-1050Crossref PubMed Scopus (205) Google Scholar and improve or remit after resection of cancer.21Permert J. Ihse I. Jorfeldt L. von Schenck H. Arnquist H.J. Larsson J. Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer.Br J Surg. 1993; 80: 1047-1050Crossref PubMed Scopus (205) Google Scholar Based on such observations, new-onset diabetes has been suggested as a possible target for screening for pancreatic cancer.11Permert J. Ihse I. Jorfeldt L. von Schenck H. Arnqvist H.J. Larsson J. Pancreatic cancer is associated with impaired glucose metabolism.Eur J Surg. 1993; 159: 101-107PubMed Google Scholar, 15Jain M. Howe G.R. St Louis P. Miller A.B. Coffee and alcohol as determinants of risk of pancreas cancer a case control study from Toronto.Int J Cancer. 1991; 47: 384-389Crossref PubMed Scopus (105) Google Scholar, 16Gullo L. Pezzilli R. Morselli-Labate A.M. Italian Pancreatic Cancer Study GroupDiabetes and the risk of pancreatic cancer.N Engl J Med. 1994; 331: 81-84Crossref PubMed Scopus (298) Google Scholar, 17Moossa A.R. Levin B. Collaborative studies in the diagnosis of pancreatic cancer.Semin Oncol. 1979; 6: 298-308PubMed Google Scholar, 22Noy A. Bilezikian J.P. Clinical review 63: diabetes and pancreatic cancer: clues to the early diagnosis of pancreatic malignancy.J Clin Endocrinol Metab. 1994; 79: 1223-1231Crossref PubMed Scopus (53) Google Scholar However, it is important to recognize that previous epidemiologic studies of the association between diabetes and pancreatic cancer are generally uninformative about the clinical utility of newly identified diabetes as a marker for pancreatic cancer. In almost all case control studies, duration of diabetes is unclear because it was assessed by self- or proxy report. Three studies have used postload glucose levels at baseline, and persons with and without prevalent diabetes have been followed forward for pancreatic cancer.23Levine W. Dyer A.R. Shekelle R.B. Schoenberger J.A. Stamler J. Post-load plasma glucose and cancer mortality in middle-aged men and women. 12-year follow-up findings of the Chicago Heart Association Detection Project in Industry.Am J Epidemiol. 1990; 131: 254-262Crossref PubMed Scopus (93) Google Scholar, 24Gapstur S.M. Gann P.H. Lowe W. Liu K. Colangelo L. Dyer A. Abnormal glucose metabolism and pancreatic cancer mortality.JAMA. 2000; 283: 2552-2558Crossref PubMed Scopus (343) Google Scholar, 25Smith G.D. Egger M. Shipley M.J. Marmot M.G. Post-challenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men.Am J Epidemiol. 1992; 136: 1110-1114PubMed Google Scholar However, these studies are relatively uninformative regarding the short-term risk of pancreatic cancer associated with diabetes because the mean age was relatively young,23Levine W. Dyer A.R. Shekelle R.B. Schoenberger J.A. Stamler J. Post-load plasma glucose and cancer mortality in middle-aged men and women. 12-year follow-up findings of the Chicago Heart Association Detection Project in Industry.Am J Epidemiol. 1990; 131: 254-262Crossref PubMed Scopus (93) Google Scholar, 24Gapstur S.M. Gann P.H. Lowe W. Liu K. Colangelo L. Dyer A. Abnormal glucose metabolism and pancreatic cancer mortality.JAMA. 2000; 283: 2552-2558Crossref PubMed Scopus (343) Google Scholar and there were very few pancreatic cancer deaths within the first 5 years among persons with diabetes at baseline.23Levine W. Dyer A.R. Shekelle R.B. Schoenberger J.A. Stamler J. Post-load plasma glucose and cancer mortality in middle-aged men and women. 12-year follow-up findings of the Chicago Heart Association Detection Project in Industry.Am J Epidemiol. 1990; 131: 254-262Crossref PubMed Scopus (93) Google Scholar, 24Gapstur S.M. Gann P.H. Lowe W. Liu K. Colangelo L. Dyer A. Abnormal glucose metabolism and pancreatic cancer mortality.JAMA. 2000; 283: 2552-2558Crossref PubMed Scopus (343) Google ScholarTo assess the potential benefit of screening for pancreatic cancer among subjects with newly identified diabetes, population-based cohort studies are needed. In previous studies, estimates of the prevalence of newly diagnosed diabetes among controls do not afford estimates of the prevalence of newly diagnosed diabetes in the population. This limitation also applies to cohort studies in which the study population is limited to persons with prevalent diabetes who are not necessarily representative of persons with diabetes in the population generally (ie, hospitalized diabetes cases or patients of a diabetes clinic). Thus, there is a need for studies that afford estimates of both the number of newly diagnosed cases of diabetes that exist within the