CEBP Meeting Calendar Frontiers in Basic Cancer Research
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 Meeting Abstracts Online
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Berrington de González, A.
Right arrow Articles by Riboli, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berrington de González, A.
Right arrow Articles by Riboli, E.
Cancer Epidemiology Biomarkers & Prevention Vol. 15, 879-885, May 2006
© 2006 American Association for Cancer Research

Anthropometry, Physical Activity, and the Risk of Pancreatic Cancer in the European Prospective Investigation into Cancer and Nutrition

Amy Berrington de González1, Elizabeth A. Spencer1, H. Bas Bueno-de-Mesquita2, Andrew Roddam1, Rachel Stolzenberg-Solomon4, Jytte Halkjær5, Anne Tjønneland5, Kim Overvad6, Francoise Clavel-Chapelon7, Marie-Christine Boutron-Ruault7, Heiner Boeing8, Tobias Pischon8, Jakob Linseisen9, Sabine Rohrmann9, Antonia Trichopoulou10, Vassiliki Benetou10, Aristoteles Papadimitriou10, Valeria Pala11, Domenico Palli12, Salvatore Panico13, Rosario Tumino14, Paolo Vineis15, Hendriek C. Boshuizen3, Marga C. Ocke2, Petra H. Peeters16, Eiliv Lund17, Carlos A. Gonzalez18, Nerea Larrañaga19, Carmen Martinez-Garcia20, Michelle Mendez18, Carmen Navarro21, J. Ramón Quirós22, María-José Tormo21, Göran Hallmans23, Weimin Ye24, Sheila A. Bingham25, Kay-Tee Khaw26, Naomi Allen1, Tim J. Key1, Mazda Jenab27, Teresa Norat27, Pietro Ferrari27 and Elio Riboli27

1 Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom; 2 Center for Nutrition and Health and 3 Center for Information Technology and Methodology, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; 4 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; 5 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; 6 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark; 7 E3N-Institut National de la Sante et de la Recherche Medicale, Nutrition, Hormones, and Cancer Unit, Institut Gustave Roussy, Villejuif, France; 8 German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; 9 Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany; 10 Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Greece; 11 Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy; 12 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Centre, Scientific Institute of Tuscany, Florence, Italy; 13 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy; 14 Cancer Registry, Azienda Ospedaliera Civile-M.P. Arezzo, Ragusa, Italy; 15 University of Torino, Italy and Imperial College, London, United Kingdom; 16 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; 17 Institute of Community Medicine, University of Tromsø, Tromsø, Norway; 18 Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain; 19 Public Health Division of Gipuzkoa, Health Department of the Basque Country, San Sebastian, Spain; 20 Andalusian School of Public Health, Granada, Spain; 21 Epidemiology Department, Murcia Health Council, Murcia, Spain; 22 Health and Health Planning Directorate, Asturias, Spain; 23 Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden; 24 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 25 Medical Research Council Dunn Human Nutrition Unit; 26 Clinical Gerontology Unit, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom; and 27 IARC-WHO, Lyon, France

Requests for reprints: Amy Berrington de González, Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom. Phone: 44-1865-289600; Fax: 44-1865-289610. E-mail: aberring{at}jhsph.edu


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Tobacco smoking is the only established risk factor for pancreatic cancer. Results from several epidemiologic studies have suggested that increased body mass index and/or lack of physical activity may be associated with an increased risk of this disease. We examined the relationship between anthropometry and physical activity recorded at baseline and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (n = 438,405 males and females age 19-84 years and followed for a total of 2,826,070 person-years). Relative risks (RR) were calculated using Cox proportional hazards models stratified by age, sex, and country and adjusted for smoking and self-reported diabetes and, where appropriate, height. In total, there were 324 incident cases of pancreatic cancer diagnosed in the cohort over an average of 6 years of follow-up. There was evidence that the RR of pancreatic cancer was associated with increased height [RR, 1.74; 95% confidence interval (95% CI), 1.20-2.52] for highest quartile compared with lowest quartile (Ptrend = 0.001). However, this trend was primarily due to a low risk in the lowest quartile, as when this group was excluded, the trend was no longer statistically significant (P = 0.27). A larger waist-to-hip ratio and waist circumference were both associated with an increased risk of developing the disease (RR per 0.1, 1.24; 95% CI, 1.04-1.48; Ptrend = 0.02 and RR per 10 cm, 1.13; 95% CI, 1.01-1.26; Ptrend = 0.03, respectively). There was a nonsignificant increased risk of pancreatic cancer with increasing body mass index (RR, 1.09; 95% CI, 0.95-1.24 per 5 kg/m2), and a nonsignificant decreased risk with total physical activity (RR, 0.82; 95% CI, 0.50-1.35 for most active versus inactive). Future studies should consider including measurements of waist and hip circumference, to further investigate the relationship between central adiposity and the risk of pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(5):879–85)


