Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

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

BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

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.

Changing trends of diseases in Eastern Europe: closing the gap.

One of the greatest challenges in Europe at the beginning of the 21st Century is the wide east-west health gap. In 2008, the difference in life expectancy between men in some Western European countries and Russia was 20 years. Whilst trends for life expectancy at birth have improved in many areas around the world, those for Russia, as well as those for some other former Soviet Union countries, have fluctuated greatly and have not shown signs of growth since the middle of the 20th Century. This problem is most acute in Russia and former Soviet Union countries, but is also far from being solved in the states that have made significant progress since 1990 and joined the European Union in the 21st Century. One of the priorities of the Polish presidency of the European Union, which began in July 2011, is the call for a European solidarity for health that could help to close the health gap dividing Europe.

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.

Human papillomavirus infection in women with and without cervical cancer in Warsaw, Poland.

Cervical cancer incidence and mortality in Poland is among the highest in Europe. To investigate infection with different human papillomaviruses (HPV) in Warsaw, Poland, we obtained cervical cell specimens from 834 women aged 18-59 years from the general population, and 88 cervical cancers. DNA of 44 HPV types was detected using a GP5+/6+-based PCR assay. HPV prevalence was 16.6% in the general female population, being highest (24.2%) in women aged 25-34 years, notably among unmarried women (37.3%). HPV prevalence fell to 8.6% at ages 55-59. High-risk HPV prevalence was 11.3%, with HPV16 being the most common type (3.7%). All but one cervical cancer were high-risk HPV-positive, although the importance of HPV16 (73%) was much greater, and multiple infections fewer (1%), than among HPV-positive women in the general female population. In summary, we report a relatively high burden of HPV infection in Warsaw, Poland, where 79% of cervical cancers are theoretically preventable by HPV16/18 vaccines.

Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon.

BACKGROUND: For unknown reasons, the age-standardized incidence of testicular cancer has shown a rapid increase in virtually all countries (mostly Western) studied. For populations with a sufficiently long period of cancer registration, this development can be traced back to the first half of this century. PURPOSE: By evaluating data from six countries with long periods of cancer registration (Denmark, Norway, Sweden, the former German Democratic Republic [East Germany], Finland, and Poland), we sought to determine whether the increase in testicular cancer risk follows a birth cohort pattern and, if so, to quantify and compare any birth cohort effects. METHODS: A total of 30,908 incident cases of testicular cancer, diagnosed from 1945 through 1989 in men who were 20-84 years of age, were identified in population-based cancer registries in the six countries. In addition to performing simple trend analyses, we fitted several Poisson regression models (with the explanatory variables age, time period [calendar time], and birth cohort) to the data. Individual models were estimated by the maximum likelihood method. RESULTS: The age-standardized incidence of testicular cancer was found to vary among the six populations and, on the basis of total registration data, increased annually at rates ranging from 2.3% (in Sweden) to 5.2% (in East Germany). A comparison of several regression models indicated that birth cohort was a stronger determinant of testicular cancer risk than was calendar time for all six populations. Within each population, little variation in testicular cancer risk was observed for men born between 1880 and 1920; thereafter, the risk began to increase. Among men born in Denmark, Norway, and Sweden between 1930 and 1945 (the period encompassing the Second World War), the increasing trend in risk was interrupted (i.e., a leveling in risk occurred). After 1945, an uninterrupted increase in risk was observed for all six populations. With men born around 1905 as the reference group, the relative risk of testicular cancer for those born around 1965 varied from 3.9 (95% confidence interval [CI] = 2.7-5.6) in Sweden to 11.4 (95% CI = 8.3-15.5) in East Germany. CONCLUSIONS AND IMPLICATIONS: The increasing trend in testicular cancer risk observed for these six populations follows a birth cohort pattern. This distinct risk pattern provides a framework for the identification of specific etiologic factors.

Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer.

BACKGROUND: There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. PURPOSE: Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. METHODS: A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. RESULTS: After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. CONCLUSIONS: These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

Occupation and risk of stomach cancer in Poland.

BACKGROUND: In spite of the dramatic decline in the incidence of stomach cancer in the twentieth century, Poland has one of the highest rates in the world. AIMS: To evaluate the risk of stomach cancer by grouped occupations and industries, as well as by some specific occupational exposures. METHODS: Cases (n = 443) were newly diagnosed with stomach adenocarcinomas between 1994 and 1996. Controls (n = 479) were randomly selected from the general population in Warsaw. RESULTS: Only a few occupations and industries were associated with significantly increased risks of stomach cancer. The most suggestive finding was for work in the leather goods industry. Risk was also significantly increased among men working in fabricated metal production and among women ever employed as managers and governmental officials. Men ever employed as teaching professionals and women employed as technical and science professionals had significantly decreased risks of stomach cancer. Among men, a significant positive trend in risk with duration of employment was observed for work in the leather industry and special trade construction. No significantly increased risks were observed for specific exposures assessed by a job-exposure matrix or by self-reports. However among men there were non-significantly increased risks with 10 or more years exposure to asbestos, metal dust, and nitrosamines assessed by a job-exposure matrix. CONCLUSIONS: Employment in the leather goods industry, special trade construction, and metal fabrication was associated with an increased risk of stomach cancer among men. However, there were only weak associations with specific exposures. Occupational exposures do not contribute substantially to the high rates of stomach cancer in Poland.