population and of the excess risk of pancreatic cancer associated specifically with newly identified diabetes.Our study used the longitudinal, population-based resources of the Rochester Epidemiology Project (REP)26Melton III, L.J. History of the Rochester Epidemiology Project.Mayo Clin Proc. 1996; 71: 266-274Abstract Full Text Full Text PDF PubMed Scopus (1338) Google Scholar to identify all Rochester, Minnesota, residents who first met standardized research criteria for diabetes on or after age 50 years between January 1, 1950, and December 31, 1994. In this cohort, we determined the likelihood of pancreatic cancer diagnosis within 3 years of meeting criteria for diabetes and compared observed rates with those expected for persons of similar age and sex distribution. Among persons with diabetes, we compared those with and without pancreatic cancer for other known or potential risk factors, ie, age, sex, smoking, and body mass index (BMI).Patients and MethodsThe study was approved by the Mayo Foundation Institutional Review Board (IRB). Population-based studies are possible in Rochester, Minnesota, because essentially all medical care received by local residents is delivered by the Mayo Clinic and the Olmsted Medical Center. Since 1907, every Mayo Clinic patient has been assigned a unique identifier. All information from every contact (including hospital inpatient or outpatient care, office visits, emergency room, and nursing home care, as well as death certificate and autopsy information) is contained within a single dossier for each patient, and diagnoses assigned at each visit are entered into computer files. Under the auspices of the Rochester Epidemiology Project (REP), this diagnostic index and medical records linkage were expanded to include the other providers of care to local residents,26Melton III, L.J. History of the Rochester Epidemiology Project.Mayo Clin Proc. 1996; 71: 266-274Abstract Full Text Full Text PDF PubMed Scopus (1338) Google Scholar thus providing a comprehensive medical database of the Rochester population.Rochester Diabetes Incidence CohortREP resources were used to construct the Rochester diabetes incidence cohort.27Burke J.P. O’Brien P. Ransom J. Palumbo P.J. Lydick E. Yawn B.P. Joseph Melton III, L. Leibson C.L. Impact of case ascertainment on recent trends in diabetes incidence in Rochester, Minnesota.Am J Epidemiol. 2002; 155: 859-865Crossref PubMed Scopus (24) Google Scholar, 28Leibson C.L. Williamson D.F. Melton III, L.J. Palumbo P.J. Smith S.A. Ransom J.E. Schilling P.L. Narayan K.M. Temporal trends in BMI among adults with diabetes.Diabetes Care. 2001; 24: 1584-1589Crossref PubMed Scopus (102) Google Scholar, 29Thomas R.J. Palumbo P.J. Melton III, L.J. Roger V.L. Ransom J. O’Brien P.C. Leibson C.L. Trends in the mortality burden associated with diabetes mellitus a population-based study in Rochester, Minn, 1970–1994.Arch Intern Med. 2003; 163: 445-451Crossref PubMed Scopus (85) Google Scholar The full cohort includes all 2151 individuals who first met research criteria for diabetes as a Rochester resident between 1950 and 1995. In constructing this cohort, confirmation of diabetes status was based on review of provider-linked medical records by trained nurse abstractors, under the direction of an endocrinologist. Records were reviewed from date of first contact with each REP provider until date of last contact, death, or end of the study period for all laboratory glucose values and evidence of any antidiabetic medication. Laboratory glucose values are available within REP medical records for 1930 through the present. Glycemic criteria approximated National Diabetes Data Group (NDDG) recommendations,30National Diabetes Data GroupClassification and diagnosis of diabetes mellitus and other categories of glucose intolerance.Diabetes Care. 1979; 28: 1039-1057Crossref Scopus (5477) Google Scholar ie, 2 consecutive fasting glucose levels ≥140 mg/dL (7.8 mmol/L) or both 1- and 2-hour levels ≥200 mg/dL (11.1 mmol/L) obtained during a standard oral glucose tolerance test. Adjustments were made for changes in laboratory methods over time.31West K. Standardization of definition, classification, and reporting in diabetes-related epidemiologic studies.Diabetes Care. 1979; 2: 65-76Crossref PubMed Scopus (24) Google Scholar Individuals who failed to meet glycemic criteria but who used oral agents or insulin for at least 2 weeks or until death also qualified as cases.Because it was not feasible to review manually all medical records for every Rochester resident over this 45-year period, the review was limited to candidate