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Pancreatic cancer is the sixth most common cause of cancer mortality in the European Union countries and is responsible for ~55,000 deaths there every year (1). Tobacco smoking is the only established cause of this invariably fatal disease (2). Diabetes is also probably a cause of pancreatic cancer (3), and it has been hypothesized, therefore, that other factors that are associated with glucose intolerance, such as obesity and lack of physical activity, may also increase the risk of developing pancreatic cancer. Several prospective epidemiologic studies have found that a high body mass index (BMI; refs. 4-6) and/or a lack of physical activity (6, 7) are associated with an increased risk of pancreatic cancer incidence or mortality, and these associations seem to be independent of a prior history of diabetes. Three of these four prospective studies were conducted in the United States (4-6), and the fourth was a study of male smokers in Finland (7).

The purpose of the current study was to examine the relationship between anthropometric factors and physical activity and the risk of developing pancreatic cancer in a large European cohort, the European Prospective Investigation into Cancer and Nutrition. The European Prospective Investigation into Cancer and Nutrition is a multicenter study designed primarily to investigate the relationship between nutrition and cancer in 10 European countries. The study has measured anthropometric variables for most participants at baseline and is one of the first epidemiologic studies of pancreatic cancer to also include measurements of hip and waist circumference.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The European Prospective Investigation into Cancer and Nutrition is a multicenter prospective cohort study consisting of 23 centers from Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom. The study populations were mostly age 35 to 70 years and were recruited from the general population residing in a specific geographic region (a town or a province). The exceptions were the French cohort (health insurance scheme for school employees), the Utrecht (the Netherlands) and Florence (Italy) cohorts (women attending breast cancer screening), components of the Italian and Spanish cohorts (based on blood donors), and most of the Oxford (United Kingdom) cohort (based on vegetarian and health-conscious volunteers living in the United Kingdom). Eligible subjects were invited to participate in the study, and those who accepted gave informed consent and completed lifestyle questionnaires. In most centers, subjects were then invited to a center to provide a blood sample and to have anthropometric measurements taken. The lifestyle questionnaires included questions on education and socioeconomic status, occupation, history of previous illness, lifetime history of consumption of tobacco and alcoholic beverages, and physical activity. The methods have been reported in full by Riboli et al. (8).

Follow-up and Case Ascertainment
Follow-up was based on population cancer registries in seven of the participating countries: Denmark, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom. In France, Germany, and Greece, a combination of methods were used, including health insurance records, cancer and pathology registries, and active follow-up through participants and their next of kin. Mortality data were also obtained from either the cancer registry or mortality registries at the regional or national level. Participants were followed from study entry (1991-2000) until first pancreatic cancer diagnosis, death, emigration, or end of the follow-up period. The current analysis was based on the central dataset held at the International Agency for Research on Cancer data set, updated to April 2004. For centers using cancer registry data, censoring dates for complete follow-up were December 1999 (Turin, Italy), December 2000 (Asturias and Murcia, Spain; Cambridge, United Kingdom; Bilthoven, the Netherlands), December 2001 (Florence, Varese, Ragusa, and Naples, Italy; Granada, Norway, Navarra, and San Sebastian, Spain; Oxford, United Kingdom; Malmö, Sweden), December 2002 (Umeå, Sweden; Aarhus and Copenhagen, Denmark), and June 2003 (Utrecht, the Netherlands). Subjects were censored at the date of pancreatic cancer diagnosis, date of death, loss to follow-up, or censoring date, whichever came first. For the three countries using individually based follow-up (France, Greece, and Germany), the end of follow-up was considered to be the date of last known contact, or date of diagnosis, or date of death, whichever came first. The percentage of subjects lost to follow-up was 1.6%.

