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Investigating Physical Activity in the Etiology of Pancreatic Cancer: The Age at Which This Is Measured Is Important and Is Independent of Body Mass Index
Abstract
Objectives:
There are plausible biological mechanisms for how increased physical activity (PA) may prevent pancreatic cancer, although findings from epidemiological studies are inconsistent. We investigated whether the risk is dependent on the age at which PA is measured and if independent of body mass index (BMI).
Methods:
A total of 23,639 participants, aged 40 to 74 years, were recruited into the EPIC-Norfolk (European Prospective Investigation of Cancer) cohort study between 1993 and 1997 and completed validated questionnaires on PA. The cohort was monitored for pancreatic cancer development, and hazard ratios (HRs) were estimated and adjusted for covariates.
Results:
Within 17 years, 88 participants developed pancreatic cancer (55% female). There was no association between PA and risk in the cohort (HR trend, 1.06; 95% confidence interval [CI], 0.86-1.29). However, in participants younger than 60 years, higher PA was associated with decreased risk (highest vs lowest category HR, 0.27; 95% CI, 0.07-0.99). Higher PA was not inversely associated when older than 60 years (HR trend, 1.23; 95% CI, 0.96-1.57). Including BMI in all models produced similar estimates.
Conclusions:
The reasons why PA in younger, but not older, people may prevent pancreatic cancer need to be investigated. Physical activity may operate through mechanisms independent of BMI. If this association is causal, 1 in 6 cases might be prevented by encouraging more PA.
... R egular engagement in leisure-time physical activity (LTPA) is considered to have a protective effect against cancer among the general population. 1 In light of the aging of the population, there is a growing interest in whether this protective effect of LTPA equally applies to older age groups, characterized by decreased levels of physical activity 2 and increased cancer incidence. 3 Few previous cohort studies have focused specifically on adults aged 65 years or older, [4][5][6][7][8] while others have reported an overall risk for both middle-aged and old adults [9][10][11][12][13][14][15][16] or considered the older age groups separately in their analyses, [17][18][19] including several meta-analyses. [20][21][22][23][24] Findings of these studies support an inverse association between LTPA and cancer of the lung, 11,12,21 colon and rectum, 13 endometrium, 23 and breast 5,6,15,24 (although lack of association with breast cancer was also reported 14 ), whereas no evidence was observed for ovarian, 9 prostate, 20 or pancreatic 10,17,22 cancers (Supplemental Table 1, available online at http://www.mcpiqojournal.org). ...
... 3 Few previous cohort studies have focused specifically on adults aged 65 years or older, [4][5][6][7][8] while others have reported an overall risk for both middle-aged and old adults [9][10][11][12][13][14][15][16] or considered the older age groups separately in their analyses, [17][18][19] including several meta-analyses. [20][21][22][23][24] Findings of these studies support an inverse association between LTPA and cancer of the lung, 11,12,21 colon and rectum, 13 endometrium, 23 and breast 5,6,15,24 (although lack of association with breast cancer was also reported 14 ), whereas no evidence was observed for ovarian, 9 prostate, 20 or pancreatic 10,17,22 cancers (Supplemental Table 1, available online at http://www.mcpiqojournal.org). Although consistent with findings from the general population, 1 for older adults, some uncertainties still remain regarding the nature of this association. ...
Objective
To examine the association between leisure-time physical activity (LTPA) and long-term cancer risk in a nationwide cohort of older adults.
Participants and Methods
The cohort comprised participants of a national survey conducted between July 2005 and December 2006, constituting a random sample of Israeli community-dwelling adults aged 65 years or older. Based on self-reported LTPA habits, participants were classified as sufficiently active, insufficiently active, or inactive according to published guidelines. Cancer diagnosis was assessed via the Israeli National Cancer Registry through September 2015. Inverse probability weighted hazard ratios for incident cancer, based on propensity score, were estimated for LTPA categories.
Results
Analysis included 1542 participants with no history of cancer at baseline (median [25th-75th percentile] age, 73 years [69-78 years]; 826 [53.6%] women). Inactive participants (n=641 [41.6%]) were more likely to be female, of lower socioeconomic status, and with higher body mass index and poorer perceived health compared with their insufficiently active (n=443 [28.7%]) and sufficiently active (n=458 [29.7%]) counterparts. In the propensity score–weighted synthetic sample, the distribution of measured baseline covariates was similar across LTPA categories. Over a median follow-up of 9 years, 254 new cancer cases (16.5%) were diagnosed. Leisure-time physical activity was inversely associated with incident cancer, with adjusted hazard ratios (95% CIs) of 0.66 (0.46-0.93) in insufficiently active and 0.59 (0.42-0.82) in sufficiently active participants compared with inactive individuals (P value for trend = .002).
Conclusion
Among older adults, engaging in LTPA, even at lower levels than officially recommended, may have a beneficial effect on primary prevention of cancer.
... Pancreatic cancer incidence shows geographical variation which is similar to prostate, breast and colon cancer incidence pattern, with the highest incidence in North America, Europe, some countries of South America and the lowest incidence in Asia and Africa [19]. Approximately 250 000 cases die due to pancreatic cancer each year [52]. Pancreatic cancer often occurs at older ages and is diagnosed in late stages [10,50]. ...
... The 1-year survival rate of pancreatic cancer is 26% and the 5-years survival rate is 7% [50,53]. Smoking is the most important risk factor for pancreatic cancer [53], moreover high body mass index, low physical activity, age, some infectious agents such as Helicobacter pylori and hepatitis virus, chronic pancreatitis, cholecystectomy, chemical exposure, family history, insulin resistance, hyperglycemia, obesity and inappropriate dietary habits are associated with an increased risk of pancreatic cancer [9,14,51,52,[54][55][56][57]. Studies demonstrated that physical activity offers a protective effect against pancreatic cancer development [19,50,54,58]. ...
