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Review paper

Pancreatic cancer trends in Europe: epidemiology and risk factors

Graeme Hawksworth
,
Jake Hales
,
Fransico Martinez
,
Allen Hynes
,
Angela Hamilton
,
Veronica Fernandez

Medical Studies/Studia Medyczne 2019; 35 (2): 164–171
Online publish date: 2019/06/28
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- Pancreatic cancer.pdf  [0.87 MB]
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Introduction

Based on the GLOBOCAN 2018 estimates by the International Agency for Research on Cancer (IARC), pancreatic cancer is the 12th most common cancer worldwide and the seventh most common cancer in Europe [1, 2]. With the incidence and mortality rates being very close, pancreatic cancer is considered one of the deadliest of all cancers. Rates of pancreatic cancer are 3–4 times higher in the developed world, particularly in Europe, North America, Australia, and New Zealand, despite the efforts and campaigns that aim at raising awareness in these countries to control the disease [3–5].
The most common type of pancreatic cancer is adenocarcinoma (tumour of the exocrine pancreas), which accounts for almost 85% of cases [6]. In most of the cases (around 75%) the cancer occurs at the head or neck of the pancreas, while 15–20% occur at the body, and only 5–10% at the tail of the pancreas.
The symptoms of pancreatic cancer are subtle, especially the body and tail tumours; therefore, the diagnosis of pancreatic cancer requires a physician with a high index of suspicion. Surgical resection is potentially curative in the very early stages of the disease [7]. However, most of the patients are diagnosed in the late stages of pancreatic cancer after metastasis has occurred [8]. Prognosis is generally very poor, with most patients dying 4–6 months after being diagnosed with the disease. Around 28% of the cases survive a year after being diagnosed, and the percentage declines to only 9% after 5 years.
The link between tobacco smoking and pancreatic cancer explains the variation in incidence between the different countries, as well as between sexes. Genetic predisposition, obesity, diabetes mellitus, and alcohol consumption are also important risk factors; however, the exact causes are not fully determined [6].
The number of deaths from pancreatic cancer is expected to be greater than the number due to breast cancer by 2025 [9]. Therefore, studying pancreatic cancer trends in Europe is important because it sheds light on the effectiveness of the measures previously taken by European countries to control pancreatic cancer. Also, the rising incidence and mortalities from pancreatic cancer should make us focus on formulating a plan to fight the disease in the future.

Epidemiology

Incidence

The estimated number of cases of pancreatic cancer worldwide in 2018 was 458,918, with a male to female ratio of 1 : 1.13. Among those 458,918 patients, 132,559 cases were found in Europe [1]. This indicates that around 29% of pancreatic cancer patients are found in such a small continent. Europe comes in second place regarding pancreatic cancer incidence (number of new patients), behind the Western Pacific region, and the estimated highest age-standardised incidence rates per 100,000 individuals exist in Europe (9.3 per 100,000 males and 6.3 per 100,000 females) [1]. Estimated incidence rates in each of the sexes separately, in the different world regions, showed that pancreatic cancer rates are highest among males in Central and Eastern Europe (9.9 per 100,000 men), namely Latvia and the Republic of Moldova, with a rate of 15.3 per 100,000 males in both countries [10]. The highest incidence rates among women were in Western Europe with a rate of 7.2 per 100,000 women. Hungary had the highest rate in Europe and was second highest globally regarding the incidence of pancreatic cancer among females (9.1 per 100,000), followed by Slovakia, Czech, and Serbia (all data extracted from GLOBOCAN 2018) [1].
Among European Union countries, Germany, France, and Italy, respectively, are the three counties with the highest numbers of pancreatic cancer patients (Figure 1). The incidence in Poland is 7.1 per 100,000 in 2018 [1]. The age of peak incidence is between 60 and 80 years of age.

Mortality

Pancreatic cancer resulted in 432,242 deaths worldwide in 2018, with 128,045 of them in Europe. This estimate shows that fatalities due to pancreatic cancer came in fourth place among fatalities from all cancers in Europe, following lung, colorectum, and breast [1, 6, 11, 12].
Mortality rates from pancreatic cancer in Europe in 2018 reached 8.8 per 100,000 males and 5.7 per 100,000 females. Corresponding with the incidence rates, mortality rates were most common among men in Central and Eastern Europe (7.9 per 100,000) and women in Western Europe (6.3 per 100,000). The Republic of Moldova had the most prominent mortality rates in Europe (Figure 2), while the Russian Federation had the highest total number of deaths from pancreatic cancer (226,910 men and 205,332 women) [1]. The mortality rate in Poland was 6.9 per 100,000 in 2018 [1].