Cancer incidence data were coded according to International Classification of Diseases-Oncology 2nd edition and mortality data according to the International Classification of Diseases 10th edition. Incident cases of pancreatic cancer reported to the central database during the follow-up period were eligible to be included in the present study. In total, 356 subjects were diagnosed with incident pancreatic cancer over the follow-up period. Twenty-nine cases were excluded from analyses for the following reasons: cases where the diagnosis date was after the censoring date (n = 1), cases of endocrine or lymphoid origin (n = 14), cases where it was uncertain whether the pancreatic cancer was the primary tumor (n = 14). As there were only three incident cases of pancreatic cancer over the follow-up period reported in the center from Norway, this center was excluded from the current analyses.

Anthropometry
All centers had measured anthropometric factors at baseline with the exception of the centers in France and the Oxford health-conscious volunteers. For the centers in France, self-reported baseline values for height and weight were available but no values for hip and waist circumference. The self-reported measures for the Oxford health-conscious volunteers were corrected for possible reporting bias. The corrections were obtained from age- and sex-specific regression of measured anthropometry onto self-reported anthropometry from the Oxford subjects recruited through general practitioners, for whom both measured and self-reported baseline anthropometry were available (9). The centers in Umeå, Sweden had measured height and weight at baseline but had not collected values for hip and waist circumference either.

Weight and height were recorded to the nearest 0.1 kg and 0.1 or 0.5 cm, respectively (9). Waist circumference was measured either at the narrowest torso circumference (Italy; Cambridge, United Kingdom; and Utrecht, the Netherlands) or at the midpoint between the lower ribs and iliac crest (Bilthoven, the Netherlands; Potsdam, Germany; Malmö, Sweden; and Oxford, United Kingdom). In Spain, Greece, Denmark, and Heidelberg, Germany, a combination of methods was used, although the majority of participants were measured at the narrowest circumference. Hip circumference was measured at the widest circumference (Italy; Spain; Bilthoven, the Netherlands; Greece; and Malmö, Sweden) or over the buttocks (United Kingdom; Utrecht, the Netherlands; Germany; and Denmark).

The anthropometric data were adjusted to reduce heterogeneity due to protocol differences in clothing worn during measurement. In most Italian centers, Spain, Germany, and Denmark, weight was measured in light underwear. In the centers of France; Turin; Umeå, Sweden; and Utrecht, the Netherlands, subjects wore normal clothing without shoes. In the remaining centers (Oxford-GP and Cambridge, United Kingdom; Bilthoven, the Netherlands; Greece; Malmö, Sweden), weighing was undertaken after removal of heavier sweaters or indoor jackets and emptying heavy objects from pockets (light clothing). For subjects who wore normal clothing without shoes, correction factors of –1.5 kg for weight and –2.0 cm for circumferences were adopted. In centers where weight was measured in light clothing, the adjustment for weight was –1.0 kg.

Physical Activity
In each center, work, leisure-time/home, and vigorous physical activity were assessed at baseline as part of the standardized lifestyle questionnaire (10). The core physical activity questionnaire used by most centers included questions on type of physical activity at work and the number of hours spent per week on vigorous physical activity and a number of specific recreational and household activities, including walking, housework, sport, gardening, and do it yourself. A summary "leisure time" physical activity variable was created by summing the number of hours spent per week in summer or winter on recreational and household or do-it-yourself physical activities. The intensities of these recorded activities were estimated from published values, and from these, summary leisure time metabolic equivalent (MET) levels were calculated as the sum of the MET hours/wk. An "overall" physical activity summary was then created by combining levels of physical activity at work with the summary measure of "METs leisure time" physical activity.

