Abstract
Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
Data Availability
Information to submit an application to have access to EPIC data and/or biospecimens can be found at http://epic.iarc.fr/access/index.ph.
Abbreviations
- BMI:
-
Body Mass Index
- CI:
-
Confidence interval
- EPIC:
-
European Prospective Investigation into Cancer and Nutrition
- HR:
-
Hazard ratio
- PC:
-
Pancreatic cancer
- PAF:
-
Population attributable fraction
- WHR:
-
Waist-to-hip ratio
References
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.
Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2014. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2014;25:1650–6.
Ferlay J, Partensky C, Bray F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. Acta Oncol Stockh Swed. 2016;55:1158–60.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
Lindquist CM, Miller FH, Hammond NA, Nikolaidis P. Pancreatic cancer screening. Abdom Radiol N Y. 2018;43:264–72.
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum World Health Organ Int Agency Res Cancer. 2012;100:1–538.
Maisonneuve P, Lowenfels AB. Risk factors for pancreatic cancer: a summary review of meta-analytical studies. Int J Epidemiol. 2015;44:186–98.
World Cancer Research Fund/American Institute for Cancer Research. Continuous update project expert report. Diet, nutrition, physical activity and pancreatic cancer. 2018. www.dietandcancerreport.org.
Jiao L, Mitrou PN, Reedy J, Graubard BI, Hollenbeck AR, Schatzkin A, et al. A combined healthy lifestyle score and risk of pancreatic cancer in a large cohort study. Arch Intern Med. 2009;169:764–70.
Lucas AL, Bravi F, Boffetta P, Polesel J, Serraino D, La Vecchia C, et al. Adherence to World Cancer Research Fund/American Institute for Cancer Research recommendations and pancreatic cancer risk. Cancer Epidemiol. 2016;40:15–21.
Schuit AJ, van Loon AJM, Tijhuis M, Ocké M. Clustering of lifestyle risk factors in a general adult population. Prev Med. 2002;35:219–24.
Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med. 2000;343:16–22.
Kurth T, Moore SC, Gaziano JM, Kase CS, Stampfer MJ, Berger K, et al. Healthy lifestyle and the risk of stroke in women. Arch Intern Med. 2006;166:1403–9.
Catsburg C, Miller AB, Rohan TE. Adherence to cancer prevention guidelines and risk of breast cancer. Int J Cancer. 2014;135:2444–52.
Arthur R, Kirsh VA, Kreiger N, Rohan T. A Healthy Lifestyle Index and its association with risk of breast, endometrial, and ovarian cancer among Canadian women. Cancer Causes Control. 2018;29:485–93.
Inoue-Choi M, Robien K, Lazovich D. Adherence to the WCRF/AICR guidelines for cancer prevention is associated with lower mortality among older female cancer survivors. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2013;22:792–802.
McCullough ML, Patel AV, Kushi LH, Patel R, Willett WC, Doyle C, et al. Following cancer prevention guidelines reduces risk of cancer, cardiovascular disease, and all-cause mortality. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2011;20:1089–97.
Aleksandrova K, Pischon T, Jenab M, Bueno-de-Mesquita HB, Fedirko V, Norat T, et al. Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study. BMC Med. 2014;12:168.
McKenzie F, Ferrari P, Freisling H, Chajès V, Rinaldi S, de Batlle J, et al. Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition Cohort Study. Int J Cancer. 2015;136:2640–8.
Buckland G, Travier N, Huerta JM, Bueno-de-Mesquita HB, Siersema PD, Skeie G, et al. Healthy Lifestyle Index and risk of gastric adenocarcinoma in the EPIC cohort study. Int J Cancer. 2015;137:598–606.
McKenzie F, Biessy C, Ferrari P, Freisling H, Rinaldi S, Chajès V, et al. Healthy lifestyle and risk of cancer in the European Prospective Investigation Into Cancer and Nutrition Cohort Study. Medicine (Baltimore). 2016;95:e2850.
Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, et al. European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr. 2002;5:1113–24.
Kaaks R, Slimani N, Riboli E. Pilot phase studies on the accuracy of dietary intake measurements in the EPIC project: overall evaluation of results. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol. 1997;26(Suppl 1):S26–36.
Spencer EA, Appleby PN, Davey GK, Key TJ. Validity of self-reported height and weight in 4808 EPIC-Oxford participants. Public Health Nutr. 2002;5:561–5.
Spencer EA, Roddam AW, Key TJ. Accuracy of self-reported waist and hip measurements in 4492 EPIC-Oxford participants. Public Health Nutr. 2004;7:723–7.
Chajès V, Biessy C, Byrnes G, Deharveng G, Saadatian-Elahi M, Jenab M, et al. Ecological-level associations between highly processed food intakes and plasma phospholipid elaidic acid concentrations: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Nutr Cancer. 2011;63:1235–50.
Saadatian-Elahi M, Slimani N, Chajès V, Jenab M, Goudable J, Biessy C, et al. Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2009;89:331–46.
Willett WC, Howe GR, Kushi LH. Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr. 1997;65:1220S–1228S; discussion 1229S–1231S.
Berrington de González A, Spencer EA, Bueno-de-Mesquita HB, Roddam A, Stolzenberg-Solomon R, Halkjaer J, et al. Anthropometry, physical activity, and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2006;15:879–85.
Janssen I, Heymsfield SB, Allison DB, Kotler DP, Ross R. Body mass index and waist circumference independently contribute to the prediction of nonabdominal, abdominal subcutaneous, and visceral fat. Am J Clin Nutr. 2002;75:683–8.
Ferrari P, Day NE, Boshuizen HC, Roddam A, Hoffmann K, Thiébaut A, et al. The evaluation of the diet/disease relation in the EPIC study: considerations for the calibration and the disease models. Int J Epidemiol. 2008;37:368–78.