Introduction: Western lifestyle characterized by increased consumption of red meat, fat, processed food, smoking, alcohol drinking, lower consumption of vegetables and physical inactivity has been associated with a higher gastrointestinal cancer risk. Digestive system cancers are diagnosed at late stages when they show poor response to treatment and are associated with a high mortality rate. Colorectal, gastric, esophageal and pancreatic cancers are among the most common cancers worldwide. Studies show that more than 50% of gastrointestinal cancers develop as a result of inappropriate lifestyle. An inverse association between physical activity and many chronic diseases has been proved so far. However, the association between physical activity and some gastrointestinal cancers is still controversial. This study was aimed to determine the association between physical activity and gastrointestinal cancers risk.
Methods: We conducted a comprehensive search of English and Persian databases from February 2007 till December 2017, for studies investigating the association of physical activity and risk of gastrointestinal cancers. Finally, after reading full text of articles, 123 studies were included.
Results: Physical activity can be helpful in reducing the risk of gastrointestinal cancer, especially colon and pancreatic cancers. The risk reduction is not similar for different types of gastrointestinal cancers and also among males and females.
Conclusion: Different types of physical activity are associated with a lower risk of gastrointestinal cancer. However, it is unknown which type and intensity of physical activity are associated with a protective effect against gastro-intestinal cancer.
... Studies have shown that higher levels of physical activity can reduce the risk of developing PC. 3,4 Therefore, it can be inferred that leading a sedentary lifestyle may elevate the likelihood of developing PC. In developed nations, the occurrence of PC is observed to be three to four times greater when juxtaposed with its incidence in developing and underdeveloped countries. ...
Background
Pancreatic cancer (PC) stands out as one of the most formidable malignancies and exhibits an exceptionally unfavorable clinical prognosis due to the absence of well‐defined diagnostic indicators and its tendency to develop resistance to therapeutic interventions. The primary objective of this present study was to identify extracellular matrix (ECM)‐related hub genes (HGs) and their corresponding molecular signatures, with the intent of potentially utilizing them as biomarkers for diagnostic, prognostic, and therapeutic applications.
Methods
Three microarray datasets were sourced from the NCBI database to acquire upregulated differentially expressed genes (DEGs), while MatrisomeDB was employed for filtering ECM‐related genes. Subsequently, a protein–protein interaction (PPI) network was established using the STRING database. The created network was visually inspected through Cytoscape, and HGs were identified using the CytoHubba plugin tool. Furthermore, enrichment analysis, expression pattern analysis, clinicopathological correlation, survival analysis, immune cell infiltration analysis, and examination of chemical compounds were carried out using Enrichr, GEPIA2, ULCAN, Kaplan Meier plotter, TIMER2.0, and CTD web platforms, respectively. The diagnostic and prognostic significance of HGs was evaluated through the ROC curve analysis.
Results
Ten genes associated with ECM functions were identified as HGs among 131 DEGs obtained from microarray datasets. Notably, the expression of these HGs exhibited significantly (p < 0.05) higher in PC, demonstrating a clear association with tumor advancement. Remarkably, higher expression levels of these HGs were inversely correlated with the likelihood of patient survival. Moreover, ROC curve analysis revealed that identified HGs are promising biomarkers for both diagnostic (AUC > 0.75) and prognostic (AUC > 0.64) purposes. Furthermore, we observed a positive correlation between immune cell infiltration and the expression of most HGs. Lastly, our study identified nine compounds with significant interaction profiles that could potentially act as effective chemical agents targeting the identified HGs.
Conclusion
Taken together, our findings suggest that COL1A1, KRT19, MMP1, COL11A1, SDC1, ITGA2, COL1A2, POSTN, FN1, and COL5A1 hold promise as innovative biomarkers for both the diagnosis and prognosis of PC, and they present as prospective targets for therapeutic interventions aimed at impeding the progression PC.
... Physical activity may lead to a reduced risk of PDAC indirectly by reducing BMI, but also as an independent factor [81]. In a prospective study in participants younger than 60 years, higher physical activity was associated with decreased PDAC risk (highest vs. lowest category HR = 0.27, 95% CI = 0.07-0.99). ...
This study aims to summarize the modifiable risk factors for pancreatic ductal adenocarcinoma (PDAC) that have been known for a long time, as well as information from the most recent reports. As a cancer with a late diagnosis and poor prognosis, accurate analysis of PDAC risk factors is warranted. The incidence of this cancer continues to rise, and the five-year survival rate is the lowest with respect to other tumors. The influence of cigarette smoking, alcohol consumption, and chronic pancreatitis in increasing the risk of pancreatic ductal adenocarcinoma is continually being confirmed. There are also newly emerging reports relating to the impact of lifestyle, including physical activity, the gut and oral microbiome, and hepatotropic viruses. A precise understanding of PDAC risk factors can help to identify groups of high-risk patients, and this may contribute to population awareness and education as well as earlier diagnoses with possible better treatment outcomes.
... However, the role of physical activity (PA) remains unclear. A recent cohort study reported a decreased risk of PCa was associated with high PA, but only in individuals older than 60 years [218]. ...
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals’ risk for PCa.
... but not among those older than 60-years (HR = 1.23, 95% CI: 0.96-1.57) [43]. A study analyzed data from two cohort studies in China and reported a reduced pancreatic cancer risk associated with physical activities among men (HR = 0.71, 95% CI: 0.50-1.00) ...