Statistical Methods
Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (95% CI) of pancreatic cancer incidence for each body measure and physical activity category. Age at study entry was used as the underlying (primary dependent) time variable, with entry time defined as the subject's age in days at recruitment and exit time defined as the subject's age in days at pancreatic cancer diagnosis or censoring. Analyses were restricted to subjects who were aged between 19 and 84 years at study entry.

BMI was calculated as weight divided by height squared (kg/m2). Subjects with BMI between 20.0 and 22.4 kg/m2 were used as the baseline category and compared with categories of BMI of <20.0, 22.5 to 24.9, 25 to 27.4, 27.5 to 29.9, and ≥30 kg/m2. The waist and hip circumferences of each participant were used to construct a waist-to-hip ratio. Subjects were categorized according to sex-specific quartiles of height, weight, waist and hip circumference, and waist-to-hip ratio defined over the entire cohort, and the first quartile was used as the reference category. All models were stratified by sex, 5-year age groups at recruitment, and by country, and multivariate models were adjusted for smoking [never, past smokers (time since stopping: <15 and ≥15 years), and current smokers (intensity: <10, 10-19, and ≥20 cigarettes per day)] and self-reported diabetes (yes/no). Analyses of weight, waist and hip circumference, and waist-to-hip ratio were also adjusted for height. Subjects with missing values for smoking status and diabetes were excluded from all analyses (n = 28,532). Trend tests were calculated using the continuous anthropometric variables and across the categories of physical activity. Heterogeneity between countries was tested using the method of empirically weighed least squares with the weights defined as the inverse of the variance of the log relative risk (11).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The analysis cohort included 438,405 subjects age between 19 and 84 years at baseline who were followed up for a total of 2,934,501 person years. Of the 324 included incident cases of pancreatic cancer, 152 cases were in males for which the median age at diagnosis was 61 years, and 172 cases were in females with a median age at diagnosis of 63 years (Table 1 ). Median height was lowest for Spanish males and for Greek females, and highest for males and females from the Netherlands. Median BMI was lowest in the U.K. health-conscious males and French females and highest in Spanish male and Greek female participants. The lowest proportion of subjects classified as very active were females from France and Swedish males, whereas the highest proportions were males and females from the Netherlands.


View this table:
[in this window]
[in a new window]
  		Table 1. Distribution of pancreatic cancer cases and noncases and BMI and physical activity according to country and age group

 
Anthropometry
The associations between anthropometry and smoking and diabetes status, the potential confounding factors, were examined in the cohort overall. There was evidence that being taller was associated with a decreased probability of being diabetic and with a slightly increased probability of being a current or past smoker, whereas higher BMI was associated with an increased probability of being diabetic and of being a past smoker but with a lower probability of being a current smoker (Table 2 ). A higher waist-to-hip ratio was also associated with an increased probability of being diabetic and with a slightly increased probability of being a current smoker.


View this table:
[in this window]
[in a new window]
  		Table 2. Associations between anthropometry, physical activity and diabetes and smoking status

 
The SR of pancreatic cancer was associated with increased height (RR, 1.74; 95% CI, 1.20-2.52) for the highest to lowest quartile (Ptrend = 0.001; Table 3 ). However, this significant trend was primarily due to the low risk in the lowest quartile, as when this group was excluded, the RR per cm increase was no longer statistically significant (Ptrend = 0.27). After adjustment for confounding factors, there was no significant relationship between increased weight and the risk of pancreatic cancer (RR per 5 kg increase, 1.05; 95% CI, 0.99-1.10; Table 3), neither was there evidence that increased BMI was associated with a significantly increased risk of pancreatic cancer (RR per 5 kg/m2, 1.09; 95% CI, 0.95-1.24). A higher waist circumference and waist-to-hip ratio were both associated with a slightly increased risk of developing pancreatic cancer, and the trends were statistically significant (RR per 10-cm increase, 1.13; 95% CI, 1.01-1.26; Ptrend = 0.03 and RR per 0.1 increase, 1.24; 95% CI, 1.04-1.48; Ptrend = 0.02, respectively; Table 3). There was no significant increase in RR with increasing hip circumference.


