Search

Background: The Baltic countries-Lithuania, Latvia and Estonia-are characterized by a high rate of fully alcohol-attributable mortality, compared with Poland. Alcohol control policy measures implemented since 2001 in the Baltic countries included a restriction on availability and an increase in excise taxation, among others. The aim of the current study was to evaluate the relationship between alcohol control policy implementation and alcohol-attributable mortality in the Baltic countries and Poland., Methods: Alcohol-attributable mortality data for 2001-2020 was defined by codes 100% alcohol-attributable for persons aged 15 years and older in the Baltic countries and Poland. Alcohol control policies implemented between 2001 and 2020 were identified, and their impact on alcohol-attributable mortality was evaluated using an interrupted time-series methodology by employing a generalized additive model., Results: Alcohol-attributable mortality was significantly higher in the Baltic countries, compared with Poland, for both males and females. In the final reduced model, alcohol control policy significantly reduced male alcohol-attributable mortality by 7.60% in the 12 months post-policy implementation. For females, the alcohol control policy mean-shift effect was higher, resulting in a significant reduction of alcohol-attributable mortality by 10.77% in the 12 months post-policy implementation. The interaction effects of countries and policy tested in the full model were not statistically significant, which indicated that the impact of alcohol control policy on alcohol-attributable mortality did not differ across countries for both males and females., Conclusions: Based on the findings of the current study, alcohol control policy in the form of reduced availability and increased taxation was associated with a reduction in alcohol-attributable mortality among both males and females., (© 2023. The Author(s).)

Background and Aims: The addictive potential of electronic cigarettes (e-cigarettes) remains to be fully understood. We identified patterns and correlates of perceived addiction to e-cigarettes and perceived addictiveness of e-cigarettes relative to tobacco cigarettes (relative addictiveness) in dual users as well as exclusive e-cigarette users., Design, Setting and Participants: Observational study using cross-sectional survey data from England (2016) from the International Tobacco Control Project (ITC) Four Country Smoking and Vaping (4CV) survey. The study comprised 832 current e-cigarette users who had been vaping for at least 4 months., Measurements: Perceived addiction to e-cigarettes and relative addictiveness of e-cigarettes were examined. Socio-demographic factors were age, gender and education; markers of addiction included urge to vape, time to first vape after waking and nicotine strength used; vaping and smoking characteristics included frequency and duration of e-cigarette use, intention to quit, adjustable power or temperature, enjoyment, satisfaction relative to tobacco cigarettes and tobacco cigarette smoking status., Findings: A total of 17% of participants reported feeling very addicted to e-cigarettes, while 40% considered e-cigarettes equally/more addictive than tobacco cigarettes. Those who felt very addicted had higher odds of regarding e-cigarettes as more addictive than tobacco cigarettes (odds ratio 3.4, 95% confidence interval 2.3-5.1). All markers of addiction, daily use and enjoyment were associated with higher perceived addiction, whereas time to first vape after waking, daily vaping and perceiving vaping as less satisfying than smoking were associated with relative addictiveness., Conclusions: Markers of addiction to e-cigarettes appear to correspond with perceived addiction to e-cigarettes, suggesting that self-reported perceived addiction might serve as an indicator of addiction. Prevalence both of markers of addiction and perceived addiction were comparatively low overall, suggesting a limited but relevant addictive potential of e-cigarettes. Additionally, positive and negative reinforcement, reflected here by enjoyment and relative satisfaction, might play a role in e-cigarette addiction., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies., Aim: To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy., Methods: We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models., Results: Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed <2 years before pancreatic cancer diagnosis and 1.11 (95% confidence interval, 0.96-1.29) when ≥2 years elapsed. The pooled odds ratio was 1.64 (95% confidence interval, 1.43-1.89) for patients who underwent cholecystectomy, as compared to those without cholecystectomy. The odds ratio was 7.00 (95% confidence interval, 4.13-11.86) for a surgery <2 years before pancreatic cancer diagnosis and 1.28 (95% confidence interval, 1.08-1.53) for a surgery ≥2 years before., Conclusions: There appears to be no long-term effect of gallbladder disease on pancreatic cancer risk, and at most a modest one for cholecystectomy. The strong short-term association can be explained by diagnostic bias and reverse causation.