Despite the advancement in medical knowledge that has improved the survival rate of many cancers, the survival rate of pancreatic cancer has remained dismal with a five-year survival rate of only 9%. The poor survival of pancreatic cancer emphasizes the urgent need to identify the causes or the risk factors of pancreatic cancer in order to establish effective preventive strategies. This review summarizes the current evidence regarding the environmental (non-genetic, including lifestyle, and clinical factors) risk factors of pancreatic cancer. Based on the current evidence, the established risk factors of pancreatic cancer are cigarette smoking, chronic diabetes, and obesity. Other strong risk factors include low consumption of fruits and vegetables, excess consumption of alcohol, poor oral hygiene, and the lack of allergy history. In the future, more studies are needed to identify additional risk factors of pancreatic cancer, especially the modifiable risk factors that could be included in a public health campaign to educate the public in order to reduce the incidence of pancreatic cancer.
... The updated literature search identified two cohort studies of physical activity and ovarian cancer; one found no association between physical activity and reduced risk for ovarian cancer (40), and one suggested increased risk for ovarian cancer with high physical activity levels (41). Two publications presented results of cohort studies that examined the association between physical activity and risk of pancreatic cancer: one found a negative association in men but not women (42), whereas the other found a negative association in persons younger than 60 yr but not in older individuals (43). ...
Purpose:
This article reviews and updates the evidence on the associations between physical activity and risk for cancer, and for mortality in persons with cancer, as presented in the 2018 Physical Activity Guidelines Advisory Committee Scientific Report.
Methods:
Systematic reviews of meta-analyses, systematic reviews, and pooled analyses were conducted through December 2016. An updated systematic review of such reports plus original research through February 2018 was conducted. This article also identifies future research needs.
Results:
In reviewing 45 reports comprising hundreds of epidemiologic studies with several million study participants, the report found strong evidence for an association between highest versus lowest physical activity levels and reduced risks of bladder, breast, colon, endometrial, esophageal adenocarcinoma, renal, and gastric cancers. Relative risk reductions ranged from approximately 10% to 20%. Based on 18 systematic reviews and meta-analyses, the report also found moderate or limited associations between greater amounts of physical activity and decreased all-cause and cancer-specific mortality in individuals with a diagnosis of breast, colorectal, or prostate cancer, with relative risk reductions ranging almost up to 40% to 50%. The updated search, with five meta-analyses and 25 source articles reviewed, confirmed these findings.
Conclusions:
Levels of physical activity recommended in the 2018 Guidelines are associated with reduced risk and improved survival for several cancers. More research is needed to determine the associations between physical activity and incidence for less common cancers and associations with survival for other cancers. Future studies of cancer incidence and mortality should consider these associations for population subgroups, to determine dose-response relationships between physical activity and cancer risk and prognosis, and to establish mechanisms to explain these associations.
The prevalence of obesity, diabetes mellitus (DM), and pancreatic cancer (PC) has been consistently increasing in the last two decades worldwide. Sharing various influential risk factors in genetics and environmental inducers in pathogenesis, the close correlations of these three diseases have been demonstrated in plenty of clinical studies using multiple parameters among different populations. On the contrary, most measures aimed to manage and treat obesity and DM effectively reduce the risk and prevent PC occurrence, yet certain drugs can inversely promote pancreatic carcinogenesis instead. Most importantly, an elevation of blood glucose with or without a reduction in body weight, along with other potential tools, may provide valuable clues for detecting PC at an early stage in patients with obesity and DM, favoring a timely intervention and prolonging survival. Herein, the epidemiological and etiological correlations among these three diseases and the supporting clinical evidence of their connections are first summarized to favor a better and more thorough understanding of obesity- and DM-related pancreatic carcinogenesis. After comparing the distinct impacts of different weight-lowering and anti-diabetic treatments on the risk of PC, the possible diagnostic implications of hyperglycemia and weight loss in PC screening are also addressed in detail.
Eine große Anzahl epidemiologische Studien zeigt, dass regelmäßige körperliche Bewegung das Erkrankungsrisiko für verschiedene gastrointestinale Tumorerkrankungen senken kann. Das Ausmaß der relativen Risikoreduktion liegt dabei zwischen 0 bis 21 %. Absolut gesehen lassen sich beispielsweise geschätzte 11,3 % aller Darmkrebsfälle in Deutschland auf einen Mangel an hinreichender Bewegung zurückführen. Plausible biologische Mechanismen können diese Beobachtung erklären. Damit weist körperliche Bewegung als veränderbarer Lebensstilfaktor ein substanzielles Potenzial für die bevölkerungsbezogene Krebsprävention von gastrointestinalen Erkrankungen auf. Gegenwärtige Empfehlungen legen nahe, täglich mindestens 30 bis 60 min moderat körperlich aktiv zu sein.
Due to improvements in the number of cancer survivors and survival time, there is a growing interest in healthy behaviors, such as physical activity (PA), and their potential impact on cancer- and non-cancer-related morbidity in individuals with cancer. Commissioned by the Spanish Society of Medical Oncology (SEOM), in this review, we sought to distill the most recent evidence on this topic, focusing on the mechanisms that underpin the effects of PA on cancer, the role of PA in cancer prevention and in the prognosis of cancer and practical recommendations for clinicians regarding PA counseling. Despite the available information, the introduction of exercise programs into the global management of cancer patients remains a challenge with several areas of uncertainty. Among others, the most effective behavioral interventions to achieve long-term changes in a patient’s lifestyle and the optimal intensity and duration of PA should be defined with more precision in future studies.
Objective:
Carcinogens in meat may be involved in pancreatic carcinogenesis. Meat intake was investigated using 7-day food diaries and according to factors potentially influencing carcinogenesis: age, cooking method, and antioxidants.
Methods:
Twenty-three thousand one hundred thirty-three participants in the European Prospective Investigation of Cancer-Norfolk cohort study completed 7-day food diaries and were followed up. Meat intakes were compared with controls and hazard ratios (HRs) calculated.
