Paolo Boffetta, Elisabete Weiderpass, Timo Partanen, Timo Kauppinen
Pancreatic cancer (ICD-9 157; ICD-10 C25), a highly fatal malignancy, ranks amongst the 15 most common cancers globally but belongs to the ten most common cancers in the populations of developed countries, accounting for 2 to 3% of all new cases of cancer (IARC 1993). An estimated 185,000 new cases of pancreatic cancer occurred globally in 1985 (Parkin, Pisani and Ferlay 1993). The incidence rates of pancreatic cancer have been increasing in developed countries. In Europe, the increase has levelled off, except in the UK and some Nordic countries (Fernandez et al. 1994). The incidence and mortality rates rise steeply with advancing age between 30 and 70 years. The age-adjusted male/female ratio of new cases of pancreatic cancer is 1.6/1 in developed countries but only 1.1/1 in developing countries.
High annual incidence rates of pancreatic cancer (up to 30/100,000 for men; 20/100,000 for women) in the period 1960-85, have been recorded for New Zealand Maoris, Hawaiians, and in Black populations in the US. Regionally, the highest age-adjusted rates in 1985 (over 7/100,000 for men and 4/100,000 in women) were reported for both genders in Japan, North America, Australia, New Zealand, and Northern, Western and Eastern Europe. The lowest rates (up to 2/100,000 for both men and women) were reported in the regions of West and Middle Africa, South-eastern Asia, Melanesia, and in temperate South America (IARC 1992; Parkin, Pisani and Ferlay 1993).
Comparisons between populations in time and space are subject to several cautions and interpretation difficulties because of variations in diagnostic conventions and technologies (Mack 1982).
The vast majority of pancreatic cancers occur in the exocrine pancreas. The major symptoms are abdominal and back pain and weight loss. Further symptoms include anorexia, diabetes and obstructive jaundice. Symptomatic patients are subjected to procedures such as a series of blood and urine tests, ultrasound, computerized tomography, cytological examination and pancreatoscopy. Most patients have metastases at diagnosis, which makes their prognosis bleak.
Only 15% of patients with pancreatic cancer are operable. Local recurrence and distant metastases occur frequently after surgery. Irradiation therapy or chemotherapy do not bring about significant improvements in survival except when combined with surgery on localized carcinomas. Palliative procedures provide little benefit. Despite some diagnostic improvements, survival remains poor. During the period 1983-85, the five-year average survival in 11 European populations was 3% for men and 4% for women (IARC 1995). Very early detection and diagnosis or identification of high-risk individuals may improve the success of surgery. The efficacy of screening for pancreatic cancer has not been determined.
Mortality and incidence of pancreatic cancer do not reveal a consistent global pattern across socio-economic categories.
The dismal picture offered by diagnostic problems and treatment inefficacy is completed by the fact that the causes of pancreatic cancer are largely unknown, which effectively hampers the prevention of this fatal disease. The unique established cause of pancreatic cancer is tobacco smoking, which explains about 20-50% of the cases, depending on the smoking patterns of the population. It has been estimated that elimination of tobacco smoking would decrease the incidence of pancreatic cancer by about 30% worldwide (IARC 1990). Alcohol consumption and coffee drinking have been suspected as increasing the risk of pancreatic cancer. On closer scrutiny of the epidemiological data, however, coffee consumption appears unlikely to be causally connected to pancreatic cancer. For alcoholic beverages, the only causal link with pancreatic cancer is probably pancreatitis, a condition associated with heavy alcohol consumption. Pancreatitis is a rare but potent risk factor of pancreatic cancer. It is possible that some as yet unidentified dietary factors might account for a part of the aetiology of pancreatic cancer.
Workplace exposures may be causally associated with pancreatic cancer. Results of several epidemiological studies that have linked industries and jobs with an excess of pancreatic cancer are heterogeneous and inconsistent, and exposures shared by alleged high-risk jobs are hard to identify. The population aetiologic fraction for pancreatic cancer from occupational exposures in Montreal, Canada, has been estimated to lie between 0% (based on recognized carcinogens) and 26% (based on a multi-site case-control study in the Montreal area, Canada) (Siemiatycki et al. 1991).
No single occupational exposure has been confirmed to increase the risk of pancreatic cancer. Most of the occupational chemical agents that have been associated with an excess risk in epidemiological studies emerged in one study only, suggesting that many of the associations may be artefacts from confounding or chance. If no additional information, e.g., from animal bio-assays, is available, the distinction between spurious and causal associations presents formidable difficulties, given the general uncertainty about the causative agents involved in the development of pancreatic cancer. Agents associated with increased risk include aluminium, aromatic amines, asbestos, ashes and soot, brass dust, chromates, combustion products of coal, natural gas and wood, copper fumes, cotton dust, cleaning agents, grain dust, hydrogen fluoride, inorganic insulation dust, ionizing radiation, lead fumes, nickel compounds, nitrogen oxides, organic solvents and paint thinners, paints, pesticides, phenol-formaldehyde, plastic dust, polycyclic aromatic hydrocarbons, rayon fibres, stainless steel dust, sulphuric acid, synthetic adhesives, tin compounds and fumes, waxes and polishes, and zinc fumes (Kauppinen et al. 1995). Among these agents, only aluminium, ionizing radiation and unspecified pesticides have been associated with excess risk in more than one study.