Background: New oral treatments with very high cure rates have the potential to revolutionize global management of hepatitis C virus (HCV), but population-based data on HCV infection are missing in many low and middle-income countries (LMIC)., Methods: Between 2004 and 2009, dried blood spots were collected from age-stratified female population samples of 9 countries: China, Mongolia, Poland, Guinea, Nepal, Pakistan, Algeria, Georgia and Iran. HCV antibodies were detected by a multiplex serology assay using bead-based technology., Results: Crude HCV prevalence ranged from 17.4% in Mongolia to 0.0% in Iran. In a pooled model adjusted by age and country, in which associations with risk factors were not statistically heterogeneous across countries, the only significant determinants of HCV positivity were age (prevalence ratio for ≥45 versus <35 years = 2.84, 95%CI 2.18-3.71) and parity (parous versus nulliparous = 1.73, 95%CI 1.02-2.93). Statistically significant increases in HCV positivity by age, but not parity, were seen in each of the three countries with the highest number of HCV infections: Mongolia, Pakistan, China. There were no associations with sexual partners nor HPV infection. HCV prevalence in women aged ≥45 years correlated well with recent estimates of female HCV-related liver cancer incidence, with the slight exception of Pakistan, which showed a higher HCV prevalence (5.2%) than expected., Conclusions: HCV prevalence varies enormously in women worldwide. Medical interventions/hospitalizations linked to childbirth may have represented a route of HCV transmission, but not sexual intercourse. Combining dried blood spot collection with high-throughput HCV assays can facilitate seroepidemiological studies in LMIC where data is otherwise scarce.

Objectives: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC)., Methods: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates., Results: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84)., Conclusions: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary., Competing Interests: The authors have no conflicts of interest to report

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer., (Copyright © 2015 International Agency for Research on Cancer. Published by Elsevier Ltd. All rights reserved.)

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., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

Background: Despite the high global burden of diseases caused by tobacco, valid and comparable prevalence data for patterns of adult tobacco use and factors influencing use are absent for many low-income and middle-income countries. We assess these patterns through analysis of data from the Global Adult Tobacco Survey (GATS)., Methods: Between Oct 1, 2008, and March 15, 2010, GATS used nationally representative household surveys with comparable methods to obtain relevant information from individuals aged 15 years or older in 14 low-income and middle-income countries (Bangladesh, Brazil, China, Egypt, India, Mexico, Philippines, Poland, Russia, Thailand, Turkey, Ukraine, Uruguay, and Vietnam). We compared weighted point estimates and 95% CIs of tobacco use between these 14 countries and with data from the 2008 UK General Lifestyle Survey and the 2006-07 US Tobacco Use Supplement to the Current Population Survey. All these surveys had cross-sectional study designs., Findings: In countries participating in GATS, 48·6% (95% CI 47·6-49·6) of men and 11·3% (10·7-12·0) of women were tobacco users. 40·7% of men (ranging from 21·6% in Brazil to 60·2% in Russia) and 5·0% of women (0·5% in Egypt to 24·4% in Poland) in GATS countries smoked a tobacco product. Manufactured cigarettes were favoured by most smokers (82%) overall, but smokeless tobacco and bidis were commonly used in India and Bangladesh. For individuals who had ever smoked daily, women aged 55-64 years at the time of the survey began smoking at an older age than did equivalently aged men in most GATS countries. However, those individuals who had ever smoked daily and were aged 25-34-years when surveyed started to do so at much the same age in both sexes. Quit ratios were very low (<20% overall) in China, India, Russia, Egypt, and Bangladesh., Interpretation: The first wave of GATS showed high rates of smoking in men, early initiation of smoking in women, and low quit ratios, reinforcing the view that efforts to prevent initiation and promote cessation of tobacco use are needed to reduce associated morbidity and mortality., Funding: Bloomberg Philanthropies' Initiative to Reduce Tobacco Use, Bill and Melinda Gates Foundation, Brazilian and Indian Governments., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

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., (Copyright © 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

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.