cases, ie, all residents with any diagnosis suggestive of diabetes (eg, elevated blood glucose, impaired glucose tolerance, diabetes mellitus, rule-out diabetes, diabetic nephropathy) in the REP diagnostic index. In a previous study of all Rochester residents who died on or after age 45 years in 1970–1995, the median number of years of medical records available for review (ie, time from first contact with a REP provider until death) was 43 years (interquartile range, 24–58 years), and over 25% of all decedents had a diagnosis in the REP diagnostic index that qualified them as a candidate case for the diabetes incidence cohort.29Thomas R.J. Palumbo P.J. Melton III, L.J. Roger V.L. Ransom J. O’Brien P.C. Leibson C.L. Trends in the mortality burden associated with diabetes mellitus a population-based study in Rochester, Minn, 1970–1994.Arch Intern Med. 2003; 163: 445-451Crossref PubMed Scopus (85) Google Scholar It has also been demonstrated that essentially all Rochester residents have contact with at least 1 REP provider in any 5-year period.26Melton III, L.J. History of the Rochester Epidemiology Project.Mayo Clin Proc. 1996; 71: 266-274Abstract Full Text Full Text PDF PubMed Scopus (1338) Google Scholar In each year, the proportion of local residents age ≥30 years who have at least 1 blood glucose measurement averages approximately 37% for males and 44% for females.27Burke J.P. O’Brien P. Ransom J. Palumbo P.J. Lydick E. Yawn B.P. Joseph Melton III, L. Leibson C.L. Impact of case ascertainment on recent trends in diabetes incidence in Rochester, Minnesota.Am J Epidemiol. 2002; 155: 859-865Crossref PubMed Scopus (24) Google ScholarThe present study was limited to individuals who first met criteria for diabetes between January 1, 1950, and December 31, 1994, on or after age 50 years and who were residing in Rochester for at least 1 year as of the date they first met criteria (ie, incident cases) (Figure 1). In accordance with a Minnesota statute,32Melton III, L.J. The threat to medical-records research.N Engl J Med. 1997; 337: 1466-1470Crossref PubMed Scopus (198) Google Scholar 24 individuals who declined to authorize the use of their medical records in the research were excluded from the study. Thus, there were 2127 authorized and eligible incident diabetes cases (Figure 1).Ascertainment of Incident Pancreatic CancersThe list of 2127 incident diabetes cases was cross matched with the diagnostic index maintained by the REP to identify those with any diagnosis of pancreatic adenocarcinoma within 3 years of meeting criteria for diabetes (n = 27). After review of the medical records of these 27 subjects, 9 were excluded (5 who were found to have developed diabetes after pancreatectomy or cancer and 4 who were found to not have pancreatic ductal adenocarcinoma) (Figure 1).Selection of Controls for Nested Case Control StudyFor each of the 18 remaining diabetes cases who met criteria for pancreatic ductal adenocarcinoma, 4 members of the diabetes cohort were identified who were of same sex, similar year of birth, and similar year in which criteria for diabetes were met, but for whom there was no diagnosis of pancreatic cancer.Statistical AnalysesIncidence and risk of pancreatic cancer in the diabetes cohortThe incidence of pancreatic cancer among members of the cohort was calculated as the ratio of observed cases to the number of diabetes person-years of follow-up. Diabetes person-years were calculated from the date that all 2122 members of the diabetes cohort first met criteria for diabetes, until the earliest of pancreatic cancer diagnosis, death, or 3 years.The excess risk of pancreatic cancer within 3 years of first meeting criteria for diabetes mellitus was estimated by comparing the observed number of cases among members of the diabetes incidence cohort to the expected number of cases in the general population. The expected number was estimated by multiplying the number of diabetes person-years for each 5-year age group and sex by the corresponding age- and sex-specific incidence rates from data from the Surveillance, Epidemiology, and End Results (SEER) program.33National Cancer Institute. Surveillance and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence-SEER 9 Regs Public-Use, Nov 2002 Sub (1973–2000) , National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2003, based on the November 2002 submission.Google Scholar The incidence of pancreatic cancer in Olmsted county has been reported.34Riela A. Zinsmeister A.R. Melton III, L.J. Weiland L.H. DiMagno E.P. Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988.Mayo Clin Proc. 1992; 67: 839-845Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar The study by Riela et al34Riela A. Zinsmeister A.R. Melton III, L.J. Weiland L.H. DiMagno E.P. Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988.Mayo Clin Proc. 1992; 67: 839-845Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar showed that the incidence of pancreatic cancer in Olmsted county is very similar to the incidence of pancreatic cancer in the Iowa SEER population. However, the study by Riela et al34Riela A. Zinsmeister A.R. Melton III, L.J. Weiland L.H. DiMagno E.P. Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988.Mayo Clin Proc. 1992; 67: 839-845Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar did not cover the entire period of our study, and the number of patients diagnosed with pancreatic cancer each year is small. We therefore chose to use the Iowa SEER data because Iowa is the nearest state with SEER data available in the United States, and the demographics of Iowa are very similar to those of Rochester, Minnesota.Risk ratios (defined as the ratio of observed to expected number of cases of pancreatic cancer) and 95% confidence intervals (based on the Poisson distribution of the observed number of pancreatic cancer cases) were estimated, both overall and for subgroups (ie, ages <70 vs ≥70 years; male vs female).35Bergstalh EJ, Offord KP, Kosanke JL, Augustine GA. PERSONYEARS: a SAS procedure for person year analyses: Rochester, MN: Section of Medical Research Statistics, Mayo Clinic; April 1986. Technical Report Series, No.31.Google ScholarNested case control studyTo evaluate whether there was an association between smoking or BMI and pancreatic cancer among persons with diabetes, the analysis included the 4 diabetes controls for each case, for a total of 72 controls and 18 cases.36Breslow N.E. Day N.E. Statistical methods in cancer research. IARC Workshop. IARC Scientific Publications. Volume No. 82. IARC, Lyon, France1987Google Scholar The medical records of these 90 individuals were reviewed for smoking history, classified as ever, never, or unknown. BMI (weight in kilograms/height in meters2) as of the date criteria for diabetes were met (±2 years) was noted. To obtain risk ratios and 95% confidence intervals, we employed conditional logistic regression, matching on age and sex. Statistical analyses were conducted using Statistical Analysis Software (SAS) version 8 (SAS Institute, Cary, NC).ResultsBetween January 1, 1950, and December 31, 1994, there were 2122 Rochester residents ≥50 years of age who first met National Diabetes Data Group (NDDG) criteria for diabetes (male, 50%; mean age, 66.2 ± 10.1 years). Persons were followed to the earliest of pancreatic cancer diagnosis, death, or 3 years, for a total of 5799 person-years of follow-up in the diabetes cohort; during which time, 18 subjects (0.85%) met criteria for pancreatic cancer.Characteristics of Diabetes Associated With Pancreatic CancerThere was no family history of diabetes in 11 of 18 (61%) subjects; 3 had siblings with diabetes and 1 each had a parent and uncle with diabetes. Data on family history were not available in 2 patients. Seven (39%) subjects were treated with insulin and 3 with oral hypoglycemics; the remaining subjects were not on hypoglycemic medications. At the time patients met criteria for diabetes, 9 of 18 had cancer-related symptoms, 2 had diabetes-related symptoms (polydipsia and polyphagia), and the remaining had no symptoms or were being investigated for an unrelated problem (eg, atrial fibrillation).Characteristics of Pancreatic Cancer Associated With DiabetesTwelve of 18 (67%) subjects were males (Table 1). Their mean age at cancer diagnosis was 72.3 ± 8.1 years. On average, pancreatic cancer was identified 6.6 ± 7.7 months after the date diabetes criteria were met. In 10 of 18 (56%), the cancer was diagnosed <6 months after first meeting criteria for diabetes. The cancer was resected in 3 and was unresectable in the remaining patients.Table 1Characteristics of the 18 Subjects With Pancreatic Cancer in the Rochester Diabetes Incidence CohortPatient No.Age (y)aAge at diagnosis of pancreatic cancer.SexInterval (mo)bInterval between date criteria for diabetes met and date of diagnosis of pancreas cancer.Procedure to diagnose pancreatic cancerBMI as of date diabetes criteria metSmoking166M<1Laparotomy with biopsy26.8Ever262F<1Distal pancreatectomy27.5Ever374M<1Autopsy24.1Unknown480F<1Laparotomy, biliary bypass35.6Ever589M<1Laparotomy with biopsy21.2Unknown670F<1Pancreatico-duodenect
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