Results:
Eighty-six participants developed pancreatic cancer. If younger than 60 years at recruitment, all quintiles of red meat (Q1 vs Q5; HR, 4.62; 95% confidence interval [CI], 0.96-22.30; P = 0.06) and processed meat (Q1 vs Q5; HR, 3.73; 95% CI, 0.95-14.66; P = 0.06) were nonsignificantly positively associated, with significant trends across quintiles (HRtrend, 1.33; 95% CI, 1.01-1.77 and HRtrend, 1.37; 95% CI, 1.04-1.82, respectively). Red meat's effect was attenuated by higher, but not lower, plasma vitamin C (HR, 1.06; 95% CI, 0.69-1.63 vs HR, 1.84; 95% CI, 1.09-3.14) and for processed meat (HR, 1.07; 95% CI, 0.71-1.63 vs HR, 1.80; 95% CI, 1.10-2.96). A nonstatistically significant risk was observed for high-temperature cooking methods in younger people (HR, 4.68; 95% CI, 0.63-34.70; P = 0.13).
Conclusions:
Red and processed meats may be involved in pancreatic carcinogenesis.
Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations. Connective tissue growth factor (CTGF) gene is an interesting T2DM candidate gene in this chromosome region. CTGF is a key mediator of progressive pancreatic fibrosis up-regulated in type 2 diabetes. In contrast, CTGF inactivation in mice compromises islet cell proliferation during embryogenesis. The aim of our study was to investigate an impact of CTGF genetic variation on pancreatic beta-cell function and T2DM pathogenesis. We studied the effect of a common CTGF polymorphism rs9493150 on the risk of the T2DM development in three independent German cohorts. Specifically, the association between CTGF polymorphism and non-invasive markers of beta-cell area derived from oral glucose tolerance test was studied in subjects without diabetes. Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) study ( n = 1026) (OR = 0.637, CI (0.387–1.050); p = 0.077) nor in the European Prospective Investigation into Cancer and Nutrition-Potsdam (EPIC-Potsdam) ( n = 3049) cohort (RR = 0.77 CI (0.49–1.20), p = 0.249 for the recessive homozygote in general model), a significant association with increased diabetes risk was observed. The risk allele of rs9493150 had also no effect on markers of beta-cell area in the combined analysis of the MESYBEPO and Tübingen Family Study ( n = 1826). In conclusion, the polymorphism rs9493150 in the 5’-untranslated region of the CTGF gene has no association with T2DM risk and surrogate markers of beta-cell area.
Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity-cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment and increased cancer-related mortality. Biological mechanisms underlying the relationship between obesity and cancer are not well understood. They include modulation of energy balance and calorie restriction, growth factors, multiple signaling pathways, and inflammatory processes. Key among the signaling pathways linking obesity and cancer is the PI3K/Akt/mTOR cascade, which is a target of many of the obesity-associated factors and regulates cell proliferation and survival. Understanding the molecular and cellular mechanisms of the obesity-cancer connection is important in developing potential therapeutics. The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer.
Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations. Connective tissue growth factor (CTGF) gene is an interesting T2DM candidate gene in this chromosome region. CTGF is a key mediator of progressive pancreatic fibrosis up-regulated in type 2 diabetes. In contrast, CTGF inactivation in mice compromises islet cell proliferation during embryogenesis. The aim of our study was to investigate an impact of CTGF genetic variation on pancreatic beta-cell function and T2DM pathogenesis. We studied the effect of a common CTGF polymorphism rs9493150 on the risk of the T2DM development in three independent German cohorts. Specifically, the association between CTGF polymorphism and non-invasive markers of beta-cell area derived from oral glucose tolerance test was studied in subjects without diabetes. Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) study (n=1026) (OR=0.637, CI (0.387-1.050); p=0.077) nor in the European Prospective Investigation into Cancer and Nutrition-Potsdam (EPIC-Potsdam) (n=3049) cohort (RR=0.77 CI (0.49-1.20), p=0.249 for the recessive homozygote in general model), a significant association with increased diabetes risk was observed. The risk allele of rs9493150 had also no effect on markers of beta-cell area in the combined analysis of the MESYBEPO and Tübingen Family Study (n=1826). In conclusion, the polymorphism rs9493150 in the 5'-untranslated region of the CTGF gene has no association with T2DM risk and surrogate markers of beta-cell area.
Questions remain about the shape of the dose-response relationship between body mass index (BMI) and pancreatic cancer risk, possible confounding by smoking, and differences by gender or geographic location. Whether abdominal obesity increases risk is unclear.
We conducted a systematic review and meta-analysis of prospective studies of the association between BMI, abdominal fatness and pancreatic cancer risk and searched PubMed and several other databases up to January 2011. Summary relative risks (RRs) were calculated using a random-effects model.
Twenty-three prospective studies of BMI and pancreatic cancer risk with 9504 cases were included. The summary RR for a 5-unit increment was 1.10 [95% confidence interval (CI) 1.07-1.14, I(2) = 19%] and results were similar when stratified by gender and geographic location. There was evidence of a non-linear association, P(non-linearity) = 0.005; however, among nonsmokers, there was increased risk even within the 'normal' BMI range. The summary RR for a 10-cm increase in waist circumference was 1.11 (95% CI 1.05-1.18, I(2) = 0%) and for a 0.1-unit increment in waist-to-hip ratio was 1.19 (95% CI 1.09-1.31, I(2) = 11%).
Both general and abdominal fatness increases pancreatic cancer risk. Among nonsmokers, risk increases even among persons within the normal BMI range.