Background: Although most cardiovascular disease occurs in low-income and middle-income countries, little is known about the use of effective secondary prevention medications in these communities. We aimed to assess use of proven effective secondary preventive drugs (antiplatelet drugs, β blockers, angiotensin-converting-enzyme [ACE] inhibitors or angiotensin-receptor blockers [ARBs], and statins) in individuals with a history of coronary heart disease or stroke., Methods: In the Prospective Urban Rural Epidemiological (PURE) study, we recruited individuals aged 35-70 years from rural and urban communities in countries at various stages of economic development. We assessed rates of previous cardiovascular disease (coronary heart disease or stroke) and use of proven effective secondary preventive drugs and blood-pressure-lowering drugs with standardised questionnaires, which were completed by telephone interviews, household visits, or on patient's presentation to clinics. We report estimates of drug use at national, community, and individual levels., Findings: We enrolled 153,996 adults from 628 urban and rural communities in countries with incomes classified as high (three countries), upper-middle (seven), lower-middle (three), or low (four) between January, 2003, and December, 2009. 5650 participants had a self-reported coronary heart disease event (median 5·0 years previously [IQR 2·0-10·0]) and 2292 had stroke (4·0 years previously [2·0-8·0]). Overall, few individuals with cardiovascular disease took antiplatelet drugs (25·3%), β blockers (17·4%), ACE inhibitors or ARBs (19·5%), or statins (14·6%). Use was highest in high-income countries (antiplatelet drugs 62·0%, β blockers 40·0%, ACE inhibitors or ARBs 49·8%, and statins 66·5%), lowest in low-income countries (8·8%, 9·7%, 5·2%, and 3·3%, respectively), and decreased in line with reduction of country economic status (p(trend)<0·0001 for every drug type). Fewest patients received no drugs in high-income countries (11·2%), compared with 45·1% in upper middle-income countries, 69·3% in lower middle-income countries, and 80·2% in low-income countries. Drug use was higher in urban than rural areas (antiplatelet drugs 28·7% urban vs 21·3% rural, β blockers 23·5%vs 15·6%, ACE inhibitors or ARBs 22·8%vs 15·5%, and statins 19·9%vs 11·6%; all p<0·0001), with greatest variation in poorest countries (p(interaction)<0·0001 for urban vs rural differences by country economic status). Country-level factors (eg, economic status) affected rates of drug use more than did individual-level factors (eg, age, sex, education, smoking status, body-mass index, and hypertension and diabetes statuses)., Interpretation: Because use of secondary prevention medications is low worldwide-especially in low-income countries and rural areas-systematic approaches are needed to improve the long-term use of basic, inexpensive, and effective drugs., Funding: Full funding sources listed at end of paper (see Acknowledgments)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Cytisine, a partial agonist that binds with high affinity to the α(4)β(2) nicotinic acetylcholine receptor, is a low-cost treatment that may be effective in aiding smoking cessation. This study assessed the efficacy and safety of cytisine as compared with placebo., Methods: We conducted a single-center, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive cytisine or matching placebo for 25 days; participants in both groups received a minimal amount of counseling during the study. The primary outcome measure was sustained, biochemically verified smoking abstinence for 12 months after the end of treatment. Of 1542 adult smokers screened, 740 were enrolled and 370 were randomly assigned to each study group., Results: The rate of sustained 12-month abstinence was 8.4% (31 participants) in the cytisine group as compared with 2.4% (9 participants) in the placebo group (difference, 6.0 percentage points; 95% confidence interval [CI], 2.7 to 9.2; P=0.001). The 7-day point prevalence for abstinence at the 12-month follow-up was 13.2% in the cytisine group versus 7.3% in the placebo group (P=0.01). Gastrointestinal adverse events were reported more frequently in the cytisine group (difference, 5.7 percentage points; 95% CI, 1.2 to 10.2)., Conclusions: In this single-center study, cytisine was more effective than placebo for smoking cessation. The lower price of cytisine as compared with that of other pharmacotherapies for smoking cessation may make it an affordable treatment to advance smoking cessation globally.