View this table:
[in this window]
[in a new window]
  		Table 3. RR and 95% CI of pancreatic cancer according to anthropometric factors

 
Generally, the adjustments for smoking and diabetes, and where appropriate, height, decreased the relative risk estimates slightly (Table 3). There was no evidence of significant effect modification by smoking or diabetic status, although the number of subjects with self-reported diabetes as baseline was relatively small; thus, tests for statistical interaction lacked power (Table 4 ). The RRs for all the anthropometric factors varied somewhat between males and females, but none of these differences were statistically significant at the 0.05 level when interaction terms were included in the proportional hazards model. The consistency of findings across countries was examined by estimating the relative risks for the continuous variables. There was no evidence of significant heterogeneity between the results from different countries for any of the anthropometric factors (Table 3).


View this table:
[in this window]
[in a new window]
  		Table 4. RR and 95% CI of pancreatic cancer according to anthropometric factors by smoking and diabetes status

 
All the above analyses were repeated with exclusion of the first 2 years of follow-up to assess whether an association with preexisting disease might have influenced the results. The findings were broadly similar to those from the full analysis, but the magnitude of the risk of developing pancreatic cancer with higher waist circumference and waist-to-hip ratio were increased to some extent after this exclusion (Table 5 ). The mean waist-to-hip ratio at baseline of the female cases who were diagnosed within 2 years of study entry was 0.80 compared with 0.83 for those cases who were diagnosed >2 years after study entry (t test, P = 0.009). Similarly, the mean waist circumference of the females cases diagnosed within 2 years of study entry was lower than those diagnosed later (81 cm compared with 86 cm; t test, P = 0.04). No such differences were present, however, for the male cases (mean waist-to-hip ratio = 0.96 and mean waist circumference = 97 cm for <2 and ≥2 years to diagnosis, respectively).


View this table:
[in this window]
[in a new window]
  		Table 5. RR and 95% CI of pancreatic cancer according to anthropometric factors, excluding the first 2 years follow-up

 
Physical Activity
Overall, subjects who were most active, according to the summary physical activity index, were younger (Table 1) and were less likely to have ever smoked (Table 2). There was no evidence that the reported number of hours of vigorous physical activity or any of the other composite physical activity measures were related to the risk of pancreatic cancer, either before or after adjustment for smoking and diabetes (Table 6 ) or after exclusion of the first 2 years of follow-up (data not shown). Neither was there evidence of effect modification between physical activity and obesity, as measured by BMI or waist-to-hip ratio (data not shown).


View this table:
[in this window]
[in a new window]
  		Table 6. RR and 95% CI of pancreatic cancer in relation to physical activity

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this large multicenter prospective study, we found that both a higher waist circumference and waist-to-hip ratio were associated with an increased risk of developing pancreatic cancer, but increased BMI and level of physical activity were not significantly associated with the risk of developing the increase. There was also some evidence of an association between increased height and pancreatic cancer risk.

There have been at least seven prospective and six retrospective studies published on the risk of pancreatic cancer and BMI, and together, they provide evidence that obesity, measured by an increased BMI, may be weakly associated with risk (12). In the current study, although there was no statistically significant relationship between increased BMI and the risk of pancreatic cancer, the relative risk per 5 kg/m2 of 1.09 (95% CI, 0.95-1.24) was consistent with the combined findings from previous studies (summary RR per 5 kg/m2, 1.16; ref. 12). Two measures of central adiposity, increased waist circumference and waist-to-hip ratio, however, were significantly related to the risk of developing pancreatic cancer. Two other studies have published results for central adiposity and pancreatic cancer, and both found evidence of increased risks. Larsson et al. found evidence of an increased risk with increasing self-reported waist circumference in a Swedish cohort study. In the U.S. Cancer Prevention Study II, Patel et al. found that subjects who reported a tendency for central weight gain were at increased risk of pancreatic cancer compared with those who reported peripheral weight gain (RR, 1.45; 95% CI, 1.02-2.07; ref. 14). In the current study, the magnitude of the risk and the strength of the trend for these measures of central adiposity increased when the first 2 years of follow-up were excluded, to remove the possible effect of prediagnostic symptoms.