Glutathione S-transferase genotypes and stomach cancer in a population-based case-control study in Warsaw, Poland.

Glutathione S-transferases are important in the detoxification of a wide range of human carcinogens. Previous studies have shown inconsistent associations between the GSTT1 and GSTM1 null genotypes and stomach cancer risk. We investigated the relationship between these and related genotypes and stomach cancer risk in a population-based case-control study in Warsaw, Poland, where stomach cancer incidence and mortality rates are among the highest in Europe. DNA from blood samples was available for 304 stomach cancer patients and 427 control subjects. We observed a 1.48-fold increased risk for stomach cancer (95% confidence interval 0.97-2.25) in patients with the GSTT1 null genotype but no evidence of increased risk associated with the GSTM1, GSTM3 or GSTP1 genotypes. Furthermore, the stomach cancer risk associated with the GSTT1 null genotype varied by age at diagnosis, with odds ratios of 3.85, 1.91, 1.78 and 0.59 for those diagnosed at ages less than 50, 50-59, 60-69 and 70 years or older, respectively (P trend = 0.01). This was due to a shift in the GSTT1 genotype distribution across age groups among stomach cancer patients only. These results suggest that the GSTT1 null genotype may be associated with increased risk of stomach cancer.

Cancer mortality among Polish migrants to Australia.

This paper investigates the risk of cancer in Polish migrants to Australia, and compares the results with earlier studies, as well as with results of studies of Polish migrants in other countries. Poisson regression models were used to estimate the risk of death in Polish migrants, relative to the Australia-born, as well as the relative risk of cancer in Poland compared to the Australia-born. In migrant males, a significantly lower risk was found for oral cavity and pharynx, larynx, melanoma, prostate and Hodgkin's disease, while a significantly elevated risk was found for stomach, liver, pancreas, kidney and thyroid gland. In migrant females, a risk significantly lower than in Australian-born individuals was found for oral cavity, colon, melanoma, breast and non-Hodgkin's lymphoma. Relative risk significantly higher than in Australia-born was detected for stomach, gall bladder, pancreas, cervix uteri, nervous system and thyroid gland. For some of these cancers, the risk in migrants approximates to that of the Australia-born with increasing duration of stay. Thus, there are progressive increases in risk for colon cancer in males, and breast cancer and melanoma in females, and decreases in risk for stomach and bladder cancers in males, and uterine cancers in females.

The anti-smoking climate in EU countries and Poland.

BACKGROUND: In the fall of 1998, 9095 smokers above 18 years, were interviewed about their smoking behaviour and knowledge and attitudes relating to the smoking. The survey (S) was conducted for the Cancer Commission of the EU and sponsored by SmithKline Beecham. An anti-smoking thermometer that is intended to assess the anti-smoking climate (ASC) in each EU country plus Poland was created. In doing so country owners of the S were asked to choose and rank the five questions in the S they thought best reflected the ASC. The five questions chosen were--smoking is a major cause of death and disease, want to stop smoking, governments should do more, ever made a serious quit attempt and smoke free areas should be provided. METHOD: The smokers comprised a representative sample of smoking cigarette per day, vis-a-vis age, sex and rural or urban area. Face to face interviews were conducted using a semi-structured questionnaire. RESULTS: Poland had the most developed ASC, 368 points, followed closely by Sweden 358. In the bottom were Germany 266 and Austria 258. Large differences were noted on willingness to quit; from the 85% in Sweden to Italy 37%. CONCLUSION: The ASC varies considerably within EU and measures to reduce the death and disease from smoking should be tailored to the situation in each country.

Descriptive epidemiology of gall-bladder cancer in Europe.