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.

Global hypomethylation has been shown to increase genome instability potentially leading to increased cancer risk. We determined whether global methylation in blood leukocyte DNA was associated with gastric cancer in a population-based study on 302 gastric cancer cases and 421 age- and sex-matched controls in Warsaw, Poland, between 1994 and 1996. Using PCR-pyrosequencing, we analyzed methylation levels of Alu and LINE-1, 2 CG-rich repetitive elements, to measure global methylation levels. Gastric cancer risk was highest among those with lowest level of methylation in either Alu (OR = 1.3, 95% CI = 0.9-1.9) or LINE-1 (OR = 1.4, 95% CI = 0.9-2.0) relative to those with the highest levels, although the trends were not statistically significant. For Alu, the association was stronger among those aged 70 or older (OR = 2.6, 95% CI = 1.3-5.5, p for interaction = 0.02). We did not observe meaningful differences in the associations by other risk factors and polymorphisms examined. For LINE-1, the association tended to be stronger among individuals with a family history of cancer (OR = 3.1, 95% CI = 1.4-7.0, p for interaction = 0.01), current alcohol drinkers (OR = 1.9, 95% CI = 1.0-3.6, p for interaction = 0.05), current smokers (OR = 2.3, 95% CI = 1.1-4.6, p for interaction = 0.02), those who rarely or never consumed fruit (OR = 3.1, 95% CI = 1.2-8.1, p for interaction = 0.03), CC carriers for the MTRR Ex5+123C>T polymorphism (OR = 2.3, 95% CI = 1.2-4.4, p for interaction = 0.01) and TT carriers for the MTRR Ex15+572T>C polymorphism (OR = 1.7, 95% CI = 1.0-2.8, p for interaction = 0.06). The association was not different by sex, Helicobacter pylori infection, intake of folate, vitamin B6 and total protein and the remaining polymorphisms examined. Our results indicate that interactions between blood leukocyte DNA hypomethylation and host characteristics may determine gastric cancer risk.

Background: It has been shown that the prevention of multicausal diseases such as heart attack (at an individual level) should be guided by absolute risks rather than by the level of risk factors. Here, we show that an analogous argument should form the basis of population-level prevention., Methods: Estimates of age- and sex-specific means and standard deviations for systolic blood pressures and blood cholesterol concentrations and for deaths assigned to all vascular causes in 2002 were obtained from the World Health Organization for 25 current member states of the European Union, for the ages 30-69 years. Predicted effects of 5 mmHg reductions in mean systolic blood pressures and 0.5 mmol l(-1) reductions in mean total blood cholesterol concentrations on deaths and years of life lost (YLL) per 100,000 person-years from vascular diseases were modelled using proportional risk coefficients from meta-analyses of cohort studies and randomized controlled trials., Results: Potential absolute benefits were strongly positively associated with current levels of absolute mortality risk: in the case of systolic blood pressure, predicted vascular deaths averted in the highest risk populations (Romania, Bulgaria) were over five times higher than in the lowest risk populations (Spain, France). Potential benefits were only weakly related to existing levels of the risk factor of interest., Conclusions: High-risk populations should give the highest priority to achieving favourable shifts in all modifiable risk factors. Irrespective of the level of any particular risk factor, the rewards will be greatest in these populations.