Three prospective studies have directly investigated abnormal glucose metabolism and the risk of pancreatic cancer. All reported increased risks with increasing levels of glucose intolerance not just a raised risk for those who were clinically diabetic (5, 15, 16). Central adiposity is associated with glucose intolerance and is a risk factor for diabetes (17-19), hence concomitantly increased insulin levels may be the mechanism through which central adiposity increases pancreatic cancer risk. Adjustment for self-reported diabetes status did slightly reduce the magnitude of the association between both measures of central adiposity and the risk of pancreatic cancer, but there was still a significant association in those who did not report being diabetic at study entry. This could be evidence that any level of glucose intolerance, not just clinical diabetes, increases risk. If this is the mechanism through which obesity increases the risk of pancreatic cancer, then central adiposity may be a more relevant measure than BMI, despite the fact that it is likely to be measured less accurately. The relationship among central adiposity, glucose intolerance, and pancreatic cancer warrants further investigation.

Three previous cohort studies have also reported on height and the risk of pancreatic cancer: two found no evidence of an association (5, 20), whereas one found an association similar to that reported in the current study (RR, 1.81; 95% CI, 1.31-2.52 for top versus bottom category of height; ref. 6). Of the seven case-control studies that have also investigated this relationship (21-27), only two found evidence of an association between height and the risk of pancreatic cancer (21, 22). Adult height has also been found to be associated with an increased risk of some other cancers, including the breast, prostate, thyroid, colon, and endometrium (28, 29), and may be a proxy for exposure to growth and circulating growth factor levels during adolescence or childhood. However, as only 4 of the 11 epidemiologic studies that have reported on height and pancreatic cancer risk to date have found evidence of an association, and the fact that in the current study the significant trend was due to a reduced risk in the lowest quartile, rather than a consistently increasing risk across quartile, it remains unclear whether there is a real relationship between height and the risk of pancreatic cancer.

Most of the previous studies of pancreatic cancer and anthropometric factors have had to rely on self-reported measurements, which can result in bias due to the fact that weight tends to be underreported by overweight and obese people (30). A strength of the current study, therefore, is that in the majority of centers anthropometric factors were measured rather than self-reported. Measurement rather than self-reporting is particularly important for waist and hip circumferences, which are likely to be reported less accurately than height and weight. Differences between the centers in measurement methods may have resulted in some additional variability in weight, hip, and waist circumference measurements. Attempts were made to correct for these differences, but these adjustments were only possible on a center not an individual basis.

Four prospective studies and one retrospective study have previously investigated physical activity, and three of them have found some evidence that higher levels of physical activity are associated with a decreased risk of pancreatic cancer (5, 6, 31), whereas two of the previous prospective studies did not find any evidence of such an association (32, 33). There was no evidence in the current study that level of physical activity was related to the risk of developing pancreatic cancer. However, there were some differences between centers with respect to the physical activity questionnaires and how the questions were interpreted, which may have introduced additional variability and could have obscured a weak association between physical activity and the risk of pancreatic cancer.

In this large European cohort study, we found evidence that increased central adiposity and possibly height were associated with an increased risk of developing pancreatic cancer. Future studies should consider including measurements of waist and hip circumference to further investigate the relationship between control adiposity and the risk of developing this fatal disease.


   Acknowledgments
 
We thank all the participants in the European Prospective Investigation into Cancer and Nutrition.


   Footnotes
 
Grant support: Europe Against Cancer Programme of the European Commission (SANCO); Deutsche Krebshilfe; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund of the Spanish Ministry of Health; the Spanish Regional Governments of Andalucia, Asturia, Basque Country, Murcia and Navarra; The ISCIII Red de Centro RCESP grant C03/09; Cancer Research UK; Medical Research Council, United Kingdom; the Stroke Association, United Kingdom; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; the Wellcome Trust, United Kingdom; Greek Ministry of Health; Greek Ministry of Education; Associazione Italiana per la Ricerca sul Cancro, Milan; Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports; National Cancer Registry and the Regional Cancer Registries Utrecht, Amsterdam, East and Maastricht of the Netherlands; World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Skåne, Sweden.

