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Healthy lifestyle and the risk of pancreatic cancer in the EPIC study

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.

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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

  1. 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.

    CAS  PubMed  Article  Google Scholar 

  2. 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.

    CAS  Article  Google Scholar 

  3. 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.

    CAS  Article  Google Scholar 

  4. 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.

    PubMed  Article  Google Scholar 

  5. Lindquist CM, Miller FH, Hammond NA, Nikolaidis P. Pancreatic cancer screening. Abdom Radiol N Y. 2018;43:264–72.

    Article  Google Scholar 

  6. 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.

    Google Scholar 

  7. Maisonneuve P, Lowenfels AB. Risk factors for pancreatic cancer: a summary review of meta-analytical studies. Int J Epidemiol. 2015;44:186–98.

    PubMed  Article  Google Scholar 

  8. 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.

  9. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  10. 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.

    PubMed  Article  Google Scholar 

  11. 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.

    PubMed  Article  Google Scholar 

  12. 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.

    CAS  PubMed  Article  Google Scholar 

  13. 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.

    PubMed  Article  Google Scholar 

  14. Catsburg C, Miller AB, Rohan TE. Adherence to cancer prevention guidelines and risk of breast cancer. Int J Cancer. 2014;135:2444–52.

    CAS  PubMed  Article  Google Scholar 

  15. 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.

    PubMed  Article  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  19. 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.

    CAS  PubMed  Article  Google Scholar 

  20. 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.

    CAS  PubMed  Article  Google Scholar 

  21. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  22. 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.

    CAS  PubMed  Article  Google Scholar 

  23. 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.

    PubMed  Article  Google Scholar 

  24. 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.

    PubMed  Article  Google Scholar 

  25. 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.

    PubMed  Article  Google Scholar 

  26. 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.

    PubMed  Article  CAS  Google Scholar 

  27. 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.

    CAS  PubMed  Article  Google Scholar 

  28. 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.

  29. 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.

    Article  Google Scholar 

  30. 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.

    CAS  PubMed  Article  Google Scholar 

  31. 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.

    PubMed  Article  Google Scholar 

  32. 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.

    PubMed  Article  Google Scholar 

  33. 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.

    CAS  PubMed  Article  Google Scholar 

  34. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  35. 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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika. 1982;69:239–41.

    Article  Google Scholar 

  37. Barendregt JJ, Veerman JL. Categorical versus continuous risk factors and the calculation of potential impact fractions. J Epidemiol Community Health. 2010;64:209–12.

    PubMed  Article  Google Scholar 

  38. Efron B, Tibshirani R. Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci. 1986;1:54–75.

    Google Scholar 

  39. Lambert PC, Royston P. Further development of flexible parametric models for survival analysis. Stata J. 2009;9(2):21.

    Article  Google Scholar 

  40. StataCorp. Stata statistical software: release 14. College Station: StataCorp LP; 2015.

    Google Scholar 

  41. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  42. 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.

    PubMed  Article  Google Scholar 

  43. 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.

    CAS  PubMed  Article  Google Scholar 

  44. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  45. 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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 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.

    PubMed  PubMed Central  Article  Google Scholar 

  47. Rawla P, Thandra KC, Sunkara T. Pancreatic cancer and obesity: epidemiology, mechanism, and preventive strategies. Clin J Gastroenterol. 2019;12:285–91.

    PubMed  Article  Google Scholar 

  48. 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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. Patel P, Abate N. Body fat distribution and insulin resistance. Nutrients. 2013;5:2019–27.

    PubMed  PubMed Central  Article  Google Scholar 

  50. Taylor R. Insulin resistance and type 2 diabetes. Diabetes. 2012;61:778–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. 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.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  52. 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.

    CAS  PubMed  Article  Google Scholar 

  53. 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.

    PubMed  Article  Google Scholar 

  54. Hernán MA. The hazards of hazard ratios. Epidemiol Camb Mass. 2010;21:13–5.

    Article  Google Scholar 

  55. White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ. Age and cancer risk. Am J Prev Med. 2014;46:S7–15.

    PubMed  PubMed Central  Article  Google Scholar 

  56. 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.

    CAS  PubMed  Article  Google Scholar 

  57. 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.

    CAS  PubMed  Article  Google Scholar 

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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).

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Correspondence to Pietro Ferrari.

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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

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Keywords

  • Pancreatic cancer
  • Healthy Lifestyle Index
  • Population attributable fraction
  • EPIC
  • Prospective study