Most pancreatic neoplasms are classified as ductal adenocarcinoma because they show a ductal phenotype, making a ductal origin very likely. The duct lesions that may give rise to pancreatic ductal adenocarcinoma have been called pancreatic intraepithelial neoplasia (PanIN). A classification system for these lesions distinguishes between three grades of PanIN. Molecular studies revealed that PanIN-2 and PanIN-3 lesions represent a distinct step towards invasive carcinoma. While high-grade PanINs are extremely rare in the normal pancreas, low-grade PanINs are common in individuals older than 40 years and may be associated with lobular fibrosis and intraductal papillary mucinous neoplasms of the gastric type. This disease spectrum has also been described in members of kindreds with familial pancreatic cancer. The natural history and cause of PanINs are unknown. As PanIN-1 lesions entail little risk, while PanIN-3 lesions are high-risk lesions, it would be of interest to target PanIN-2 lesions, which can be regarded as the starting point of progressive neoplastic changes that lead to invasive pancreatic ductal adenocarcinoma. Global gene expression analysis identified several differentially expressed genes which show enhanced expression in PanINs and may be used as potential biomarkers to facilitate diagnosis and therapy.
To assess the validity and repeatability of a simple index designed to rank participants according to their energy expenditure estimated by self-report, by comparison with objectively measured energy expenditure assessed by heart-rate monitoring with individual calibration.
Energy expenditure was assessed over one year by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole-body calorimetry and doubly labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed a physical activity questionnaire that assessed past-year activity. A simple four-level physical activity index was derived by combining occupational physical activity together with time participating in cycling and other physical exercise (such as keep fit, aerobics, swimming and jogging).
One hundred and seventy-three randomly selected men and women aged 40 to 65 years.
The repeatability of the physical activity index was high (weighted kappa=0.6, ). There were positive associations between the physical activity index from the questionnaire and the objective measures of the ratio of daytime energy expenditure to resting metabolic rate and cardio-respiratory fitness As an indirect test of validity, there was a positive association between the physical activity index and the ratio of energy intake, assessed by 7-day food diaries, to predicted basal metabolic rate.
The summary index of physical activity derived from the questions used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study suggest it is useful for ranking participants in terms of their physical activity in large epidemiological studies. The index is simple and easy to comprehend, which may make it suitable for situations that require a concise, global index of activity.
Transforming growth factor-beta (TGF-beta) proteins regulate cell function, and have key roles in development and carcinogenesis. The intracellular effectors of TGF-beta signalling, the Smad proteins, are activated by receptors and translocate into the nucleus, where they regulate transcription. Although this pathway is inherently simple, combinatorial interactions in the heteromeric receptor and Smad complexes, receptor-interacting and Smad-interacting proteins, and cooperation with sequence-specific transcription factors allow substantial versatility and diversification of TGF-beta family responses. Other signalling pathways further regulate Smad activation and function. In addition, TGF-beta receptors activate Smad-independent pathways that not only regulate Smad signalling, but also allow Smad-independent TGF-beta responses.
Worldwide survival data for ductal adenocarcinoma of the pancreas are the lowest among the 60 most frequent types of organ cancers. Hence published data on long time survivors of this disease are controversial. We performed a nationwide study comprising all Finnish patients diagnosed with pancreatic cancer in the period 1990-1996 who survived for at least five years after diagnosis.
Data on patients registered as five year survivors of pancreatic cancer were obtained from the Finnish Cancer Registry and Statistics Finland. Slides or paraffin blocks were collected from patients recorded as having histologically proven pancreatic ductal adenocarcinoma (PDAC) and were re-evaluated in a double blind fashion by three pathologists with special expertise in pancreatic pathology.
Between 1990 and 1996, the Finnish Cancer Registry recorded 4922 pancreatic cancer patients, 89 of whom survived for at least five years. Reviewing this series of patients revealed 45 (49%) non-PDACs and 18 cases without histological verification. In 26 patients recorded as having histologically proven PDAC, re-evaluation of histological specimens confirmed PDAC in only 10 patients.
This study indicates that (1) the prognosis of PDAC remains poor and (2) careful histopathological review of all patients with pancreatic cancer is mandatory if survival data are to be meaningful.
Pancreatic cancer is the eighth major form of cancer-related death worldwide, causing 227 000 deaths annually. Type-II diabetes is widely considered to be associated with pancreatic cancer, but whether this represents a causal or consequential association is unclear. We conducted a meta-analysis to examine this association. A computer-based literature search from 1966 to 2005 yielded 17 case-control and 19 cohort or nested case-control studies with information on 9220 individuals with pancreatic cancer. The age and sex-adjusted odds ratio (OR) for pancreatic cancer associated with type-II diabetes was obtained from each study. The combined summary odds ratio was 1.82 (95% confidence interval (95% CI) 1.66-1.89), with evidence of heterogeneity across the studies (P=0.002 for case-control and P=0.05 for cohort studies) that was explained, in part, by higher risks being reported by smaller studies and studies that reported before 2000. Individuals in whom diabetes had only recently been diagnosed (< 4 years) had a 50% greater risk of the malignancy compared with individuals who had diabetes for > or =5 years (OR 2.1 vs 1.5; P=0.005). These results support a modest causal association between type-II diabetes and pancreatic cancer.
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 (P(trend) = 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; P(trend) = 0.02 and RR per 10 cm, 1.13; 95% CI, 1.01-1.26; P(trend) = 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/m(2)), 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.
Diabetes results from a deficiency of functional beta-cells. Previous studies have identified hepatocyte growth factor (HGF) and parathyroid hormone-related protein (PTHrP) as two potent beta-cell mitogens. The objective of this study is to determine 1) whether HGF and PTHrP have additive/synergistic effects on beta-cell growth and proliferation; 2) the signaling pathways through which these growth factors mediate beta-cell mitogenesis; and 3) whether activation of this/these signaling pathway(s) enhances human beta-cell replication.
We generated and phenotypically analyzed doubly transgenic mice overexpressing PTHrP and HGF in the beta-cell. INS-1 and primary mouse and human islet cells were used to identify mitogenic signaling pathways activated by HGF and/or PTHrP.
