Abstract
Purposes
Our study aimed to examine the impact of diabetes, smoking and BMI on pancreatic cancer survival in a population-based setting by adjusting both sociodemographic and clinical factors and measuring their attributable risk.
Methods
Data on pancreatic adenocarcinoma patients diagnosed in 2011–2017 were acquired from the Louisiana Tumor Registry. Diabetes, smoking, height, and weight were abstracted from medical records and linked with Hospital Inpatient Discharge Data to enhance the completeness of the diabetes data. The Cox regression model was used to assess effect sizes of diabetes, smoking, and BMI on cancer-specific survival and survival rate. The partial population attributable risk was employed to measure the attributable risk of these risk factors.
Results
Of the 3,200 eligible patients, 34.6% were diabetics, 23.9% were current smokers, and 52.3% had BMI ≥ 25 kg/m2. After adjusting for sociodemographic and clinical factors, diabetic patients had an increased cancer-specific death risk of 15% (95% CI, 1.06–1.25), 36% (95% CI, 1.19–1.44) for current smokers, and 24% (95% CI, 1.00–1.54) for patients with a BMI ≥ 40 when compared to their counterparts. Diabetic current smokers had significantly lower 2- and 3-year adjusted cancer-specific survival rates, 13.1% and 10.5%, respectively. By eliminating diabetes and modifiable risk factors, an estimated 16.6% (95% CI, 6.9%–25.9%) of the cancer-specific deaths could be avoided during a nine-year observational period between 2011 and 2019.
Conclusions
Diabetes and smoking contributed substantially to the reduction of pancreatic cancer survival even after controlling for sociodemographic and clinical factors; however, BMI ≥ 35 was observed to increase risk of mortality among stage III–IV patients only.
Similar content being viewed by others
Data availability
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
References
Siegel RL, Miller KD, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71:7–33
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74(11):2913–2921
Gullo L, Pezzilli R, Morselli-Labate M, Italian Pancreatic Cancer Study Group (1994) Diabetes and the risk of pancreatic cancer. New Eng J Med 331(2):81–84
Everhart J, Wright D (1995) Diabetes Mellitus as a risk factor for pancreatic cancer-A meta-analysis. JAMA 273(20):1605–1609
Wang F, Gupta A, Holly EA (2006) Diabetes mellitus and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California. Cancer Epidemiol Biomarkers Prev 15(8):1458–1463
Gupta S, Vittinghoff E, Bertenthal D, Corley D, Shen H, Walter LC, McQuaid K (2006) New-onset diabetes and pancreatic cancer. Clin Gastroenterol Hepatol 4:1366–1372
Chari ST, Leibson CL, Rabe KG, Timmons LJ, Ransom J, de Andrade M, Petersen GM (2008) Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 134:95–101
Setiawan VW, Stram DO, Porcel J, Chari ST, Maskarinec G, Marchand LL, Wilkens LR, Haiman CA, Pandol SJ, Monroe KR (2019) Pancreatic cancer following incident diabetes in African Americans and Latinos: The Multiethnic Cohort. J Natl Cancer Inst 111(1):27–33
Calle EE, Murphy TK, Rodriguez C, Thun MJ, Heath CW (1998) Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control 9(4):403–410
Toriola AT, Stolzenberg-Solomon R, Dalidowitz L (2014) Diabetes and pancreatic cancer survival: a prospective cohort-based study. Br J Cancer 111:181–185
Kleeff J, Costello E, Jackson R et al (2016) The impact of diabetes mellitus on survival following resection and adjuvant chemotherapy for pancreatic cancer. Br J Cancer 115:887–894
Silverman DT, Dunn JA, Hoover RN, Schiffman M, Lillemoe KD, Schoenberg JB, Brown LM, Greenberg RS, Hayes RB, Swanson GM et al (1994) Cigarette smoking and pancreas cancer: a case-control study based on direct interviews. J Natl Cancer Inst 86(20):1510–1516
Bosetti C, Lucenteforte E, Silverman DT et al (2012) Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 23:1880–1888
Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS (2001) Physical activity, obesity height and the risk of pancreatic cancer. JAMA 286:921–929
Yuan C, Morales-Oyarvide V, Babic A et al (2017) Cigarette Smoking and Pancreatic Cancer Survival. J Clin Oncol 35(16):1822–1828
Ansary-Moghaddam A, Huxley R, Barzi F, Lawes C, Ohkubo T, Fang X, Jee SH, Woodward M, Collaboration APCS (2006) The effect of modifiable risk factors on pancreatic cancer mortality in populations of the Asia-Pacific Region. Cancer Epidemiol Biomarkers Prev 15:2435–2440
McWilliams RR, Matsumoto ME, Burch PA, Kim GP, Thorvardur R, Halfdanarson TR, De Andrade M, Reid-Lombardo K, Bamlet WR (2010) Obesity adversely affects survival in pancreatic cancer patients. Cancer 116(21):5054–5062
Yuan C, Bao Y, Wu C, Kraft P, Ogino S, Ng K, Qian ZR, Rubinson DA, Stampfer MJ, Giovannucci EL, Wolpin BM (2013) Prediagnostic body mass index and pancreatic cancer survival. J Clin Oncol 31:4229–4234
Pelucchi C, Galeone C, Polesel J et al (2014) Smoking and body mass index and survival in pancreatic cancer patients. Pancreas 43:47–52
America's Health Rankings analysis of CDC, Behavioral Risk Factor Surveillance System, United Health Foundation, AmericasHealthRankings.org. https://www.americashealthrankings.org/. Accessed February 2, 2021.