Thiébaut ACM, Bénichou J. Choice of time-scale in Cox’s model analysis of epidemiologic cohort data: a simulation study. Stat Med. 2004;23:3803–20.
Ferrari P, Jenab M, Norat T, Moskal A, Slimani N, Olsen A, et al. Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer. 2007;121:2065–72.
Ferrari P, Licaj I, Muller DC, Kragh Andersen P, Johansson M, Boeing H, et al. Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. BMJ Open. 2014;4:e005245.
Naudin S, Li K, Jaouen T, Assi N, Kyrø C, Tjønneland A, et al. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study. Int J Cancer. 2018;143:801–12.
Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika. 1982;69:239–41.
Barendregt JJ, Veerman JL. Categorical versus continuous risk factors and the calculation of potential impact fractions. J Epidemiol Community Health. 2010;64:209–12.
Efron B, Tibshirani R. Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci. 1986;1:54–75.
Lambert PC, Royston P. Further development of flexible parametric models for survival analysis. Stata J. 2009;9(2):21.
StataCorp. Stata statistical software: release 14. College Station: StataCorp LP; 2015.
Krebs-Smith SM, Pannucci TE, Subar AF, Kirkpatrick SI, Lerman JL, Tooze JA, et al. Update of the Healthy Eating Index: HEI-2015. J Acad Nutr Diet. 2018;118:1591–602.
Reedy J, Wirfält E, Flood A, Mitrou PN, Krebs-Smith SM, Kipnis V, et al. Comparing 3 dietary pattern methods—cluster analysis, factor analysis, and index analysis—with colorectal cancer risk: the NIH-AARP diet and health study. Am J Epidemiol. 2010;171:479–87.
Romaguera D, Vergnaud A-C, Peeters PH, van Gils CH, Chan DSM, Ferrari P, et al. Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study. Am J Clin Nutr. 2012;96:150–63.
Molina-Montes E, Sánchez M-J, Buckland G, Bueno-de-Mesquita HB, Weiderpass E, Amiano P, et al. Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort. Br J Cancer. 2017;116:811–20.
Kabat GC, Matthews CE, Kamensky V, Hollenbeck AR, Rohan TE. Adherence to cancer prevention guidelines and cancer incidence, cancer mortality, and total mortality: a prospective cohort study. Am J Clin Nutr. 2015;101:558–69.
Lynch SM, Vrieling A, Lubin JH, Kraft P, Mendelsohn JB, Hartge P, et al. Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. Am J Epidemiol. 2009;170:403–13.
Rawla P, Thandra KC, Sunkara T. Pancreatic cancer and obesity: epidemiology, mechanism, and preventive strategies. Clin J Gastroenterol. 2019;12:285–91.
Genkinger JM, Kitahara CM, Bernstein L, de Berrington de Gonzalez A, Brotzman M, Elena JW, et al. Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies. Ann Oncol. 2015;26:2257–66.
Patel P, Abate N. Body fat distribution and insulin resistance. Nutrients. 2013;5:2019–27.
Taylor R. Insulin resistance and type 2 diabetes. Diabetes. 2012;61:778–9.
Song S, Wang B, Zhang X, Hao L, Hu X, Li Z, et al. Long-term diabetes mellitus is associated with an increased risk of pancreatic cancer: a meta-analysis. PLoS ONE. 2015;10:e0134321.
Chiolero A, Faeh D, Paccaud F, Cornuz J. Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr. 2008;87:801–9.
Molenaar EA, Massaro JM, Jacques PF, Pou KM, Ellison RC, Hoffmann U, et al. Association of lifestyle factors with abdominal subcutaneous and visceral adiposity: the Framingham Heart Study. Diabetes Care Diabetes Care. 2009;32(505):505–10.
Hernán MA. The hazards of hazard ratios. Epidemiol Camb Mass. 2010;21:13–5.
White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ. Age and cancer risk. Am J Prev Med. 2014;46:S7–15.
Akinyemiju T, Ogunsina K, Okwali M, Sakhuja S, Braithwaite D. Lifecourse socioeconomic status and cancer-related risk factors: analysis of the WHO study on global ageing and adult health (SAGE). Int J Cancer. 2017;140:777–87.
Wilson LF, Antonsson A, Green AC, Jordan SJ, Kendall BJ, Nagle CM, et al. How many cancer cases and deaths are potentially preventable? Estimates for Australia in 2013. Int J Cancer. 2018;142:691–701.
Acknowledgements
We thank Carine Biessy and Bertrand Hemon for their technical support and contribution to this work. We are also grateful to all the EPIC participants who have been part of the project and to the many other members of the study teams who have enabled this research.
Funding
This work was supported by the Direction Générale de la Santé (French Ministry of Health) (Grant GR-IARC-2003-09-12-01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l’Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France); the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum, and the Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece); the Italian Association for Research on Cancer and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (The Netherlands); the Health Research Fund, Regional Governments of Andalucýa, Asturias, Basque Country, Murcia (Project 6236) and Navarra, Instituto de Salud Carlos III, Redes de Investigacion Cooperativa (RD06/0020) (Spain); the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency, and the Wellcome Trust (UK). This work was part of Sabine Naudin’s PhD at Claude Bernard Lyon I University (France), funded by Région Auvergne Rhône-Alpes, ADR 2016 (France).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Disclaimer Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Naudin, S., Viallon, V., Hashim, D. et al. Healthy lifestyle and the risk of pancreatic cancer in the EPIC study. Eur J Epidemiol 35, 975–986 (2020). https://doi.org/10.1007/s10654-019-00559-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10654-019-00559-6