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 10/14/05; revised 2/ 8/06; accepted 3/ 1/06.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. IARC. WHO mortality database. Lyon: IARC; 2004.
  2. Michaud DC. Epidemiology of pancreatic cancer. Minerva Chir 2004;59:99–111.[Medline]
  3. Huxley R, Moghaddam AA, Berrington de González A, Barzi F, Woodward M. Type-2 diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005;92:2076–83.[CrossRef][Medline]
  4. Calle EE, Rodriguez 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]
  5. 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]
  6. Michaud DS, Giovannucci E, Willett WC, Stampfer MJ, Fuchs CS. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 2001;286:921–9.[Abstract/Free Full Text]
  7. 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]
  8. 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.[CrossRef][Medline]
  9. Haftenberger M, Lahmann PH, Panico S, et al. Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr 2002;5:1147–62.[CrossRef][Medline]
  10. Haftenberger M, Schuit AJ, Tormo MJ, et al. Physical activity of subjects aged 50–64 years involved in the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr 2002;5:1163–76.[CrossRef][Medline]
  11. Cox DR. Analysis of binary data. London: Chapman and Hall Ltd.; 1977.
  12. Berrington de González A, Sweetland S, Spencer E. Meta-analysis of obesity and the risk of pancreatic cancer. Br J Cancer 2003;89:519–23.[CrossRef][Medline]
  13. Larsson SC, Permert J, Håkansson N, Naslund I, Bergkvist L, Wolf A. Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts. Br J Cancer 2005;93:1310–5.[CrossRef][Medline]
  14. Patel AV, Rodriguez C, Bernstein L, Chao A, Thun MJ, Calle E. Obesity, recreational physical activity, and risk of pancreatic cancer in a large U.S. Cohort. Cancer Epidemiol Biomarkers Prev 2005;14:459–66.[Abstract/Free Full Text]
  15. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005;293:194–202.[Abstract/Free Full Text]
  16. Stolzenberg-Solomon RZ, Graubard BL, Chari S, et al. Insulin, glucose and insulin resistance, and pancreatic cancer in male smokers. JAMA 2005;294:2872–8.[Abstract/Free Full Text]
  17. Carey VJ, Walters EE, Colditz GA, et al. Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses' Health Study. Am J Epidemiol 1997;145:614–9.[Abstract/Free Full Text]
  18. Wahrenberg H, Hertel K, Leijonhufvud B-M, Persson LG, Toft E, Amer P. Use of waist circumference to predict insulin resistance: retrospective study. BMJ 2005;330:1363–4.[Free Full Text]
  19. Bjorntorp P. Metabolic implications of body fat distribution. Diabetes Care 1991;14:1132–43.[Abstract]
  20. Friedman GD, van den Eeden SK. Risk factors for pancreatic cancer: an exploratory study. Int J Epidemiol 1993;22:30–7.[Abstract/Free Full Text]
  21. Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, Walter AM. Anthropometric and reproductive variables and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands. Int J Cancer 1992;52:24–9.[Medline]
  22. Ji BT, Hatch MC, Chow WH, et al. Anthropometric and reproductive factors and the risk of pancreatic cancer: a case-control study in Shanghai, China. Int J Cancer 1996;66:432–7.[CrossRef][Medline]
  23. Ghadirian P, Simard A, Baillargeon J, Maisonneuve P, Boyle P. Nutritional factors and pancreatic cancer in the Francophone community in Montreal, Canada. Int J Cancer 1991;47:1–6.[Medline]
  24. Howe GR, Jain M, Miller AB. Dietary factors and risk of pancreatic cancer: results of a Canadian population-based case-control study. Int J Cancer 1990;45:604–8.[Medline]
  25. Kalapothaki V, Tzonou A, Hseih CC, Toupadaki N, Karakatsani A, Trichopoulos D. Tobacco, ethanol, coffee, pancreatitis, diabetes mellitus, and cholelithiasis as risk factors for pancreatic carcinoma. Cancer Causes Control 1993;4:375–82.[CrossRef][Medline]
  26. Wynder EL, Dieck GS, Hall NE. Case-control study of decaffeinated coffee consumption and pancreatic cancer. Cancer Res 1984;46:5360–3.
  27. Zatonski W, Przewozniak K, Howe GR, Maisonneuve P, Walker AM, Boyle P. Nutritional factors and pancreatic cancer: a case-control study from south-west Poland. Int J Cancer 1991;48:390–4.[Medline]
  28. Gunnell D, Okasha M, Smith GD, Oliver SE, Sandhu J, Holly JM. Height, leg length, and cancer risk: a systematic review. Epidemiol Rev 1904;23:313–42.
  29. Okasha M, Gunnell D, Holly J, Davey Smith G. Childhood growth and adult cancer. Best Pract Res Clin Endocrinol Metab JID - 101120682 2002;16:225–41.
  30. 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.[CrossRef][Medline]
  31. Hanley AJ, Johnson KC, Villeneuve PJ, Mao Y; Canadian Cancer Registries Epidemiology Research Group. 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]
  32. Lee IM, Sesso HD, Oguma Y, Paffenbarger RS, Jr. Physical activity, body weight, and pancreatic cancer mortality. Br J Cancer 2003;88:679–83.[CrossRef][Medline]
  33. Sinner PJ, Schimtz KH, Anderson KE, Folsom AR. Lack of association of physical activity and obesity with incident pancreatic cancer in elderly women. Cancer Epidemiol Biomarkers Prev 2005;14:1571–3.[Free Full Text]