Combined overexpression of HGF and PTHrP in the beta-cell of doubly transgenic mice did not result in additive/synergistic effects on beta-cell growth and proliferation, suggesting potential cross-talk between signaling pathways activated by both growth factors. Examination of these signaling pathways in INS-1 cells revealed atypical protein kinase C (PKC) as a novel intracellular target activated by both HGF and PTHrP in beta-cells. Knockdown of PKC zeta, but not PKC iota/lambda, expression using specific small-interfering RNAs blocked growth factor-induced INS-1 cell proliferation. Furthermore, adenovirus-mediated delivery of kinase-dead PKC zeta completely inhibited beta-cell proliferation in primary islet cells overexpressing PTHrP and/or HGF. Finally, adenovirus-mediated delivery of constitutively active PKC zeta in mouse and human primary islet cells significantly enhanced beta-cell proliferation.
PKC zeta is essential for PTHrP- and HGF-induced beta-cell proliferation. PKC zeta activation could be useful in therapeutic strategies for expanding beta-cell mass in vitro and in vivo.
Several epidemiologic studies have examined the association between physical activity and pancreatic cancer risk; however, the results of these studies are not consistent.
This study examined the associations of total, moderate, and vigorous physical activity to pancreatic cancer in a cohort of 33,530 U.S. women enrolled in the Breast Cancer Detection Demonstration Project (BCDDP). At baseline (1987-1989), information on physical activity over the past year was obtained using a self-administered questionnaire. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals of pancreatic cancer risk.
70 incident cases of pancreatic cancer were ascertained during 284,639 person years of follow-up between 1987-1989 and 1995-1998. After adjustment for age, body mass index, smoking status, history of diabetes, and height, increased physical activity was related to a suggestively decreased risk of pancreatic cancer. The RRs for increasing quartiles of total physical activity were 1.0, 0.80, 0.66, 0.52 (95% CI = 0.26, 1.05; ptrend = 0.05). This association was consistent across subgroups defined by body mass index and smoking status. We also observed statistically non-significant reductions in pancreatic cancer risk for women in the highest quartile of moderate (RR = 0.57; 95% CI = 0.26, 1.26) and highest quartile of vigorous physical activity (RR = 0.63; 95% CI = 0.31, 1.28) compared to their least active counterparts.
Our study provides evidence for a role of physical activity in protecting against pancreatic cancer.
Can physical activity modulate pancreatic cancer risk? A systematic review and meta-analysis - Volume 68 Issue OCE3 - M. A. O'Rorke, M. M. Cantwell, C. R. Cardwell, H. G. Mullholland, L. J. Murray
Exercise is an effective treatment for type 2 diabetes mellitus, resulting in stabilization of plasma glucose in the acute phase and improvements in body composition, insulin resistance and glycosylated haemoglobin with chronic exercise training. However, the most appropriate exercise prescription for type 2 diabetes has not yet been established, resulting from insufficient evidence to determine the optimum type, intensity, duration or frequency of exercise training. Furthermore, patient engagement in exercise is suboptimal. There are many likely reasons for low engagement in exercise; one possible contributory factor may be a tendency for expert bodies to prioritize the roles of diet and medication over exercise in their treatment guidelines. Published treatment guidelines vary in their approach to exercise training, but most agencies suggest that people with type 2 diabetes engage in 150 min of moderate to vigorous aerobic exercise per week. This prescription is similar to the established guidelines for cardiovascular health in the general population. Future possibilities in this area include investigation of the physiological effects and practical benefits of exercise training of different intensities in type 2 diabetes, and the use of individualized prescription to maximize the health benefits of training.
Purpose:
Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan).
Methods:
The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer.
Results:
Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52).
Conclusions:
These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.
Objective:
To investigate whether the dietary antioxidants vitamins C and E, selenium and zinc decrease the risk of developing pancreatic cancer, for the first time using 7-day food diaries, the most accurate dietary methodology in prospective work.
Design:
23,658 participants, aged 40-74 years, recruited into the EPIC-Norfolk Study completed 7-day food diaries which recorded foods, brands and portion sizes. Nutrient intakes were calculated in those later diagnosed with pancreatic cancer and in 3970 controls, using a computer program with information on 11,000 foods. Vitamin C was measured in serum samples. The HRs of developing pancreatic cancer were estimated across quartiles of intake and thresholds of the lowest quartile (Q1) against a summation of the three highest (Q2-4).
Results:
Within 10 years, 49 participants (55% men), developed pancreatic cancer. Those eating a combination of the highest three quartiles of all of vitamins C and E and selenium had a decreased risk (HR=0.33, 95% CI 0.13 to 0.84, p<0.05). There were threshold effects (Q2-4 vs Q1) for selenium (HR=0.49, 95% CI 0.26 to 0.93, p<0.05) and vitamin E (HR=0.57, 95% CI 0.29 to 1.09, p<0.10). The HRs of quartiles for antioxidants, apart from zinc, were <1, but not statistically significant. For vitamin C, there was an inverse association with serum measurements (HR trend=0.67, 95% CI 0.49 to 0.91, p=0.01), but the threshold effect from diaries was not significant (HR=0.68, 95% CI 0.37 to 1.26).
Conclusion:
The results support measuring antioxidants in studies investigating the aetiology of pancreatic cancer. If the association is causal, 1 in 12 cancers might be prevented by avoiding the lowest intakes.
Risk factors for pancreatic cancer, other than smoking and diabetes, are not well-established, especially for women. In a cohort of 1.3 million middle-aged women, followed for 9.2 million person-years for cancer incidence and 11.5 million person-years for mortality, there were 1,338 incident pancreatic cancer cases and 1,710 deaths from the disease. Using proportional hazards models, we calculated adjusted relative risks (RRs) and 95% confidence intervals (CIs) by smoking, height, body mass index (BMI), alcohol consumption, physical activity and history of diabetes. Pancreatic cancer incidence was greater in current than never smokers (RR 2.39, CI 2.10–2.73), the risk increasing with the number of cigarettes smoked. The incidence of pancreatic cancer also increased with increasing BMI (RR 1.34, CI 1.13–1.57 for BMI ≥ 30 vs. 22.5–25 kg/m2), and with a history of diabetes (RR 1.58, CI 1.22–2.03, with vs. without such a history). These factors were also associated with increased mortality from pancreatic cancer. Height, alcohol consumption and physical activity showed little or no association with pancreatic cancer risk. © 2008 Wiley-Liss, Inc.
Diabetes mellitus (DM) is widely considered to be associated with risk of pancreatic cancer (PaC), however, whether DM is a cause or a consequence of PaC is still controversial. We examined this association by conducting a detailed meta-analysis of cohort studies.
Studies were identified by searching Medline and Embase through November 30, 2010. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model.
A total of thirty-five cohort studies were included in this meta-analysis. DM was associated with an increased risk of PaC (the summary RRs=1.94; 95% CI, 1.66-2.27), with significant evidence of heterogeneity among these studies (p<0.001, I²=93.6%). Subgroup analyses revealed that the increased risk of PaC was independent of geographic locations, sex, study design, alcohol consumption, body mass index (BMI) and smoking status. In addition, the relative risk of PaC was correlated negatively with the duration of DM, with the highest risk of PaC found among patients diagnosed within less than 1 year. There was no significant publication bias (p=0.136 for Egger's regression asymmetry test).
Findings from this meta-analysis strongly support that diabetes is associated with an increased risk of PaC in both males and females and that DM is both an early manifestation and an etiologic factor of pancreatic cancer.
The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21-22.9 kg/m(2) , pancreatic cancer risk was 47% higher (95%CI:23-75%) among obese (BMI ≥ 30 kg/m(2) ) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09-1.56 comparing BMI ≥ 25 kg/m(2) to a BMI between 21 and 22.9 kg/m(2) ). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m(2) ) and not obese at baseline (BMI < 30 kg/m(2) ), pancreatic cancer risk was 54% higher (95%CI = 24-93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≥ 10 kg/m(2) between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03-1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.
Over the last 60 years, Japanese people have experienced a rapid and drastic change in lifestyle, including diet. Suspicions have been raised that so-called ‘Westernization’, characterized by a high-calorie diet and physical inactivity, is associated with increasing trends in the incidence of cancer of the colon, liver, pancreas, prostate, and breast, as well as type 2 diabetes. Epidemiological evidence from our prospective study, the Japan Public Health Center-based Prospective (JPHC) study, and systematic literature reviews generally support the idea that factors related to diabetes or insulin resistance are associated with an increased risk of colon (mostly in men), liver, and pancreatic cancers. These cancers are inversely associated with physical activity and coffee consumption, which are known to decrease the risk of type 2 diabetes. The suggested mechanism of these effects is that insulin resistance and the resulting chronic hyperinsulinemia and increase in bioavailable insulin-like growth factor 1 (IGF1) stimulate tumor growth. In contrast, associations with diabetes are less clear for cancer of the colon in women, and breast and prostate, which are known to be related to sex hormones. The effect of insulin resistance or body fat on sex-hormone production and bioavailability may modify their carcinogenic effect differently from cancers of the colon in men, and liver and pancreas. In conclusion, there is substantial evidence to show that cancers of the colon, liver, and pancreas are associated with insulin resistance, and that these cancers can be prevented by increasing physical activity, and possibly coffee consumption.
(Cancer Sci 2010; 101: 1073–1079)
Numerous epidemiological studies have examined the association between physical activity and pancreatic cancer; however, findings from individual cohorts have largely not corroborated a protective effect. Among other plausible mechanisms, physical activity may reduce abdominal fat depots inducing metabolic improvements in glucose tolerance and insulin sensitivity, thereby potentially attenuating pancreatic cancer risk. We performed a systematic review to examine associations between physical activity and pancreatic cancer. Six electronic databases were searched from their inception through July 2009, including MEDLINE and EMBASE, seeking observational studies examining any physical activity measure with pancreatic cancer incidence/mortality as an outcome. A random effects model was used to pool individual effect estimates evaluating highest vs. lowest categories of activity. Twenty-eight studies were included. Pooled estimates indicated a reduction in pancreatic cancer risk with higher levels of total (five prospective studies, RR: 0.72, 95% CI: 0.52-0.99) and occupational activity (four prospective studies, RR: 0.75, 95% CI: 0.59-0.96). Nonsignificant inverse associations were seen between risks and recreational and transport physical activity. When examining exercise intensity, moderate activity appeared more protective (RR: 0.79, 95% CI: 0.52-1.20) than vigorous activity (RR: 0.97, 95% CI: 0.85-1.11), but results were not statistically significant and the former activity variable incorporated marked heterogeneity. Despite indications of an inverse relationship with higher levels of work and total activity, there was little evidence of such associations with recreational and other activity exposures.