We conducted a population-based case-control study on the relation of menstrual and reproductive factors and hormone use with pancreatic cancer risk among female participants of the SEARCH program study. We evaluated 367 cases of ductal adenocarcinoma and 821 controls for associations between pancreatic cancer and age at menarche, age at menopause, number of pregnancies, exogenous hormone use, and history of gynaecologic surgery. Among directly interviewed and proxy participants, we found a statistically significant association for having age of menarche at 11 years or younger compared with menarche at ages 12-13 years (OR = 1.8, 95% CI = 1.1-3.1). This result was consistent, but not statistically significant, among three of the four studies analyzed, and when the data were analyzed separately by response status (direct vs. proxy interviews). No other menstrual or reproductive factors were associated with pancreatic cancer risk in this study. In conclusion, earlier age at menarche may be weakly associated with pancreatic cancer, but it seems unlikely that menstrual and reproductive factors play more than only a minor role in pancreatic cancer. Additional analyses in large prospective study populations and in pooled studies may help to clarify remaining inconsistencies.

Telomere length reflects lifetime cumulative oxidative stress from environmental exposures, such as cigarette smoking and chronic inflammation. Shortened telomere length is thought to cause genomic instability and has been associated with several cancers. We examined the association of telomere length in peripheral leukocyte DNA with gastric cancer risk as well as potential confounding factors and risk modifiers for telomere length-related risk. In a population-based study of gastric cancer conducted in a high-risk population in Warsaw, Poland, between 1994 and 1996, we measured relative telomere length in 300 cases and 416 age- and gender-matched controls using quantitative real-time PCR. Among controls, telomeres were significantly shorter in association with aging (P < 0.001), increasing pack-years of cigarette smoking (P = 0.02), decreasing fruit intake (P = 0.04), and Helicobacter pylori positivity (P = 0.03). Gastric cancer cases had significantly shorter telomere length (mean +/- SD relative telomere length, 1.25 +/- 0.34) than controls (1.34 +/- 0.35; P = 0.0008). Gastric cancer risk doubled [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.33-3.13] among subjects in the shortest compared with the highest quartile of telomere length (P(trend) < 0.001). Telomere length-associated risks were higher among individuals with the lowest risk profile, those H. pylori-negative (OR, 5.45; 95% CI, 2.10-14.1), nonsmokers (OR, 3.07; 95% CI, 1.71-5.51), and individuals with high intake of fruits (OR, 2.43; 95% CI, 1.46-4.05) or vegetables (OR, 2.39; 95% CI, 1.51-3.81). Our results suggest that telomere length in peripheral leukocyte DNA was associated with H. pylori positivity, cigarette smoking, and dietary fruit intake. Shortened telomeres increased gastric cancer risk in this high-risk Polish population.

Background: The research aimed to study the quality of cheap alcohol products in Poland. These included unrecorded alcohols (i.e., home-produced or illegally imported), estimated to constitute more than 25% of total consumption and fruit wines., Methods: A sample of alcohol products (n = 52) was collected from local markets and chemical analyses were conducted. The parameters studied were alcoholic strength, volatiles (methanol, acetaldehyde, and higher alcohols), ethyl carbamate, inorganic elements, and food additives including preservatives, colors, and sweeteners. The compositions of the beverages were then toxicologically evaluated using international standards., Results: With the exception of 1 fortified wine, the unrecorded alcohols were home-produced fruit-derived spirits (moonshine) and spirits imported from other countries. We did not detect any nonbeverage surrogate alcohol. The unrecorded spirits contained, on average, 45% vol of alcohol. However, some products with considerably higher alcoholic strengths were found (up to 85% vol) with no labeling of the content on the bottles. These products may cause more pronounced detrimental health effects (e.g., liver cirrhosis, injuries, some forms of malignant neoplasms, alcohol use disorders, and cardiovascular disease) than will commercial beverages, especially as the consumer may be unaware of the alcohol content consumed. Fruit wines containing between 9.5 and 12.2% vol alcohol showed problems in terms of their additive content and their labeling (e.g., sulfites, sorbic acid, saccharin, and artificial colors) and should be subjected to stricter control. Regarding the other components investigated, the suspected human carcinogens, acetaldehyde and ethyl carbamate, were found at levels relevant to public health concerns. While acetaldehyde is a typical constituent of fermented beverages, ethyl carbamate was found only in home-produced unrecorded alcohols derived from stone fruits with levels significantly above international guidelines., Conclusions: The contamination of unrecorded alcohols with ethyl carbamate should be analyzed in a larger sample that also should include legal alcoholic beverages. Furthermore, the impacts of unrecorded alcohol on the health of people with lower socioeconomic status should be studied in detail. Overall, given the extent of the alcohol-attributable disease burden in Poland, the highest priority should be given to the problem of ethanol and its very high content in unrecorded alcohol products.