This article has been cited by other articles:


Home page
 JAMAHome page
D. Li, J. S. Morris, J. Liu, M. M. Hassan, R. S. Day, M. L. Bondy, and J. L. Abbruzzese
Body Mass Index and Risk, Age of Onset, and Survival in Patients With Pancreatic Cancer
JAMA, June 24, 2009; 301(24): 2553 - 2562.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
R. Z. Stolzenberg-Solomon, S. Weinstein, M. Pollak, Y. Tao, P. R. Taylor, J. Virtamo, and D. Albanes
Prediagnostic Adiponectin Concentrations and Pancreatic Cancer Risk in Male Smokers
Am. J. Epidemiol., November 1, 2008; 168(9): 1047 - 1055.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
Y. Bao and D. S. Michaud
Physical Activity and Pancreatic Cancer Risk: A Systematic Review
Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2671 - 2682.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
R. Z. Stolzenberg-Solomon, K. Adams, M. Leitzmann, C. Schairer, D. S. Michaud, A. Hollenbeck, A. Schatzkin, and D. T. Silverman
Adiposity, Physical Activity, and Pancreatic Cancer in the National Institutes of Health-AARP Diet and Health Cohort
Am. J. Epidemiol., March 1, 2008; 167(5): 586 - 597.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
D. S. Michaud, B. Wolpin, E. Giovannucci, S. Liu, B. Cochrane, J. E. Manson, M. N. Pollak, J. Ma, and C. S. Fuchs
Prediagnostic Plasma C-Peptide and Pancreatic Cancer Risk in Men and Women
Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2101 - 2109.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
B. A.J. Verhage, L. J. Schouten, R. A. Goldbohm, and P. A. van den Brandt
Anthropometry and Pancreatic Cancer Risk: An Illustration of the Importance of Microscopic Verification
Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1449 - 1454.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
A. Ansary-Moghaddam, R. Huxley, F. Barzi, C. Lawes, T. Ohkubo, X. Fang, S. H. Jee, M. Woodward, and Asia Pacific Cohort Studies Collaboration
The Effect of Modifiable Risk Factors on Pancreatic Cancer Mortality in Populations of the Asia-Pacific Region
Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2435 - 2440.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Berrington de González, A.
Right arrow Articles by Riboli, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berrington de González, A.
Right arrow Articles by Riboli, E.

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 Meeting Abstracts Online