Trends in mortality from cancer of the gall-bladder and bile ducts over the period 1965-1989 were analysed for 25 European countries on the basis of official death certifications from the World Health Organization databank. A high-mortality area--i.e. with overall death certification rates, world standard, around or over 2/100,000 men and 4/100,000 women in 1985-1989--was identified in Germany and the surrounding central European countries (Austria, Czechoslovakia, Hungary and Poland). The highest rates were in Hungary (3.9/100,000 men and 7.4/100,000 women). During the two decades considered, rates increased in Czechoslovakia and Hungary, remained stable in Poland and declined in Austria and Germany. Intermediate-mortality areas included Scandinavian countries (except Norway) and Switzerland: their rates in the late 1980s were between 1.5 and 2.5/100,000 men and between 2.2 and 4.2/100,000 women. Mortality increased in Finland and Sweden, declined in the Netherlands and Switzerland, and did not change consistently in Denmark. Low-mortality countries (i.e. with rates in 1985-1989 below 2.0/100,000 men and 2.5/100,000 women) included Belgium, France, Britain, Ireland, Norway, Bulgaria and Mediterranean countries. Over the last two decades, certification rates declined in Bulgaria and Great Britain, but increased in all other countries. The ratio between the countries with the highest and lowest gall-bladder cancer mortality rates declined from 21 to 12 in women, although they remained stable around 10 for men. The pattern was similar when analysis was restricted to truncated rates from patients aged between 35 and 64 years. These trends, and particularly the exceedingly high rates in central Europe, the low rates in Mediterranean countries and the low and declining rates in Britain and Ireland are discussed in terms of known (cholelithiasis) or potential (dietary) factors in gall-bladder cancer aetiology, and of trends in cholecystectomy rates.

Smoking, alcohol, diet, dentition and sexual practices in the epidemiology of oral cancer in Poland.

The effect of smoking, drinking, diet, dental care and sexual habits on the risk of oral and pharyngeal cancer was investigated in a case-control study conducted in Warsaw, Poland. The study comprised 122 patients (including 44 females) aged 23-80 years with histologically confirmed cancer of oral cavity and pharynx. Controls were 124 subjects (including 52 females) admitted to the hospital for different non-neoplastic conditions unrelated to tobacco and alcohol consumption, with frequency matched to cases by age and sex. Smoking and drinking were strongly associated with an increased risk of oral cancer. Among consumers of both products, risks of oral cancer tended to combine in a multiplicative fashion and were increased more than 14-fold among those who consumed more than 15 cigarettes and seven or more drinks per day. Cessation of smoking was associated with reduced risk of this cancer. The risks varied by type of cigarettes smoked, being lower among those consuming filtered cigarettes only (OR = 1.6) than nonfilter (OR = 6.5) or mixed (OR = 4.2) cigarettes. High fruit intake was associated with significantly decreased risk (OR = 0.4) with the strongest significant inverse association found for fruit juices and citrus fruits ( < 0.01). After adjustment for tobacco smoking and alcohol drinking, poor dentition as evidenced by missing teeth, frequency of dental check-ups and frequency of teeth brushing emerged as a strong risk factor. Number of missing teeth and frequency of dental check-ups and frequency of tooth brushing showed increased ORs of 9.8, 11.9 and 3.2, respectively. Denture wearing did not affect oral cancer risk. No differences were detected in sexual practices (including oral sex and intercourse with prostitutes). In terms of attributable risk, smoking accounted for 57% of oral cancer cases in Poland, alcohol for 31% and low fruit intake for 12%. Attributable risks for low frequency of tooth brushing and dental check-ups were 56% and 47%, respectively. In conclusion, smoking and drinking cessation and increase of fresh fruit intake are likely to be effective preventive measures against oral cancer. These findings indicate also that poor oral hygiene may be an independent risk factor.

Family history and risk of stomach cancer in Warsaw, Poland.

In a population-based case-control study of stomach cancer conducted in Warsaw, Poland, 464 cases and 480 controls were interviewed to evaluate the role of family history and other risk factors. A greater than threefold increase in risk was associated with a history of stomach cancer in a first degree relative (OR = 3.5; 95% Cl = 2.0-6.2), but no excess risk was seen with other forms of cancer. The risk associated with familial occurrence was not significantly modified by gender, age or ABO blood type, and did not vary with Laurén histologic classification. Our findings add to evidence for a familial predisposition to both diffuse and intestinal types of gastric cancer. Further studies are needed to identify the susceptibility genes and environmental exposures that may account for the familial tendency to stomach cancer.

Acquired enzymopathy of erythrocyte glucose-6-phosphate dehydrogenase in acute viral hepatitis.

Erythrocyte glucose-6-phosphate dehydrogenase from patients with acute viral hepatitis has been purified and characterized. The enzyme showed decreased activity (relative to protein), reduced affinity for glucose 6-phosphate and was inactivated at 45 degrees C or at low pH values. The activity and properties of normal erythrocyte enzyme, incubated in vitro with blood plasma of patients, showed a similar pattern of modifications. Incubation with bilirubin affected the enzyme stability, but not its activity or affinity for substrate.