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Cancer Epidemiology Biomarkers & Prevention Vol. 14, 1571-1573, June 2005
© 2005 American Association for Cancer Research


Null Results in Brief

Lack of Association of Physical Activity and Obesity with Incident Pancreatic Cancer in Elderly Women

Penny J. Sinner, Kathryn H. Schmitz, Kristin E. Anderson and Aaron R. Folsom

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota

Requests for reprints: Kathryn H. Schmitz, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Suite 300, 1300 South Second Street, Minneapolis, MN 55454-1015. Phone: 612-625-8056; Fax: 612-624-0315. E-mail: schmitz{at}epi.umn.edu


    Introduction
 Top
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Pancreatic cancer is relatively uncommon in the United States, but it is rapidly fatal with <5% of cases surviving 5 years (1). Little is known about its etiology; cigarette smoking is the only modifiable risk factor consistently linked to pancreatic cancer (2).

Animal models have suggested that insulin and insulin resistance may play roles in the etiology of pancreatic cancer (3, 4) and epidemiologic studies have shown an association between diabetes mellitus and increased risk of pancreatic cancer (5-7). Obesity, measured by body mass index (BMI) and waist-to-hip ratio (WHR), and physical activity can play roles in both insulin resistance and type II diabetes (8, 9).

Two recent prospective studies have examined pancreatic cancer incidence in relation to obesity and physical activity: Michaud et al. reported that individuals with a high BMI or low level of moderate physical activity were at an increased risk of pancreatic cancer (10), whereas Lee et al. reported that BMI and physical activity were not associated with pancreatic cancer risk (11). The Iowa Women's Health Study was used to analyze the association of obesity and physical activity with pancreatic cancer risk in older women.


    Materials and Methods
 Top
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
As described elsewhere (12, 13) in January 1986, the Iowa Women's Health Study mailed questionnaires to nearly 100,000 randomly selected women ages 55 to 69 years, who had a valid Iowa driver's license in 1985. The 41,836 (42%) women who returned questionnaires were subsequently followed for mortality and cancer incidence. The University of Minnesota's Institutional Review Board approved this research study.

Vital status was obtained through follow-up questionnaires in 1987, 1989, 1992, and 1997 and through the National Death Index. New pancreatic cancers (International Classification of Diseases for Oncology Second Edition code C25) were ascertained through the Iowa Cancer Registry, which is part of the national Surveillance, Epidemiology, End Results program. Subjects with a history of cancer other than nonmelanoma skin cancer at baseline were excluded (n = 3830). Pancreatic cancer cases determined to be islet cell carcinomas (n = 1), neuorendocrine carcinomas (n = 1), and leiomyosarcomas (n = 2) were also excluded. After these exclusions, 38,002 participants at risk, including 209 who developed pancreatic cancer through December 31, 2001, were included in this analysis. A sensitivity analysis was done to exclude participants diagnosed with pancreatic cancer before January 1, 1988 (n = 14). Results did not differ for the sensitivity analysis and therefore these cases of pancreatic cancer were included.

Methods of collection for physical activity, BMI at age 18, 30, 40, 50, and at baseline, and WHR, have been published elsewhere (12-14). Measures of baseline weight, height, and waist and hip circumferences were generally accurate and reliable (14). Participants were asked three questions about whether they participated in leisure time exercise and, if so, the frequency of moderate and heavy activities. The latter two questions were combined to create a three-level activity score.

Baseline characteristics were compared among participants who developed pancreatic cancer and those who did not using Pearson's {chi}2 test or the t test. Age-adjusted and multivariate-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were computed using proportional hazards regression. Besides study variables mentioned previously, potential confounders that showed an association with both pancreatic cancer and the study variables (P < 0.10) were included in the multivariate models. These confounders included age, smoking status, and multivitamin use. All statistical analyses were done using SAS 8 software (15).


    Results
 Top
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Compared with women who remained free of pancreatic cancer, women who developed pancreatic cancer were 0.8 years older (P = 0.01), two thirds more likely to be smokers (P = 0.002), twice as likely to have diabetes (P = 0.0006), and less likely to be taking a multivitamin daily (P = 0.02; Table 1). There were no differences between groups in mean BMI, WHR, or physical activity measures.


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Table 1. Baseline characteristics of women who did or did not develop pancreatic cancer, 1986

 
Age- and multivariate-adjusted pancreatic cancer incidence was not associated with any obesity category (Table 2). Women with a BMI ≥ 30 kg/m2 at baseline had a HR of 1.14 (95% CI, 0.81-1.62) compared with a BMI < 25 kg/m2. Women in the highest tertile of WHR had a HR of 1.12 (95% CI, 0.81-1.55) compared with the lowest WHR tertile. Multivariate-adjusted pancreatic cancer incidence also was not associated with obesity based on self-recalled weights at age 18, 30, or 50, although obesity at age 40 unexpectedly carried a pancreatic cancer HR of 1.72 (95% CI, 1.12-2.63; results not shown).


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Table 2. HRs and 95% CIs for incident pancreatic cancer in relation to BMI, waist circumference, WHR, and physical activity

 
There was no association between physical activity and pancreatic cancer (Table 2). Women with a high versus low activity level at baseline had a HR of 1.29 (95% CI, 0.93-1.77). Finally, there was no association between body size and physical activity categories, considered jointly, and pancreatic cancer incidence (results not shown).


    Discussion
 Top
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
This large cohort study of elderly women provides evidence that physical inactivity and obesity are not risk factors for pancreatic cancer. With our sample size, we had 85% power to detect a HR of ≥1.5. Limitations of our study were a short physical activity instrument, although one that does relate to CHD mortality (12), and single measures of exposure.