Glucose is a cardinal secretory and mitogenic stimulus for the insulin-producing pancreatic beta-cell both in vitro and in vivo, but the mechanisms by which the sugar acts mitogenically remain largely elusive. In this study, the intracellular pathways that convey glucose-induced mitogenic and secretory signaling in beta-cells were investigated. For this purpose, fetal rat pancreatic islets enriched in beta-cells were cultured in 3.3 or 16.7 mmol/l glucose for 3 days. It was found that glucose stimulated beta-cell replication, insulin secretion, and cAMP content. These effects were mimicked by agonists of cAMP-dependent protein kinases but not by guanosine-3',5'-cyclic monophosphate (cGMP). Antagonists of cAMP-dependent protein kinases failed to block the glucose-induced increments in beta-cell replication and insulin secretion. Glucose is known to activate protein kinase C, and a protein kinase C-activating phorbol ester was found to promote beta-cell mitogenesis and insulin secretion. Conversely, when protein kinase C was inhibited, the mitogenic (but not secretory) response to glucose was attenuated. There were no additive or synergistic effects on beta-cell replication when cAMP and phorbol ester were combined, whereas insulin secretion was potentiated by this combination. Artificially causing Ca2+ inlet by glibenclamide or ionomycin did not result in a stimulated mitogenic response, and preventing Ca2+ influx by blocking plasma membrane Ca2+ channels did not abolish the mitogenicity of glucose, although it reduced insulin secretion. Pretreatment of islets with pertussis toxin, known to regulate transduction of signals through heterotrimeric GTP-binding proteins, completely prevented the stimulatory effect of glucose on beta-cell mitogenesis but not on insulin secretion. We conclude that specific activation of protein kinase C or cAMP synthesis is sufficient to increase beta-cell mitogenesis and insulin secretion, whereas cGMP appears not to affect these processes. However, cAMP does not seem to mediate the mitogenicity or secretory action of glucose. The results instead suggest that signaling through GTP-binding proteins and protein kinase C activation is required for transduction of the mitogenic, but not secretory, message of the sugar in the beta-cell.
Introduction: The prevalence and human health consequences of deficient and inadequate vitamin D status were assessed. Materials and methods: The assessment was performed through an evaluation of the extensive existing relevant scientific literature. A scientific literature search was conducted on MEDLINE (National Library of Medicine, Bethesda, MD, USA) for relevant articles regarding the prevalence and human health consequences of deficient and inadequate vitamin D status published prior to November, 2014. Additional publications were identified from references provided in original papers. Results: Several thousand relevant scientific publications were identified, examined, and evaluated. Of this pool of potential data, the information provided by 348 publications was incorporated into this assessment. Conclusions: Vitamin D deficiency and inadequacy are rampant worldwide. The many physiological functions that rely upon vitamin D justify a reassessment of the definition of vitamin D deficiency that reflects the true importance of this endocrinologically active vitamin to human health. The continuing preventable gobal epidemic of suboptimal vitamin D status challenges the relevance of current attitudes toward dietary supplementation with this critical nutrient.
To examine the association between several medical conditions, anthropometric measurements, occupational and leisure physical activity, and pancreatic cancer in a cohort of male Finnish smokers.
We performed a cohort analysis of the 172 subjects who developed pancreatic cancer between 1985 and 1997 (median 10.2 years follow-up) among the 29,048 male smokers, 50-69 years old, who had complete baseline data and participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI).
We observed positive associations between pancreatic cancer risk and self-reported history of diabetes mellitus (HR=2.02, 95% CI 1.17-3.50) and bronchial asthma (HR=2.16, 95% CI 1.17-3.98). Men having combined occupational and leisure activity greater than at sedentary levels had reduced risk for the cancer; for example those with moderate/heavy activity in both settings showed a HR of 0.42 (95% CI 0.22-0.83). There were no significant associations with other self-reported illnesses, total or HDL (high-density lipoprotein) cholesterol, height, weight, or body mass index.
Our data suggest that diabetes mellitus and bronchial asthma predict the subsequent risk of developing pancreatic cancer in male smokers, and that greater physical activity may reduce the risk.
To examine body mass index (BMI) and physical activity as risk factors for pancreatic cancer.
Eight-year prospective data from 77,255 men and 90,175 women including 237 and 235 pancreatic cancer cases, respectively, in the Hawaii-Los Angeles Multiethnic Cohort Study were analyzed. Participants completed a questionnaire that included questions on body weight, height, and physical activity. Cox proportional hazards models were calculated to estimate relative risks (RR) of pancreatic cancer by levels of BMI and total physical activity (as metabolic equivalents (METs)) adjusted for several potential confounders.
Obesity (BMI > or = 30 kg/m(2)) was associated with an increased pancreatic cancer risk in men (RR = 1.51 (95% CI: 1.02-2.26)), but a reduced risk in women (RR = 0.65 (95% CI: 0.43-0.99)). In men the risk was higher in never smokers than in current or former smokers, though differences were not statistically significant. Physical activity was not associated with pancreatic cancer risk in either men or women.
The findings suggest, that a BMI of > or = 30 kg/m(2) may be a risk factor for pancreatic cancer in men. No evidence of an effect of physical activity on risk was found.
The impact of total physical activity level on cancer risk has not been fully clarified, particularly in non-Western, relatively lean populations. The authors prospectively examined the association between daily total physical activity (using a metabolic equivalents/day score) and subsequent cancer risk in the Japan Public Health Center-based Prospective Study. A total of 79,771 general-population Japanese men and women aged 45-74 years who responded to a questionnaire in 1995-1999 were followed for total cancer incidence (4,334 cases) through 2004. Compared with subjects in the lowest quartile, increased daily physical activity was associated with a significantly decreased risk of cancer in both sexes. In men, hazard ratios for the second, third, and highest quartiles were 1.00 (95% confidence interval (CI): 0.90, 1.11), 0.96 (95% CI: 0.86, 1.07), and 0.87 (95% CI: 0.78, 0.96), respectively (p for trend = 0.005); in women, hazard ratios were 0.93 (95% CI: 0.82, 1.05), 0.84 (95% CI: 0.73, 0.96), and 0.84 (95% CI: 0.73, 0.97), respectively (p for trend = 0.007). The decreased risk was more clearly observed in women than in men, especially among the elderly and those who regularly engaged in leisure-time sports or physical exercise. By site, decreased risks were observed for cancers of the colon, liver, and pancreas in men and for cancer of the stomach in women. Increased daily physical activity may be beneficial in preventing cancer in a relatively lean population.
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