Trends

In 2012, the number of patients diagnosed with pancreatic cancer worldwide, according to GLOBOCAN 2012, was 337,872, which means that the incidence increased by 121,046 patients in 6 years [13]. Recent advances in imaging and other diagnostic tools may have contributed to the apparent increase in pancreatic cancer incidence because more patients are diagnosed in the early stages of the disease [14]. This may have also affected the 5-year survival estimates.
Pancreatic cancer incidence and mortality in Europe were at their peak in the 1970s and 1980s in both men and women, and they markedly declined in the 1990s. Two studies showed this, one of which was conducted in England and Wales, and the other included 22 different European countries [15, 16]. Survival at 5 years has improved over time for patients with pancreatic cancer, worldwide. In 1975, the 5-year survival (regardless of the stage of the disease) was only 3%. While in 2006, the percentage increased to 7% [17]. Nowadays, 5-year survival has reached approximately 9%.
A retrospective observational study was published in 2013. It analysed data from different cancer registries across Europe and included more than 10 million patients with cancer from 1999 until 2007 [18]. The study stated that the average 5-year survival for pancreatic cancer was 6% in men and 8% in women in Europe. The relative 5-year survival was below average in the United Kingdom as compared to the rest of Europe. The percentage was 4% in men in England, Wales, and Scotland, and only 2% in Northern Ireland. In women, the average 5-year survival was 5% in England and 7% in Wales [18, 19].
The highest rate of 5-year survival in Europe was among men in Croatia (around 11%) and women in Belgium. (12%). Unlike many other cancers; such as prostate, breast, rectal cancer, and non-Hodgkin lymphoma, pancreatic cancer survival rates have not improved significantly over the past few decades in Europe [18]. By 2040 the estimated number of new pancreatic cancer cases in Europe is expected to reach 171,414 patients (Figure 3). Moreover, the number of deaths expected from pancreatic cancer is 168,489 [20]. The increasing numbers of pancreatic cancer cases are consistent with the demographic changes, while there is no anticipated change in the risk of developing the disease.
Pancreatic cancer survival is largely dependent on the patient’s age. Between 15 and 49 years of age, five-year survival rates were around 17% in men and 26% in women in England between 2009 and 2013. Survival rates were much lower in the other age groups [21]. Western Europe is expected to replace Central and Eastern Europe as the region with the highest number of new cases, as well as mortalities, from pancreatic cancer by 2040 [20, 22].

Risk factors

Several risk factors have been identified relating to pancreatic cancer development. Here we discuss the important risk factors that play a role in the pathogenesis and development of pancreatic cancer. Risk factors of pancreatic cancer are mainly classified into two types: modifiable and non-modifiable. Modifiable risk factors include alcohol, smoking, diet, obesity, and exposure to toxic chemicals or substances. Non-modifiable risk factors include age, gender, ethnicity, family history and genetic factors, diabetes mellitus, chronic infections, chronic pancreatitis, and non-O blood group. Here we discuss mainly the modifiable risk factors for pancreatic cancer because these influence the epidemiology of pancreatic cancer worldwide.

Smoking

Smoking is a significant risk factor for pancreatic cancer development, and it can account for about 20–25% of the cases of pancreatic cancer [23, 24]. Pooled studies have attributed 22% of the pancreatic cancer cases in the United Kingdom (UK) to smoking [25]. Data from the International Pancreatic Cancer Case-Control Consortium (Panc4) study has shown that the risk of pancreatic cancer in current smokers is 2.2 times and that of former smokers is 1.2 times compared to those who have never smoked [26]. The risk increases with the number of cigarettes smoked and the duration of smoking [27]. The European Prospective Investigation into Cancer and Nutrition (EPIC) study has shown that the risk of former smokers never approaches that of smokers after 5 years or more of quitting smoking [28]. Those who smoke cigars are at 1.6 times increased risk of pancreatic cancer compared to non-smokers [29]. While there was no significant association seen with smokeless tobacco, studies have been inconclusive [29, 30]. Studies have shown that the use of snus (moist powdered tobacco) in the Swedish population is not associated with pancreatic cancer risk [31].