Chen VW, Eheman CR, Johnson CJ, Hernandez MN, Rousseau D, Styles TS, West DW, Hsieh MC, Hakenewerth AM, Celaya MO, Rycroft RK, Wike JM, Pearson M, Brockhouse J, Mulvihill LG, Zhang KB (2014) Enhancing cancer registry data for comparative effectiveness research (CER) project: overview and methodology. J Regist Manag 41(3):103–112
SEER Cause-specific Death Classification. http://seer.cance r.gov/cause speci fic/index .html. Accessed July 10, 2020
Zhang X, Loberiza FR, Klein JP, Zhang M-J (2007) A SAS macro for estimation of direct adjusted survival curves based on a stratified Cox regression model. Comput Methods Programs Biomed 88:95–101
Spiegelman D, Hertzmark E, Wand HC (2007) Point and interval estimates of partial population attributable risks in cohort studies: examples and software. Cancer Causes Control 18:571–579. https://doi.org/10.1007/s10552-006-0090-y
Hertzmark E, Wand H, Spiegelman D (2012). The SAS PAR Macro https://cdn1.sph.harvard.edu/wp-content/uploads/sites/271/2012/09/par_documentation-_march_2012.pdf
Gong Z, Holly EA, Bracci PM (2012) Obesity and survival in population-based patients with pancreatic cancer in the San Francisco Bay Area. Cancer Causes Control 23:1929–1937
Hwang A, Narayan V, Yang YX (2013) Type 2 diabetes mellitus and survival in pancreatic adenocarcinoma: a retrospective cohort study. Cancer 119(2):404–410
Yuan C, Rubinson CA, Qian ZR et al (2015) Survival among patients with pancreatic cancer and long-standing or recent-onset diabetes mellitus. J Clin Oncol 33:29–35
Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A (2000) Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 283:2552–2558
Rozengurt E, Sinnett-Smith J, Kisfalvi K (2010) Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer. Clin Cancer Res 16:2505–2511
Regel I, Kong B, Raulefs S, Erkan M, Michalski CW, Hartel M, Kleeff J (2012) Energy metabolism and proliferation in pancreatic carcinogenesis. Langenbeck’s Arch Surg 397(4):507–512
Trevino JG, Pillai S, Kunigal S, Singh S, Fulp WJ, Chellappan CBA, SP, (2012) Nicotine induces inhibitor of differentiation-1 in a Src-dependent pathway promoting metastasis and chemo resistance in pancreatic adenocarcinoma. Neoplasia 14:1102–1114
Delitto D, Zhang D, Han S et al (2016) Nicotine reduces survival via augmentation of paracrine HGF-MET signaling in the pancreatic cancer microenvironment. Clin Cancer Res 22:1787–1799
Kasenda B, Bass A, Koeberle D, Pestalozzi B, Borner M, Herrmann R, Jost L, Lohri A, Hess V (2014) Survival in overweight patients with advanced pancreatic carcinoma: a multicentre cohort study. BMC Cancer 14:728
Parekh N, Chandran U, Bandera EV, EV, (2012) Obesity and cancer survival. Annu Rev Nutr 32:311–342. https://doi.org/10.1146/annurev-nutr-071811-150713
Griggs JJ, Sorbero ME, Lyman GH (2005) Undertreatment of obese women receiving breast cancer chemotherapy. Arch Intern Med 165:1267–1273
Gapstur SM, Jacobs EJ, Deka A, McCullough ML, Patel AV, Thun MJ (2011) Association of alcohol intake with pancreatic cancer mortality in never smokers. Arch Intern Med 171(5):444–451
Zhang S, Wang C, Huang H et al (2017) Effects of alcohol drinking and smoking on pancreatic ductal adenocarcinoma mortality: A retrospective cohort study consisting of 1783 patients. Scienific Reports 7:9572. https://doi.org/10.1038/s41598-017-08794-1
Acknowledgments
This work was supported in part by Louisiana State University Health Sciences Center, the Centers for Disease Control and Prevention under cooperative agreement of the National Program of Cancer Registries Grant Number NU58DP006332, and the National Cancer Institute’s Contract Number HHSN2612018000071.
Author information
Authors and Affiliations
Contributions
M-CH and LZ devised the project and the main conceptual ideas and performed literature review. M-CH and CV-G conducted statistical plan, analyzed the data, and verified the analytical methods. YY performed data inquiry and data linkage. LP performed data collection and quality assessment. M-CH the lead in writing the initial manuscript. X-CW, VC, and ET provided specifically critical review, commentary, and revision. All authors contributed to review and edit the final version of manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no potential conflicts of interest.
Ethical approval
We received institutional review board (IRB) approval from the Louisiana State University Health Sciences Center—New Orleans to use Louisiana Tumor Registry data for this study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hsieh, MC., Zhang, L., Velasco-Gonzalez, C. et al. Impact of diabetes and modifiable risk factors on pancreatic cancer survival in a population-based study after adjusting for clinical factors. Cancer Causes Control 33, 37–48 (2022). https://doi.org/10.1007/s10552-021-01497-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-021-01497-z