Higher ascorbic acid consumption is associated with a reduced risk of gastric cancer in numerous epidemiologic studies. We investigated whether single nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2--genes that encode key ascorbic acid transport proteins--affect gastric cancer risk in 279 incident cases and 414 age- and gender-matched controls drawn from a population-based case-control study in Poland. Compared to subjects who were homozygous for the common G allele of the SLC23A2 SNP rs12479919, carriers of the AA genotype had a 41% lower risk of gastric cancer [odds ratio (OR)=0.59, 95% confidence interval (CI): 0.36-0.95; P trend=0.06]. A haplotype that contained the common allele of the rs6139591, rs2681116 and rs14147458 SNPs in SLC23A2 was also significantly inversely associated with gastric malignancy. No other polymorphisms in either gene were related to risk, and there was no effect modification by ascorbic acid intake. These findings suggest that genetic variation in SLC23A2 impacts gastric cancer risk, although confirmation in other studies is required.

Androgens and estrogens may play a role in gastric cancer etiology. To investigate the association of gastric cancer with single-nucleotide polymorphisms (SNPs) in six genes (COMT, CYP1B1, CYP17A1, CYP19A1, HSD17B1 and SHBG) involved in estrogen and androgen synthesis and metabolism, 58 haplotype-tagging SNPs were genotyped in 295 gastric cancer cases and 415 controls from a population-based study in Poland. We assessed differences in haplotype frequency between cases and controls using a global score test and calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for individual haplotypes using logistic regression. We found associations in one linkage disequilibrium (LD) block containing the 3' untranslated region of COMT (rs9332377, rs165728, rs165849 and rs1110478), global score test (df = 4, P = 0.033). Relative to the most frequent GATA haplotype, the GATG haplotype was associated with statistically significant increased gastric cancer risk (OR = 1.50, 95% CI: 1.06-2.12; false discovery rate (FDR) value = 0.459) and the AACA haplotype with borderline increased risk (OR = 1.36, 95% CI = 1.00-1.85; FDR = 0.50). We also found associations for the LD block containing part of the SHBG coding region (rs6258, rs6259, rs2955617, rs1641544 and rs1641537). The CACCC haplotype was associated with statistically significant lower gastric cancer risk relative to the referent CGACC haplotype (OR = 0.55, 95% CI = 0.34-0.90; FDR = 0.459), but the overall score test was statistically non-significant. No other statistically significant associations were observed. In summary, we found possible associations between gastric cancer and polymorphisms in COMT, involved in estrogen inactivation, and SHBG, a modulator of hormone bioavailability. These findings should be interpreted cautiously until replicated in other studies.

Background: This study examined two main hypotheses: a) Polish immigrants' smoking estimates are greater than their Irish counterparts (b) Polish immigrants purchasing cigarettes from Poland smoke "heavier" (>/= 20 cigarettes a day) when compared to those purchasing cigarettes from Ireland. The study also set out to identify significant predictors of 'current' smoking (some days and everyday) among the Polish immigrants., Methods: Dublin residents of Polish origin (n = 1,545) completed a previously validated Polish questionnaire in response to an advertisement in a local Polish lifestyle magazine over 5 weekends (July-August, 2007). The Office of Tobacco Control telephone-based monthly survey data were analyzed for the Irish population in Dublin for the same period (n = 484)., Results: Age-sex adjusted smoking estimates were: 47.6% (95% Confidence Interval [CI]: 47.3%; 48.0%) among the Poles and 27.8% (95% CI: 27.2%; 28.4%) among the general Irish population (p < 0.001). Of the 57% of smokers (n = 345/606) who purchased cigarettes solely from Poland and the 33% (n = 198/606) who purchased only from Ireland, 42.6% (n = 147/345) and 41.4% (n = 82/198) were "heavy" smokers, respectively (p = 0.79). Employment (Odds Ratio [OR]: 2.89; 95% CI: 1.25-6.69), lower education (OR: 3.76; 95%CI: 2.46-5.74), and a longer stay in Ireland (>24 months) were significant predictors of current smoking among the Poles. An objective validation of the self-reported smoking history of a randomly selected sub-sample immigrant group, using expired carbon monoxide (CO) measurements, showed a highly significant correlation coefficient (r = 0.64) of expired CO levels with the reported number of cigarettes consumed (p < 0.0001)., Conclusion: Polish immigrants' smoking estimates are higher than their Irish counterparts, and particularly if employed, with only primary-level education, and are overseas >2 years.