Recent epidemiologic research has been inconclusive regarding the associations of physical activity and obesity with pancreatic cancer. Of seven studies on physical activity and pancreatic cancer, four reported no association (11, 16-18) and three reported an inverse association (10, 19, 20). Since 2000, six studies of obesity and pancreatic cancer incidence reported no association (11, 16, 17, 19, 21, 22), whereas six others reported a positive association (7, 10, 20, 23-25).

There is a plausible biological pathway through which physical inactivity and obesity could lead to pancreatic cancer. Obesity and physical inactivity are well-established risk factors for insulin resistance and type II diabetes (8, 9). Insulin resistance has been shown to induce islet cell proliferation and turnover, which in turn promotes pancreatic carcinogenesis (3, 26).

The next step for research in this area may be to pool data across several cohort studies that have addressed this hypothesis to increase power. Nevertheless, in this cohort, there was no evidence that obesity or physical inactivity play a role in pancreatic cancer etiology.


    Footnotes
 
Grant support: National Cancer Institute, U.S. Department of Health and Human Services grant R01 CA39742.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 1/17/05; accepted 3/14/05.


    References
 Top
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Ries LAG, Eisner MP, Kosary CL, et al. editors. SEER cancer statistics review, 1975-2001. Bethesda (MD): National Cancer Institute; 2004. [cited 2004 Nov 22]. Available from: http://seer.cancer.gov/csr/1975_2001/, 2004.
  2. Michaud DS. Epidemiology of pancreatic cancer. Minerva Chir 2004;59:99–111.[Medline]
  3. Schneider MB, Matsuzaki H, Haorah J, et al. Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology 2001;120:1291–6.[Medline]
  4. Kazakoff K, Cardesa T, Liu J, et al. Effects of voluntary physical exercise on high-fat diet-promoted pancreatic carcinogenesis in the hamster model. Nutr Cancer 1996;26:265–79.[Medline]
  5. Bonelli L, Aste H, Bovo P, et al. Exocrine pancreatic cancer, cigarette smoking, and diabetes mellitus: a case-control study in northern Italy. Pancreas 2003;27:143–9.[CrossRef][Medline]
  6. Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, Albanes D. A prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland). Cancer Causes Control 2002;13:417–26.[CrossRef][Medline]
  7. Silverman DT. Risk factors for pancreatic cancer: a case-control study based on direct interviews. Teratog Carcinog Mutagen 2001;21:7–25.[CrossRef][Medline]
  8. Steyn NP, Mann J, Bennett PH, et al. Diet, nutrition and the prevention of type 2 diabetes. Public Health Nutr 2004;7:147–65.[CrossRef][Medline]
  9. Vegt F, Dekker JM, Jager A, et al. Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population. JAMA 2001;285:2109–13.[Abstract/Free Full Text]
  10. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 2001;286:921–9.[Abstract/Free Full Text]
  11. Lee I-M, Sesso HD, Oguma Y, Paffenbarger RS. Physical activity, body weight, and pancreatic cancer mortality. Br J Cancer 2003;88:679–83.[CrossRef][Medline]
  12. Kushi LH, Fee RM, Folsom AR, Mink PJ, Anderson KE, Sellers TA. Physical activity and mortality in postmenopausal women. JAMA 1997;277:1287–92.[Abstract]
  13. Prineas RJ, Folsom AR, Kaye SA. Central adiposity and increased risk of coronary artery disease mortality in older women. Ann Epidemiol 1993;3:35–41.[Medline]
  14. Kushi LH, Kaye SA, Folsom AR, Soler JT, Prineas RJ. Accuracy and reliability of self-measurement of body girths. Am J Epidemiol 1988;128:740–8.[Abstract/Free Full Text]
  15. The analysis for this paper was generated using SAS/STAT software, version 8 of the SAS system. Copyright © 1999 SAS Institute Inc. Cary (NC).
  16. Hanley AJ, Johnson KC, Villeneuve PJ, Mao Y. Physical activity, anthropometric factors, and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int J Cancer 2001;94:140–7.[CrossRef][Medline]
  17. Nilsen TL, Vatten LJ. A prospective study of lifestyle factors and the risk of pancreatic cancer in Nord-Trondelag, Norway. Cancer Causes Control 2000 Aug;11:645–52.[CrossRef][Medline]
  18. Garfinkel L, Stellman SD. Mortality by relative weight and exercise. Cancer 1988;62:1844–50.[CrossRef][Medline]
  19. Inoue M, Tajima J, Takezaki T, et al. Epidemiology of pancreatic cancer in Japan: a nested case-control study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC). Int J Epidemiol 2003;32:257–62.[Abstract/Free Full Text]
  20. Isaksson B, Jonsson F, Pedersen NL, Larsson J, Feychting M, Permert J. Lifestyle factors and pancreatic cancer risk: a cohort study from the Swedish Twin Registry. Int J Cancer 2002;98:480–2.[CrossRef][Medline]
  21. Wolk A, Gridley G, Swensson M, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 2001;12:13–21.[CrossRef][Medline]
  22. Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 2000;283:2552–8.[Abstract/Free Full Text]
  23. Pan SY, Johnson KC, Ugnat AM, Wen SW, Mao Y. Association of obesity and cancer risk in Canada. Am J Epidemiol 2004;159:259–68.[Abstract/Free Full Text]
  24. Calle EE, Rodriquez C, Walker-Thurmond K, Thun MJ. Overweight, obesity and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003;348:1625–38.[Abstract/Free Full Text]
  25. Coughlin SS, Calle EE, Patel AV, Thun MJ. Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control 2000;11:915–23.[CrossRef][Medline]
  26. Pour PM, Kazakoff K. Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model. Am J Pathol 1996;149:1017–25.[Abstract]



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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation