Risk Of Exocrine Pancreatic Cancer Research Articles

Toenail concentrations of trace elements and occupational history in pancreatic cancer

BackgroundSome occupations potentially entailing exposure to cadmium, arsenic, lead, selenium, nickel, and chromium have been associated with an increased risk of exocrine pancreatic cancer (EPC), but no studies have assessed whether body concentrations of such compounds differed among subjects occupationally exposed and unexposed. No studies which found that exposure to such metals increased the risk of EPC assessed whether past occupations were the source of exposure. ObjectiveThe aim was to analyse the relationship between toenail concentrations of trace elements and occupational history in EPC patients. MethodsThe study included 114 EPC cases personally interviewed on occupational history and lifestyle factors. Occupations were coded according to the International Standard Classification of Occupations 1988. Selected occupational exposures were assessed by two industrial hygienists and with the Finnish job-exposure matrix (Finjem). Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Adjusted geometric means (aGMs) and 95% confidence intervals (95% CI) were calculated. ResultsPatients occupationally exposed to aromatic hydrocarbon solvents (AHs) had higher concentrations of cadmium, manganese, lead, iron and vanadium. The aGM of cadmium concentrations for cases exposed to any pesticide was 0.056 μg/g [95% CI: 0.029–0.108], and, for unexposed cases, 0.023 μg/g [0.017–0.031]. Patients occupationally exposed to pesticides had higher concentrations of cadmium and manganese. Higher concentrations of vanadium, lead and arsenic were related to exposure to formaldehyde. Vanadium and lead were also associated with exposure to chlorinated hydrocarbon solvents, and arsenic was related to exposure to polycyclic aromatic hydrocarbons (PAHs). ConclusionsPatients occupationally exposed to AHs, pesticides, chlorinated hydrocarbon solvents, formaldehyde, volatile sulphur compounds and PAHs had higher concentrations of several metals. These elements may account for some of the occupational risks previously reported for pancreatic cancer.

Association between ABO blood types and sporadic pancreatic neuroendocrine tumors in the Chinese Han population.

BackgroundAlthough the relationship between non-O blood types and the risk of exocrine pancreatic cancer has been demonstrated, the association between ABO blood types and sporadic pancreatic neuroendocrine tumor (PNET) has not been reported thus far.MethodsThis hospital-based, case-control study included 387 patients with PNET and 542 age- and sex-matched controls. Unconditional multivariable logistic regression analysis was performed to estimate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs). The relationship between ABO blood types and clinicopathologic features was also analyzed.ResultsAfter adjusting for age, sex, smoking status, alcohol drinking, and first-degree family history of any cancer, the AORs (95% CI) of functional PNET were 0.87 (0.59–1.28) for blood type A, 0.86 (0.58–1.28) for blood type B, and 0.71 (0.39–1.26) for blood type AB compared with subjects with blood type O. A similar ABO blood-type distribution was observed among cases with non-functional PNETs compared with controls. On comparing blood type B with non-B blood type, cases with non-functional PNETs had marginally higher rates of lymph node invasion (P = 0.047), distant metastasis (P = 0.044), and advanced European Neuroendocrine Tumor Society Stage (P = 0.040).ConclusionsThere is no association between the ABO blood group and the development of functional and non-functional PNETs. The ABO blood types are not associated with the clinicopathologic features in patients with functional and non-functional PNETs.

Pancreatic cancer risk and levels of trace elements

Background and AimsKnowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a...

Relationships between occupational history and serum concentrations of organochlorine compounds in exocrine pancreatic cancer

BackgroundPrevious studies investigating associations between occupational history and risk of exocrine pancreatic cancer (EPC) did not use biomarkers of exposure. The only two studies that measured internal concentrations of organochlorine...

Statins and pancreatic cancer risk: a nested case–control study

To investigate the relationship between statin use and pancreatic cancer risk. A nested case-control study was conducted within the UK GPRD. Cases had a diagnosis of primary malignant neoplasia of the exocrine pancreas. Controls were matched with cases on general practice site, sex and year of birth. Exposure of interest was exposure to statins since entry into the GPRD until 1 year before the case diagnosis date. Conditional logistic regression analyses were used to generate ORs and 95% CI associated with statin use compared to non-use. A total of 1,141 pancreatic cancer cases and 7,954 controls were identified. Any use of a statin since entry into the GPRD (excluding the year prior to diagnosis) was not associated with the risk of pancreatic cancer OR 0.93 (95% CI, 0.76-1.14). Neither dose nor duration of statin use affected pancreatic cancer risk. When dose and duration of statin use combined were assessed, no evidence of reduced risk was seen for long-term users of high-dose statins OR 0.71 (0.42-1.20). Statin type (simvastatin vs atorvastatin) was not associated with pancreatic cancer risk. Statin use at doses for managing hypercholesterolaemia, in a UK population, was not associated with the risk of exocrine pancreatic cancer.

Occupational exposures and risk of pancreatic cancer

The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

Insulin, Glucose, Insulin Resistance, and Pancreatic Cancer in Male Smokers

Obesity, diabetes mellitus, and glucose intolerance have been associated with increased pancreatic cancer risk; however, prediagnostic serum insulin concentration has not been evaluated as a predictor of this malignancy. To investigate whether prediagnostic fasting glucose and insulin concentrations and insulin resistance are associated with subsequent incidence of exocrine pancreatic cancer in a cohort of male smokers. A case-cohort prospective study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-1988) cohort of 29,133 male Finnish smokers ages 50 to 69 years. The study included 400 randomly sampled subcohort control participants and 169 incident pancreatic cancer cases that occurred after the fifth year of follow-up. All participants were followed up through December 2001 (up to 16.7 years of follow-up). Incident exocrine pancreatic cancer identified from the Finnish Cancer Registry. After adjusting for age, smoking, and body mass index, higher baseline fasting serum concentrations of glucose, insulin, and insulin resistance were positively associated with pancreatic cancer. The presence of biochemically defined diabetes mellitus (glucose, > or =126 mg/dL [> or =6.99 mmol/L]) and insulin concentration in the highest vs lowest quartile both showed a significant 2-fold increased risk (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.04-4.35; and HR, 2.01; 95% CI, 1.03-3.93; respectively). There were significant interactions for all the biomarker exposures by follow-up time, such that the positive associations were stronger among the cases that occurred more than 10 years after baseline (highest vs lowest quartile: glucose, HR, 2.16; 95% CI, 1.05-4.42; P for trend = .02; insulin, HR, 2.90; 95% CI, 1.22-6.92; P for trend = .005; and insulin resistance, HR, 2.71; 95% CI, 1.19-6.18; P for trend = .006). These results support the hypothesis that exposure to higher insulin concentrations and insulin resistance predicts the risk of exocrine pancreatic cancer.

Meat and Fat Intake as Risk Factors for Pancreatic Cancer: The Multiethnic Cohort Study

Meat intake has been associated with risk of exocrine pancreatic cancer, but previous findings have been inconsistent. This association has been attributed to both the fat and cholesterol content of meats and to food preparation methods. We analyzed data from the prospective Multiethnic Cohort Study to investigate associations between intake of meat, other animal products, fat, and cholesterol and pancreatic cancer risk. During 7 years of follow-up, 482 incident pancreatic cancers occurred in 190,545 cohort members. Dietary intake was assessed using a quantitative food frequency questionnaire. Associations for foods and nutrients relative to total energy intake were determined by Cox proportional hazards models stratified by gender and time on study and adjusted for age, smoking status, history of diabetes mellitus and familial pancreatic cancer, ethnicity, and energy intake. Statistical tests were two-sided. The strongest association was with processed meat; those in the fifth quintile of daily intake (g/1000 kcal) had a 68% increased risk compared with those in the lowest quintile (relative risk = 1.68, 95% confidence interval = 1.35 to 2.07; Ptrend < .01). The age-adjusted yearly incidence rates per 100,000 persons for the respective quintiles were 41.3 and 20.2. Intakes of pork and of total red meat were both associated with 50% increases in risk, comparing the highest with the lowest quintiles (both Ptrend < .01). There were no associations of pancreatic cancer risk with intake of poultry, fish, dairy products, eggs, total fat, saturated fat, or cholesterol. Intake of total and saturated fat from meat was associated with statistically significant increases in pancreatic cancer risk but that from dairy products was not. Red and processed meat intakes were associated with an increased risk of pancreatic cancer. Fat and saturated fat are not likely to contribute to the underlying carcinogenic mechanism because the findings for fat from meat and dairy products differed. Carcinogenic substances related to meat preparation methods might be responsible for the positive association.

A prospective study of folate intake and the risk of pancreatic cancer in men and women.

Laboratory and human studies suggest that folate intake may influence the risk of some cancers. However, prospective information about the relation between folate intake and the risk of exocrine pancreatic cancer is limited. The authors examined the relation of dietary folate intake to the risk of pancreatic cancer in two large prospective US cohorts. Folate intake was assessed by food frequency questionnaire in 1984 in women and in 1986 in men. Multivariate relative risks were adjusted for age, energy intake, cigarette smoking, body mass index, diabetes, and height. During 14 years' follow-up in each cohort, 326 incident cases of pancreatic cancer were identified. Compared with participants in the lowest category of folate intake, participants in increasing 100- micro g categories of total energy-adjusted folate intake had pooled multivariate relative risks for pancreatic cancer of 1.08, 1.10, and 1.03 (95% confidence interval: 0.74, 1.43; p(trend) = 0.99). For energy-adjusted folate from food, the pooled relative risks for increasing 100- micro g categories of intake were 0.81, 0.89, and 0.66 (95% confidence interval: 0.42, 1.03; p(trend) = 0.12). There was no statistical interaction between folate intake and methionine, alcohol, fat, or caffeine. The results from these two large prospective cohorts do not support a strong association between energy-adjusted folate intake and the risk of pancreatic cancer.

Occupational exposure to organic solvents and K-ras mutations in exocrine pancreatic cancer

Occupational exposure to hydrocarbon solvents has been found to be associated with an increased risk of exocrine pancreatic cancer (EPC), the human tumor with the highest prevalence of K-ras mutations. Ras genes are critical DNA targets for chemical carcinogens. We analysed the relationship between past occupational exposure to hydrocarbon solvents and mutations in codon 12 of the K-ras gene in 107 incident cases of EPC. Information on occupational factors and life-style was obtained from personal interviews conducted during hospital stay. Occupational exposure to hydrocarbon solvents (aliphatic, aromatic, chlorinated, benzene, other organic solvents) was examined using two methods: expert assessment and the Finnish job-exposure matrix (Finjem). Exposure among K-ras mutated EPC cases (n = 83) was compared with that of K-ras wild-type EPC cases (n = 24). An association between K-ras mutations and solvent exposure was observed with Finjem but barely so with the expert assessment. Over 7-fold increased odds ratios (OR) were found for every group of solvents evaluated with Finjem (all P < 0.05). On the basis of the expert assessment, K-ras mutations were significantly associated only with exposure to benzene in men (OR = 7.07, P < 0.05). When requiring exposure to have occurred according to both the experts and Finjem, over 4-fold risks were obtained for aromatic, aliphatic, and for "any hydrocarbon solvent". A significantly higher proportion of cases with a mutation from glycine to valine (GGT-->GTT) or to aspartic acid (GGT-->GAT) were exposed to a hydrocarbon solvent. The results raise the possibility that hydrocarbon solvents might be involved in the pathogenesis of EPC, possibly through indirect modulation of K-ras activation. Since this is only the first study on occupational exposures and K-ras mutations in EPC, studies able to refute or to confirm the findings are required before public health implications, if any, are assessed.

Gene-Environment Interactions in Pancreatic Cancer

Exocrine pancreatic cancer remains a major cause of cancer death in Western populations. Despite many efforts, little is known about its etiology. Tobacco is the only established cause, although the proportion of cases of exocrine pancreatic cancer attributed to it is only 30%. A family history of pancreatic cancer accounts for 10% of the cases of this disease. A large proportion of cases are due to yet unrecognized factors. The combined contribution of genetic susceptibility and environmental factors has rarely been considered. A higher risk of exocrine pancreatic cancer has been observed for patients with hereditary pancreatitis who smoked. It has also been suggested that CFTR mutations and alcohol could interact in the development of exocrine pancreatic cancer. Common variants in a large number of genes could act as low-penetrance alleles. Little is known about their role as susceptibility markers for exocrine pancreatic cancer, except for metabolic enzymes. A few studies have assessed the association between polymorphisms in these genes and exocrine pancreatic cancer. Surprisingly, none of them observed an interaction with tobacco consumption. The reality may be more complex; exocrine pancreatic cancer is genetically heterogeneous and it could involve many somatic and heritable mutations. Gene-gene interactions and endogenous factors, among others, can contribute to tumor development. Future epidemiological studies should consider all of these aspects together.

Occupation and pancreatic cancer in Spain: a case-control study based on job titles. PANKRAS II Study Group.

Occupational exposures may increase the risk of exocrine pancreatic cancer. This study aimed to identify occupations that in Spain may be associated with such risk. Incident cases of pancreatic cancer and hospital controls were prospectively identified and interviewed during their hospital stay. Occupational history was obtained by direct interview with the patient and was available for 164 (89%) of 185 pancreatic cancer cases and for 238 (90%) of 264 controls. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. A significant increased odds ratio (OR) was observed in men for 'physical, chemistry and engineering science technicians'. Elevated risks were also found for 'metal moulders, sheet-metal workers, structural metal workers, welders and related workers', 'painters and varnishers' and 'machinery mechanics and fitters'. 'Agricultural workers' did not present an increased risk for pancreas cancer in men. In women, however, high OR were observed for 'agricultural workers' and for 'textile and garment workers'. Most associations remained unchanged after considering long duration of the exposure and the period 5-15 years before diagnosis. Few occupations were at increased risk for pancreatic cancer, and the associations observed are in accordance with previous studies. The increases in risk observed for women in agricultural and textile jobs, and for men in the manufacture of dyes and pigments may deserve further attention.