Host immune responses are known determinants of gastric cancer susceptibility. We previously reported an increased gastric cancer risk associated with common variants of several T helper type 1 (Th1) cytokine genes in a population-based case-control study in Warsaw, Poland. In the present study, we augmented our investigation to include additional Th1 genes as well as key genes in the Th2 and Th3 pathways. Analysis of 378 cases and 435 age- and sex-matched controls revealed associations for polymorphisms in the Th1 IL7R gene and one polymorphism in the Th2 IL5 gene. The odd ratios (ORs) for IL7R rs1494555 were 1.4 [95% confidence interval (CI), 1.0-1.9] for A/G and 1.5 (95% CI, 1.0-2.4) for G/G carriers relative to A/A carriers (P = 0.04). The ORs for IL5 rs2069812 were 0.9 (95% CI, 0.7-1.3) for C/T and 0.6 (95% CI, 0.3-1.0) T/T carriers compared with C/C carriers (P = 0.03). These results suggest that IL5 rs2069812 and IL7R rs1389832, rs1494556 and rs1494555 polymorphisms may contribute to gastric cancer etiology.

Objective: To evaluate the strength of the evidence provided by epidemiological literature investigating drinking pattern as effect modifier of alcohol intake on the risk of coronary heart disease (CHD)., Design: Meta-analysis of observational studies., Data Sources: Medline, citation tracking, from 1966 to 2006., Review Methods: Original studies investigating the amount of alcohol intake, combined with the frequency of alcohol consumption and/or pattern of alcohol drinking affecting the risk of CHD were extracted. Among them, cohort and case-control studies reporting sufficient data to perform statistical analyses and using people who abstained from alcohol as the reference were included., Results: Six (4 cohort and 2 case-control) out of 118 studies reviewed met the inclusion criteria. Compared with those who abstained from alcohol, regular heavy drinkers and heavy irregular or binge drinkers showed significantly different pooled relative risks of 0.75 (95% confidence interval 0.64 to 0.89) and 1.10 (1.03 to 1.17) respectively. The dose-response relation between the amount of alcohol intake and CHD risk was significantly different in regular and irregular drinkers. A J-shaped curve, with nadir around 28 grams of alcohol per week, and last protective dose of 131 grams per week, was obtained including drinkers who consumed alcohol for 2 days a week or less. Conversely, in people who consumed alcohol for more than 2 days a week a significant protective effect was seen even when drinking high amounts of alcohol., Conclusion: This meta-analysis suggests that binge and heavy irregular drinking modify the favourable effect of alcohol intake on the CHD risk. However, this conclusion should be taken with caution because of the small number of studies considered.

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.

Background: Epidemiologic studies have shown that breast cancer risk is reduced 30% to 40% in highly physically active compared with inactive women. However, the effects of moderate activities, timing of activities, and intervening effects of other risk factors remain less clear., Methods: We analyzed data on physical activity patterns in 2176 incident breast cancer cases and 2326 controls in a population-based breast cancer case-control study in Poland conducted in 2000-2003. Using unconditional logistic regression analyses, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) associated with physical activity levels (measured by average metabolic equivalents of energy expenditure hours per week), controlling for potential confounders., