Risk assessment for PFOA and kidney cancer based on a pooled analysis of two studies.

INTRODUCTION: Perfluorooctanoic acid (PFOA) has been associated with kidney cancer in human studies. METHODS: We conducted a pooled analysis of two large studies of PFOA and renal cell carcinoma (RCC, the most common type of kidney cancer); one from the National Cancer Institute (NCI) (324 cases and controls), and a second from the C8 Science Panel (103 cases and 511 controls). Serum PFOA levels were estimated a median of 8 years before diagnosis. Analyses were conducted via conditional logistic regression. Lifetime risk of kidney cancer per unit serum PFOA concentration and per unit dose were calculated. RESULTS: The 25th, 50th and 75th percentiles of serum PFOA levels were 4.8, 7.3, and 23.9 ng/ml for the pooled analysis. The preferred model for the pooled datawas a two-piece linear spline model (knot at 12.5 ng/ml serum PFOA); the log odds of RCC increased 0.1349 per 1 ng/ml increase in serum PFOA up to the knot (eg, an OR of 2.02 (1.45-2.80) from the median to the knot), and was flat thereafter. The estimated lifetime excess risk (cancer slope factor) with an exposure of 1 ng/ml was 0.0018, similar to the excess risk of 0.0026 recently reported by CalEPA based on different methods. Assuming a serum half-life of 2.3 years and a distribution volume of 170 ml/kg for PFOA, our results are equivalent to 0.0128 per ng/kg/d of PFOA intake. To limit excess lifetime kidney cancer risk to 1/1,000,000, our data suggest a limit of 0.0015 ng/L (0.0015 ppt) for PFOA in drinking water, similar to CalEPA's proposed Public Health Goal and the new US EPA Drinking Water Health Advisory. CONCLUSIONS: Our results correspond reasonably well with cancer slope factors developed by other investigators using published summary data, and suggest drinking water limits similar to new recommendations by the US EPA.

Investing in prospective cohorts for etiologic study of occupational exposures.

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures.

LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk.

BACKGROUND: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. METHODS: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. RESULTS: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P=0.06) and 1.33 (95% CI 1.05-1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05). CONCLUSIONS: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Dietary intake of meat, fruits, vegetables, and selective micronutrients and risk of bladder cancer in the New England region of the United States.

BACKGROUND: Despite many studies on diet and bladder cancer, there are areas that remain unexplored including meat mutagens, specific vegetable groups, and vitamins from diet. METHODS: We conducted a population-based case-control study of bladder cancer in Maine, New Hampshire, and Vermont. A total of 1171 cases were ascertained through hospital pathology records and cancer registries from 2001 to 2004. Overall, 1418 controls were identified from the Department of Motor Vehicles (<65 years) and Center for Medicaid and Medicare Services (65-79 years) and were frequency-matched to cases by state, sex, and age (within 5 years). Diet was assessed with a self-administered Diet History Questionnaire. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Processed meat intake was positively associated with bladder cancer (highest vs lowest quartile OR: 1.28; 95% CI: 1.00-1.65; P(trend)=0.035), with a stronger association for processed red meat (OR: 1.41; 95% CI: 1.08-1.84; P(trend)=0.024). There were no associations between intake of fruits or vegetables and bladder cancer. We did, however, observe an inverse association with vitamin B12 intake (OR: 0.77; 95% CI: 0.61-0.99; P=0.019). CONCLUSION: Vitamin B12 from diet may be protective against bladder cancer, whereas consuming processed meat may increase risk.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).

BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.

GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis.

Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.

Differential effects of smoking on lung cancer mortality before and after household stove improvement in Xuanwei, China.

BACKGROUND: In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China. METHODS: We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement. RESULTS AND CONCLUSION: We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure.

Work in the textile industry in Spain and bladder cancer.

BACKGROUND/OBJECTIVE: Textile manufacturing is a complex industry that has frequently been associated with bladder cancer. However, results have not been consistent. This study investigated the risk of bladder cancer in Spanish textile workers. METHODS: We analysed data from a multicentre hospital-based case-control study carried out in Spain (1998-2001) including 1219 cases of bladder cancer and 1271 controls. Of those, 126 cases and 122 controls reported a history of employment in the textile industry. Lifetime occupational history was obtained using a computer-assisted personal interview. Occupations, locations and materials used in the textile industry were assessed using a detailed questionnaire and expert assessment. RESULTS: Overall, no increased risk of bladder cancer was found for textile workers, including duration of employment analysis. Increased risks were observed for weavers (OR = 1.82, 95% CI 0.95 to 3.47), for workers in winding/warping/sizing (OR 4.11, 95% CI 1.58 to 10.71) and for those exposed to synthetic materials (OR 1.89, 95% CI 1.00 to 3.56). Working for more than 10 years appeared to be associated with an increased risk for weavers (OR 2.27, 95% CI 0.97 to 5.34), for those who had ever worked in winding/warping/sizing (OR 11.03, 95% CI 1.37, 88.89), for workers in the weaving room (OR 2.94, 95% CI 1.24 to 7.01) and for those exposed to synthetic (OR 2.62, 95% CI 1.14 to 6.01) or cotton (OR 2.00, 95% CI 1.04 to 3.87) materials. Statistically significant higher risks were also found for specific combinations of occupations or locations with exposure to synthetics and cotton. CONCLUSIONS: There was no overall increased risk for textile workers, but increased risks were found for specific groups of workers. Our findings indicate that observed risks in previous studies may be better evaluated by analysis of materials used or section worked within the industry and occupation.

Occupation and bladder cancer in a hospital-based case-control study in Spain.

OBJECTIVES: We investigated the association between occupation and bladder cancer in a hospital-based case-control study conducted in Spain. METHODS: 1219 patients with transitional cell carcinoma of the urinary bladder and 1271 controls selected from 18 hospitals in Spain between June 1998 and September 2000 provided detailed information on life-time occupational history, smoking habits, medical history, and other factors. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for each occupation and industry, adjusting for age, hospital region, smoking duration, and employment in a high-risk occupation for bladder cancer. RESULTS: Statistically significant increased risks were observed among men employed as machine operators in the printing industry (OR 5.4; 95% CI 1.6 to 17.7), among men employed in the transportation equipment industry (OR 1.6; 95% CI 1.1 to 2.6) and among those who had worked for >/=10 years in the electrical/gas/sanitary services (OR 3.9; 95% CI 1.5 to 10.4) and in hotels and other lodgings (OR 3.1; 95% CI 1.3 to 7.3). Men who worked as miscellaneous mechanics and repairers (OR 2.0; 95% CI 1.1 to 3.6) and as supervisors in production occupations (OR 2.1; 95% CI 1.2 to 3.6) also had excess risks for bladder cancer. Male farmers and those who worked in crop and livestock production had decreased risks for bladder cancer. We found no significant associations between occupation or industry and bladder cancer risk among women. CONCLUSIONS: We did not observe excess bladder cancer risk for many of the occupations identified as being a priori at high risk. Examination of more detailed job exposure information should help clarify these associations.

Diet and nutrition as risk factors for multiple myeloma among blacks and whites in the United States.

OBJECTIVES: To explore whether dietary factors contribute to the risk of multiple myeloma and the two-fold higher incidence among blacks compared to whites in the United States. METHODS: Data from a food-frequency questionnaire were analyzed for 346 white and 193 black subjects with multiple myeloma, and 1086 white and 903 black controls who participated in a population-based case-control study of multiple myeloma in three areas of the United States. RESULTS: Elevated risks were associated with obese vs. normal weight (OR = 1.9, 95% confidence interval (CI) = 1.2-3.1 for whites and OR = 1.5, 95% CI = 0.9-2.4 for blacks), while the frequency of obesity was greater for black than white controls. Reduced risks were related to frequent intake of cruciferous vegetables (OR = 0.7, 95% CI = 0.6-0.99) and fish (OR = 0.7, 95% CI = 0.5-0.9) in both races combined, and to vitamin C supplements in whites (OR = 0.6, 95% CI = 0.5-0.9) and blacks (OR = 0.8, 95% CI = 0.5-1.4), with the frequency of vitamin supplement use being greater for white than black controls. However, frequent intake of vitamin C from food and supplements combined was associated with a protective effect in whites (OR = 0.6, 95% CI = 0.4-0.9), but not blacks (OR = 1.2, 95% CI = 0.8-2.1). CONCLUSIONS: The greater use of vitamin C supplements by whites and the higher frequency of obesity among blacks may explain part of the higher incidence of multiple myeloma among blacks compared to whites in the United States. In addition, the increasing prevalence of obesity may have contributed to the upward trend in the incidence of multiple myeloma during recent decades.

Risk factors for pancreatic cancer: a case-control study based on direct interviews.

The etiology of pancreatic cancer is poorly understood, partly because of the inconsistency of findings among case-control studies of pancreatic cancer. Because of the unfavorable prognosis for pancreatic cancer, many case-control studies have been based largely on interviews with next of kin, who are known to report less reliable information on potential risk factors than original respondents. The purpose of this study was to estimate the effects of speculative risk factors such as dietary/nutritional factors and alcohol drinking, as well as those of established risk factors such as cigarette smoking, diabetes mellitus, and family history of pancreatic cancer, on pancreatic cancer risk based solely on direct interviews. This investigation was a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and ten New Jersey counties from August 1986 through April 1989. Direct interviews were conducted with 526 incident cases and 2,153 population controls. This study revealed a significant interaction between body mass index and caloric intake that was consistent by both race and gender. Subjects with elevated body mass index and caloric intake had increased risk, whereas those with elevated values for one of these factors but not the other experienced no increased risk. This finding suggests that energy balance may play a major role in pancreatic carcinogenesis. Diabetes mellitus was also a risk factor for pancreatic cancer, as well as a possible complication of the tumor. Our data are consistent with a key role for hyperinsulinemia in pancreatic carcinogenesis, particularly among non-diabetics with an elevated body mass index. A three-fold risk of pancreatic cancer among first-degree relatives of affected individuals was apparent. An increased risk also was associated with a family history of colon, endometrial, ovary, and breast cancer, suggesting a possible link to hereditary non-polyposis colon cancer. Our findings support a causal role for cigarette smoking in pancreatic carcinogenesis. Alcohol drinking at levels typically consumed by the general population of the United States did not appear to be a risk factor for pancreatic cancer, although heavy drinking may be related to risk, particularly in blacks.

A meta-analysis of bladder cancer and diesel exhaust exposure.

The aim of this study is to review and summarize the available epidemiologic studies of bladder cancer and occupational exposure to diesel exhaust. We retrieved relevant studies and abstracted their characteristics and results. We assessed the heterogeneity of the results to decide whether to perform a fixed-effects model meta-analysis. We identified 35 relevant studies. No overall meta-analysis was performed because of heterogeneity in results. Results of railroad workers (N = 14) suggested an increased occurrence of bladder cancer, but we did not conduct a meta-analysis. The summary relative risk (RR) among truck drivers was 1.17 (95% confidence interval [CI] = 1.06-1.29, 15 studies) and that among bus drivers was 1.33 (95% CI = 1.22-1.45, 10 studies). Ten studies considered diesel exhaust exposure based on a job exposure matrix or a similar approach; the summary RR for these studies was 1.13 (95% CI = 1.00-1.27). A positive dose-response relation was suggested by 10 of the 12 studies that provided relevant information. The summary RR for high diesel exposure was 1.44 (95% CI = 1.18-1.76). There was some evidence of publication bias, however, with a lack of small studies with null or negative results. Our review suggests that exposure to diesel exhaust may increase the occurrence of bladder cancer, but the effects of misclassification, publication bias, and confounding cannot be fully taken into account.