Obesity and physical inactivity

Several studies have shown a link between pancreatic cancer risk and high body mass index (BMI) and physical inactivity [32–37]. Obesity and overweight are attributed to about 12% of pancreatic cancer cases in the UK [25]. Risk of pancreatic cancer increases by 10% for every 5-unit increase in BMI [33]. A 10-cm increase in waist circumference increases the risk for pancreatic cancer by 11%, and a 0.1 increase in waist-to-hip ratio increases the risk by 19% [33]. Studies have shown that regular leisure-time physical activity decreases the pancreatic cancer risk by 11% to 35% [38, 39]. Physical activity decreases the risk of pancreatic cancer especially in people who are overweight with a BMI of at least 25 kg/m2 [40]. Being obese or overweight during early adulthood increases the risk of pancreatic cancer onset at a younger age [41]. Higher levels of prediagnostic BMI levels are associated with decreased survival in pancreatic cancer, according to two large prospective clinical trials [42].

Alcohol

Based on multiple studies, high alcohol consumption (more than three drinks per day) undoubtedly increases the risk of pancreatic cancer, whereas for low-to-moderate alcohol intake there was no association found [43–45]. Cigarette smoking confounded the relationships between alcohol use and pancreatic cancer risk. Alcohol intake was associated with a two-fold increased risk of pancreatic cancer in current smokers [46]. A meta-analysis has shown that the risk of pancreatic cancer is 20% higher in those who consume > 50 γ of alcohol when compared to non-drinkers or occasional drinkers [47]. However, no increased risk of pancreatic cancer was seen in those who consume < 50 γ of alcohol per day in the same meta-analysis [47].

Diet

Studies evaluating the risk between diet and pancreatic cancer risk have been inconclusive; many studies have shown an increased risk, but not all studies. A meta-analysis of prospective studies has shown that red meat consumption of > 120 g/day was associated with an elevated risk of pancreatic cancer [48]. Other studies have shown that consumption of a high amount of red and processed meats and dietary fat of animal origin was associated with increased pancreatic cancer risk [48–50]. However, some other studies have not shown an association between diet and pancreatic cancer risk [51–53]. High intake of fruit and vegetables, especially those enriched in antioxidants and citrus, have a protective action [54]. Some studies have shown a decreased risk of pancreatic cancer with nut consumption [55]. A large cohort study in the UK has shown that pancreatic cancer mortality is lower with vegetarians, vegans, and low meat eaters when compared to regular meat eaters [56].

Occupational exposures

The fraction of pancreatic cancer within a population, which has been attributed to occupational exposure, is estimated at 12%. Studies have shown that exposure to nickel, cadmium, and arsenic was associated with increased pancreatic cancer risk [57–59]. Selenium, which is an essential micronutrient, has been shown in several studies to be inversely associated with several cancers, including pancreatic cancer [60, 61]. A study in Spain has shown an increased risk of pancreatic cancer with exposure to pesticides, aniline dyes, benzopyrene, diesel and gasoline exhaust, and hydrocarbon solvents [62].

Other risk factors

Approximately 5–10% of people with pancreatic cancer have a family history of pancreatic cancer [63]. Germline mutations of BRCA, CDKN2A, MLH1, ATM, and PALB2 genes have been linked to pancreatic cancer [64]. KRAS, p53, and SMAD4 are seen in inherited genetic mutations and are linked to increased pancreatic cancer risk [65, 66]. Studies have also shown that individuals with non-O blood group (type A, AB, or B) were significantly more likely to develop pancreatic cancer when compared to blood group O individuals, and the genome-wide association study confirmed this [67, 68]. Patients with cystic fibrosis are also at increased risk for pancreatic cancer [69]. Studies have shown that 1.8% of patients with chronic pancreatitis will develop pancreatic cancer within 10 years from the diagnosis, and 4% after 20 years [70].
The association between diabetes mellitus type I and II with pancreatic cancer has been reported in multiple studies [71–74], although some studies have shown that diabetes is a consequence of the tumour rather than it causing cancer [75, 76]. Studies have shown that existing chronic pancreatitis is a strong risk factor for pancreatic cancer [77, 78]. The risk reaches 1.8% at 10 years and 4% at 20 years after diagnosis of chronic pancreatitis [77, 79, 80]. The relationship with coffee consumption and pancreatic cancer risk has been controversial; some studies have shown an increased risk at higher levels of coffee consumption while some have not shown any relationship [81].
Some studies have shown an association between Helicobacter pylori infection and increased pancreatic cancer risk, although this has been controversial [82]. Some studies have also shown an association between hepatitis B and hepatitis C infection and increased pancreatic cancer [83–85].

Conclusions

The incidence of pancreatic cancer in Europe is considerably higher when compared to other continents. In Europe, pancreatic cancer is the ninth most common cancer and the fourth most deadly cancer. With incidence and mortality rates being very close together, pancreatic cancer is considered one of the deadliest of all cancers. Lifestyle in developed nations, including the rise in physical inactivity and obesity, tobacco smoking, consumption of alcohol, dietary factors, and occupational exposures, may be responsible for the increased incidence of pancreatic cancer. Survival for pancreatic cancer remains low, and prevention by behavioural modification and controlling risk factors could save thousands of lives each year. Updated statistics on the epidemiology of pancreatic cancer along with studies allowing a better understanding of the risk factors are needed in the near future and are essential for the primary prevention of this disease.

Conflict of interest

The authors declare no conflict of interest.

References

1. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Pińeros M, Znaor A, Soerjomataram I, Bray F. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. 2018. Available from: https://gco.iarc.fr/today. Accessed 16 Feb 2019.
2. Rawla P, Sunkara T, Muralidharan P, Raj JP. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn) 2018; 22: 141-150.
3. Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, Gavin A, Visser O, Bray F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-387.
4. Malvezzi M, Carioli G, Bertuccio P, Boffetta P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2019 with focus on breast cancer. Ann Oncol 2019; 30: 781-787.
5. Besselink M. The Value of International Collaboration in Pancreatic Cancer Research: EURECCA. Ann Surg Oncol 2019; 26: 705-706.
6. Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol 2019; 10: 10-27.
7. Nieß H, Kleespies A, Andrassy J et al. Pankreaskarzinom im hohen Alter. Der Chirurg 2013; 84: 291-295.
8. Lee HL, Peng CM, Huang CY, Wu SY, Tsai MC, Wang CC, Chen SL, Lin CC, Huang CN, Sung WW. Is mortality- to incidence ratio associated with health disparity in pancreatic cancer? A cross-sectional database analysis of 57 countries. BMJ Open 2018; 8: e020618.
9. Ferlay J, Partensky C, Bray F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. Acta Oncologica 2016; 55: 1158-1160.
10. Minicozzi P, Cassetti T, Vener C, Sant M. Analysis of incidence, mortality and survival for pancreatic and biliary tract cancers across Europe, with assessment of influence of revised European age standardisation on estimates. Cancer Epidemiol 2018; 55: 52-60.
11. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Gastroenterology Rev 2019; 14: doi:10.5114/pg.2018.81072.
12. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Gastroenterology Rev 2019; 14: 26-38
13. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2014; 136: E359-E386.
14. Wu W, He XK, Yang L, Wang Q, Bian X, Ye J, Li Y, Li L. Rising trends in pancreatic cancer incidence and mortality in 2000-2014. Clin Epidemiol 2018; 10: 789-797.
15. Wood HE, Gupta S, Kang JY, Quinn MJ, Maxwell JD, Mudan S, Majeed A. Pancreatic cancer in England and Wales 1975-2000: patterns and trends in incidence, survival and mortality. Aliment Pharmacol Ther 2006; 23: 1205-1214.
16. Levi F, Lucchini F, Negri E, La Vecchia C. Pancreatic cancer mortality in Europe: the leveling of an epidemic. Pancreas 2003; 27: 139-142.
17. Yeo TP, Hruban RH, Leach SD, Pluth T, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, Iacobuzio-Donahue CA, Maitra A, Goggins M, Canto MI, Abrams RA, Laheru D, Jaffee EM, Hidalgo M, Yeo CJ. Pancreatic cancer. Curr Probl Cancer 2002; 26: 176-275.
18. De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E, Bielska-Lasota M, Engholm G, Nennecke A, Siesling S, Berrino F, Capocaccia R; EUROCARE-5 Working Group. Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5 – a population-based study. Lancet Oncol 2014; 15: 23-34.
19. Pancreatic cancer survival statistics. Cancer Research UK [Internet]. Available from: https://www.cancerresearchuk.org/ health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer/survival#ref-4. Accessed 18 Feb 2019. .
20. Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Tomorrow. Lyon, France: International Agency for Research on Cancer. 2018. Available from: https://gco.iarc.fr/tomorrow. Accessed 16 Feb 2019.
21. Cancer survival in England Statistical bulletins – Office for National Statistics [Internet]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/cancersurvivalinenglandadultsdiagnosed/previousReleases. Accessed 18 Feb 2019.
22. Carrato A, Falcone A, Ducreux M, Valle JW, Parnaby A, Djazouli K, Alnwick-Allu K, Hutchings A, Palaska C, Parthenaki I. A systematic review of the burden of pancreatic cancer in Europe: real-world impact on survival, quality of life and costs. J Gastrointest Cancer 2015; 46: 201-211.
23. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 122. https://monographs.iarc.fr/agents-classified-by-the-iarc/. Accessed 20 Feb 2019.
24. Lowenfels AB, Maisonneuve P. Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol 2006; 20: 197-209.
25. Brown KF, Rumgay H, Dunlop C, Ryan M, Quartly F, Cox A, Deas A, Elliss-Brookes L, Gavin A, Hounsome L, Huws D, Ormiston-Smith N, Shelton J, White C, Parkin DM. The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015. Br J Cancer 2018; 118: 1130-1141.
26. Bosetti C, Lucenteforte E, Silverman DT, Petersen G, Bracci PM, Ji BT, Negri E, Li D, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Bertuccio P, Gao YT, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Boffetta P, La Vecchia C. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 2012; 23: 1880-1888.
27. Zou L, Zhong R, Shen N, Chen W, Zhu B, Ke J, Lu X, Zhang T, Lou J, Wang Z, Liu L, Qi L, Miao X. Non-linear dose-response relationship between cigarette smoking and pancreatic cancer risk: evidence from a meta-analysis of 42 observational studies. Eur J Cancer 2014; 50: 193-203.
28. Vrieling A, Bueno-de-Mesquita HB, Boshuizen HC, Michaud DS, Severinsen MT, Overvad K, Olsen A, Tjønne-land A, Clavel-Chapelon F, Boutron-Ruault MC, Kaaks R, Rohrmann S, Boeing H, Nöthlings U, Trichopoulou A, Moutsiou E, Dilis V, Palli D, Krogh V, Panico S, Tumino R, Vineis P, van Gils CH, Peeters PH, Lund E, Gram IT, Rodríguez L, Agudo A, Larrańaga N, Sánchez MJ, Navarro C, Barricarte A, Manjer J, Lindkvist B, Sund M, Ye W, Bingham S, Khaw KT, Roddam A, Key T, Boffetta P, Duell EJ, Jenab M, Gallo V, Riboli E. Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2010; 126: 2394-2403.
29. Bertuccio P, La Vecchia C, Silverman DT, Petersen GM, Bracci PM, Negri E, Li D, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham ET, Bamlet WR, Holly EA, Lucenteforte E, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Bosetti C, Boffetta P. Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2011; 22: 1420-1426.
30. Burkey MD, Feirman S, Wang H, Choudhury SR, Grover S, Johnston FM. The association between smokeless tobacco use and pancreatic adenocarcinoma: a systematic review. Cancer Epidemiol 2014; 38: 647-653.
31. Araghi M, Rosaria Galanti M, Lundberg M, Lager A, Engström G, Alfredsson L, Knutsson A, Norberg M, Sund M, Wennberg P, Trolle Lagerros Y, Bellocco R, Pedersen NL, Östergren PO, Magnusson C. Use of moist oral snuff (snus) and pancreatic cancer: Pooled analysis of nine prospective observational studies. Int J Cancer 2017; 141: 687-693.
32. Carreras-Torres R, Johansson M, Gaborieau V, Haycock PC, Wade KH, Relton CL, Martin RM, Davey Smith G, Brennan P. The role of obesity, type 2 diabetes, and metabolic factors in pancreatic cancer: a mendelian randomization study. J Natl Cancer Inst 2017; 109. doi: 10.1093/jnci/djx012.
33. Aune D, Greenwood DC, Chan DS, Vieira R, Vieira AR, Navarro Rosenblatt DA, Cade JE, Burley VJ, Norat T. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol 2012; 23: 843-852.
34. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K; International Agency for Research on Cancer Handbook Working Group. Body fatness and cancer – viewpoint of the IARC Working Group. N Engl J Med 2016; 375: 794-798.
35. Luo J, Margolis KL, Adami HO, LaCroix A, Ye W; Women’s Health Initiative Investigators. Obesity and risk of pancreatic cancer among postmenopausal women: the Women’s Health Initiative (United States). Br J Cancer 2008; 99: 527-531.
36. O’Rorke MA, Cantwell MM, Cardwell CR, Mulholland HG, Murray LJ. Can physical activity modulate pancreatic cancer risk? A systematic review and meta-analysis. Int J Cancer 2010; 126: 2957-2968.
37. Rawla P, Thandra KC, Sunkara T. Pancreatic cancer and obesity: epidemiology, mechanism, and preventive strategies. Clin J Gastroenterol 2019. doi: 10.1007/s12328-019-00953-3.
38. Brenner DR, Wozniak MB, Feyt C, Holcatova I, Janout V, Foretova L, Fabianova E, Shonova O, Martinek A, Ryska M, Adamcakova Z, Flaska E, Moskal A, Brennan P, Scelo G. Physical activity and risk of pancreatic cancer in a central European multicenter case-control study. Cancer Causes Control 2014; 25: 669-681.
39. Farris MS, Mosli MH, McFadden AA, Friedenreich CM, Brenner DR. The association between leisure time physical activity and pancreatic cancer risk in adults: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2015; 24: 1462-1473.
40. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 2001; 286: 921-929.
41. Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML, Abbruzzese JL. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 2009; 301: 2553-2562.
42. Yuan C, Bao Y, Wu C, Kraft P, Ogino S, Ng K, Qian ZR, Rubinson DA, Stampfer MJ, Giovannucci EL, Wolpin BM. Prediagnostic body mass index and pancreatic cancer survival. J Clin Oncol 2013; 31: 4229-4234.
43. Wang YT, Gou YW, Jin WW, Xiao M, Fang HY. Association between alcohol intake and the risk of pancreatic cancer: a dose-response meta-analysis of cohort studies. BMC Cancer 2016; 16: 212.
44. Lucenteforte E, La Vecchia C, Silverman D, Petersen GM, Bracci PM, Ji BT, Bosetti C, Li D, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Gao YT, Negri E, Hassan M, Cotterchio M, Su J, Maisonneuve P, Boffetta P, Duell EJ. Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2012; 23: 374-382.
45. Tramacere I, Scotti L, Jenab M, Bagnardi V, Bellocco R, Rota M, Corrao G, Bravi F, Boffetta P, La Vecchia C. Alcohol drinking and pancreatic cancer risk: a meta-analysis of the dose-risk relation. Int J Cancer 2010; 126: 1474-1486.
46. Rahman F, Cotterchio M, Cleary SP, Gallinger S. Association between alcohol consumption and pancreatic cancer risk: a case-control study. PLoS One 2015; 10: e0124489.
47. Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, Scotti L, Jenab M, Turati F, Pasquali E, Pelucchi C, Galeone C, Bellocco R, Negri E, Corrao G, Boffetta P, La Vecchia C. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer 2015; 112: 580-593.
48. Larsson SC, Wolk A. Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies. Br J Cancer 2012; 106: 603-607.
49. Thiebaut AC, Jiao L, Silverman DT, Cross AJ, Thompson FE, Subar AF, Hollenbeck AR, Schatzkin A, Stolzenberg-Solomon RZ. Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study. J Natl Cancer Inst 2009; 101: 1001-1011.
50. Nöthlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, Kolonel LN. Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst 2005; 97: 1458-1465.
51. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. Am J Epidemiol 2003; 157: 1115-1125.
52. Michaud DS, Skinner HG, Wu K, Hu F, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary patterns and pancreatic cancer risk in men and women. J Natl Cancer Inst 2005; 97: 518-524.
53. Rohrmann S, Linseisen J, Nothlings U, Overvad K, Egeberg R, Tjønneland A, Boutron-Ruault MC, ClavelChapelon F, Cottet V, Pala V, Tumino R, Palli D, Panico S, Vineis P, Boeing H, Pischon T, Grote V, Teucher B, Khaw KT, Wareham NJ, Crowe FL, Goufa I, Orfanos P, Trichopoulou A, Jeurnink SM, Siersema PD, Peeters PH, Brustad M, Engeset D, Skeie G, Duell EJ, Amiano P, Barricarte A, Molina-Montes E, Rodríguez L, Tormo MJ, Sund M, Ye W, Lindkvist B, Johansen D, Ferrari P, Jenab M, Slimani N, Ward H, Riboli E, Norat T, Bueno-de-Mesquita HB. Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2013; 132: 617-624.
54. Paluszkiewicz P, Smolinska K, Debinska I, Turski WA. Main dietary compounds and pancreatic cancer risk. The quantitative analysis of case-control and cohort studies. Cancer Epidemiol 2012; 36: 60-67.
55. Wu L, Wang Z, Zhu J, Murad AL, Prokop LJ, Murad MH. Nut consumption and risk of cancer and type 2 diabetes: a systematic review and meta-analysis. Nutr Rev 2015; 73: 409-425.
56. Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Am J Clin Nutr 2016; 103: 218-230.
57. Buha A, Wallace D, Matovic V, Schweitzer A, Oluic B, Micic D, Djordjevic V. Cadmium exposure as a putative risk factor for the development of pancreatic cancer: three different lines of evidence. BioMed Res Int 2017; 2017: 1981837.
58. Yorifuji T, Tsuda T, Grandjean P. Unusual cancer excess after neonatal arsenic exposure from contaminated milk powder. J Natl Cancer Inst 2010; 102: 360-361.
59. Bosch de Basea M, Porta M, Alguacil J, Puigdomènech E, Gasull M, Garrido JA, López T; PANKRAS II Study Group. Relationships between occupational history and serum concentrations of organochlorine compounds in exocrine pancreatic cancer. Occup Environ Med 2011; 68: 332-338.
60. Bardia A, Tleyjeh IM, Cerhan JR, Sood AK, Limburg PJ, Erwin PJ, Montori VM. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc 2008; 83: 23-34.
61. Etminan M, FitzGerald JM, Gleave M, Chambers K. Intake of selenium in the prevention of prostate cancer: a systematic review and meta-analysis. Cancer Causes Control 2005; 16: 1125-1131.
62. Santibanez M, Vioque J, Alguacil J, de la Hera MG, Moreno-Osset E, Carrato A, Porta M, Kauppinen T. Occupational exposures and risk of pancreatic cancer. Eur J Epidemiol 2010; 25: 721-730.
63. Olson SH, Kurtz RC. Epidemiology of pancreatic cancer and the role of family history. J Surg Oncol 2013; 107: 1-7.
64. Shindo K, Yu J, Suenaga M, Fesharakizadeh S, Cho C, Macgregor-Das A, Siddiqui A, Witmer PD, Tamura K, Song TJ, Navarro Almario JA, Brant A, Borges M, Ford M, Barkley T, He J, Weiss MJ, Wolfgang CL, Roberts NJ, Hruban RH, Klein AP, Goggins M. Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol 2017; 35: 3382-3390.
65. Klein AP. Genetic susceptibility to pancreatic cancer. Mol Carcinog 2012; 51: 14-24.
66. Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, Lilyquist J, Na J, Moore R, Antwi SO, Bamlet WR, Chaffee KG, DiCarlo J, Wu Z, Samara R, Kasi PM, McWilliams RR, Petersen GM, Couch FJ. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA 2018; 319: 2401-2409.
67. Wolpin BM, Kraft P, Gross M, Helzlsouer K, Bueno-de-Mesquita HB, Steplowski E, Stolzenberg-Solomon RZ, Arslan AA, Jacobs EJ, Lacroix A, Petersen G, Zheng W, Albanes D, Allen NE, Amundadottir L, Anderson G, BoutronRuault MC, Buring JE, Canzian F, Chanock SJ, Clipp S, Gaziano JM, Giovannucci EL, Hallmans G, Hankinson SE, Hoover RN, Hunter DJ, Hutchinson A, Jacobs K, Kooperberg C, Lynch SM, Mendelsohn JB, Michaud DS, Overvad K, Patel AV, Rajkovic A, Sanchéz MJ, Shu XO, Slimani N, Thomas G, Tobias GS, Trichopoulos D, Vineis P, Virtamo J, Wactawski-Wende J, Yu K, Zeleniuch-Jacquotte A, Hartge P, Fuchs CS. Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium. Cancer Res 2010; 70: 1015-1023.
68. Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, Bueno-de-Mesquita HB, Gross M, Helzlsouer K, Jacobs EJ, LaCroix A, Zheng W, Albanes D, Bamlet W, Berg CD, Berrino F, Bingham S, Buring JE, Bracci PM, Canzian F, Clavel-Chapelon F, Clipp S, Cotterchio M, de Andrade M, Duell EJ, Fox JW Jr, Gallinger S, Gaziano JM, Giovannucci EL, Goggins M, González CA, Hallmans G, Hankinson SE, Hassan M, Holly EA, Hunter DJ, Hutchinson A, Jackson R, Jacobs KB, Jenab M, Kaaks R, Klein AP, Kooperberg C, Kurtz RC, Li D, Lynch SM, Mandelson M, McWilliams RR, Mendelsohn JB, Michaud DS, Olson SH, Overvad K, Patel AV, Peeters PH, Rajkovic A, Riboli E, Risch HA, Shu XO, Thomas G, Tobias GS, Trichopoulos D, Van Den Eeden SK, Virtamo J, WactawskiWende J, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Chanock SJ, Hartge P, Hoover RN. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 2009; 41: 986-990.
69. Yamada A, Komaki Y, Komaki F, Micic D, Zullow S, Sakuraba A. Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis. Lancet Oncol 2018; 19: 758-767.
70. Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, Dimagno EP, Andrén-Sandberg A, Domellöf L. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 1993; 328: 1433-1437.
71. Stevens RJ, Roddam AW, Beral V. Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer 2007; 96: 507-509.
72. Aggarwal G, Kamada P, Chari ST. Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers. Pancreas 2013; 42: 198-201.
73. Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, Bracci PM, Neale RE, Muscat J, Anderson K, Gallinger S, Olson SH, Miller AB, Bas Bueno-de-Mesquita H, Scelo G, Janout V, Holcatova I, Lagiou P, Serraino D, Lucenteforte E, Fabianova E, Ghadirian P, Baghurst PA, Zatonski W, Foretova L, Fontham E, Bamlet WR, Holly EA, Negri E, Hassan M, Prizment A, Cotterchio M, Cleary S, Kurtz RC, Maisonneuve P, Trichopoulos D, Polesel J, Duell EJ, Boffetta P, La Vecchia C. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol 2014; 25: 2065-2072.
74. Rawla P, Vellipuram AR, Bandaru SS, Pradeep Raj J. Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. Endocrinol Diabetes Metab Case Rep 2017; 2017: doi: 10.1530/EDM-17-0081.
75. Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology 2008; 134: 981-987.
76. Chari ST, Leibson CL, Rabe KG, Timmons LJ, Ransom J, de Andrade M, Petersen GM. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 2008; 134: 95-101.
77. Duell EJ, Lucenteforte E, Olson SH, Bracci PM, Li D, Risch HA, Silverman DT, Ji BT, Gallinger S, Holly EA, Fontham EH, Maisonneuve P, Bueno-de-Mesquita HB, Ghadirian P, Kurtz RC, Ludwig E, Yu H, Lowenfels AB, Seminara D, Petersen GM, La Vecchia C, Boffetta P. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2012; 23: 2964-2970.
78. Raimondi S, Lowenfels AB, Morselli-Labate AM, Maisonneuve P, Pezzilli R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol 2010; 24: 349-358.
79. Ekbom A, McLaughlin JK, Karlsson BM, Nyrén O, Gridley G, Adami HO, Fraumeni JF Jr. Pancreatitis and pancreatic cancer: a population-based study. J Natl Cancer Inst 1994; 86: 625-627.
80. Rawla P, Sunkara T, Thandra KC, Gaduputi V. Hypertriglyceridemia-induced pancreatitis: updated review of current treatment and preventive strategies. Clin J Gastroenterol 2018; 11: 441-448.
81. Turati F, Galeone C, Edefonti V, Ferraroni M, Lagiou P, La Vecchia C, Tavani A. A meta-analysis of coffee consumption and pancreatic cancer. Ann Oncol 2012; 23: 311-318.
82. Risch HA, Lu L, Kidd MS, Wang J, Zhang W, Ni Q, Gao YT, Yu H. Helicobacter pylori seropositivities and risk of pancreatic carcinoma. Cancer Epidemiol Biomarkers Prev 2014; 23: 172-178.
83. Huang J, Magnusson M, Torner A, Ye W, Duberg AS. Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: a nationwide study in Sweden. Br J Cancer 2013; 109: 2917-2923.
84. Mahale P, Torres HA, Kramer JR, Hwang LY, Li R, Brown EL, Engels EA. Hepatitis C virus infection and the risk of cancer among elderly US adults: a registry-based case-control study. Cancer 2017; 123: 1202-1211.
85. Rawla P, Bandaru SS, Vellipuram AR. Review of infectious etiology of acute pancreatitis. Gastroenterology Res 2017; 10: 153-158.

Address for correspondence:

Graeme Hawksworth
Department of Medicine
School of Medicine
Cardiff University
Cardiff, CF10 3AT, UK
E-mail: grawksworth@outlook.com
Copyright: © 2019 Jan Kochanowski University in Kielce This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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