Occupational exposure to pesticides and pancreatic cancer.

BACKGROUND: An increased risk of exposure to pesticides for pancreatic cancer has been suggested in a number of epidemiologic studies. METHODS: Cases (N = 484), aged 30-79 years, were diagnosed in 1986-1989. Controls (N = 2,095) were a random sample of the general population. Information on usual occupation and potential confounding factors was obtained. A job-exposure matrix (JEM) approach was used to estimate the level of occupational exposure to pesticides. RESULTS: A significant trend in risk with increasing exposure level of pesticides was observed, with ORs of 1.3 and 1.4 for low and moderate/high exposure levels, respectively. Excess risks were found for occupational exposure to fungicides (OR = 1.5) and herbicides (OR = 1.6) in the moderate/high level after adjustment for potential confounding factors. An increased risk for insecticide exposure was disappeared after adjustment for fungicide and herbicide exposures. Results of our occupation-based analysis were consistent with those from the JEM-based analysis. CONCLUSIONS: Our results suggest that pesticides may increase risk of pancreatic cancer, and indicate the need for investigations that can evaluate risk by specific chemical exposures. Published 2001 Wiley-Liss, Inc.

Socioeconomic status and multiple myeloma among US blacks and whites.

OBJECTIVES: This study examined the relation between socioeconomic status (SES) and risk of multiple myeloma among Blacks and Whites in the United States. METHODS: This population-based case-control study included 573 cases (206 Blacks and 367 Whites) with new diagnoses of multiple myeloma identified between August 1, 1986, and April 30, 1989, and 2131 controls (967 Blacks and 1164 Whites) from 3 US geographic areas. Information on occupation, income, and education was obtained by personal interview. RESULTS: Inverse gradients in risk were associated with occupation-based SES, income, and education. Risks were significantly elevated for subjects in the lowest categories of occupation-based SES (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.16, 2.53), education (OR = 1.36, 95% CI = 1.06, 1.75), and income (OR = 1.43, 95% CI = 1.05, 1.93). Occupation-based low SES accounted for 37% of multiple myeloma in Blacks and 17% in Whites, as well as 49% of the excess incidence in Blacks. Low education and low income accounted for 17% and 28% of the excess incidence in Blacks, respectively. CONCLUSIONS: Our results indicate that the measured SES-related factors account for a substantial amount of the Black-White differential in multiple myeloma incidence.

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer.

In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9-1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer.

Occupational risk factors for pancreatic cancer: a case-control study based on death certificates from 24 U.S. states.

BACKGROUND: The relation between occupational exposure and pancreatic cancer is not well established. A population-based case-control study based on death certificates from 24 U.S. states was conducted to determine if occupations/industries or work-related exposures to solvents were associated with pancreatic cancer death. METHODS: The cases were 63,097 persons who died from pancreatic cancer occurring in the period 1984-1993. The controls were 252,386 persons who died from causes other than cancer in the same time period. RESULTS: Industries associated with significantly increased risk of pancreatic cancer included printing and paper manufacturing; chemical, petroleum, and related processing; transport, communication, and public service; wholesale and retail trades; and medical and other health-related services. Occupations associated with significantly increased risk included managerial, administrative, and other professional occupations; technical occupations; and sales, clerical, and other administrative support occupations. Potential exposures to formaldehyde and other solvents were assessed by using a job exposure matrix developed for this study. Occupational exposure to formaldehyde was associated with a moderately increased risk of pancreatic cancer, with ORs of 1.2, 1.2, 1.4 for subjects with low, medium, and high probabilities of exposure and 1.2, 1.2, and 1.1 for subjects with low, medium, and high intensity of exposure, respectively. CONCLUSIONS: The findings of this study did not suggest that industrial or occupational exposure is a major contributor to the etiology of pancreatic cancer. Further study may be needed to confirm the positive association between formaldehyde exposure and pancreatic cancer. Published 1999 Wiley-Liss, Inc.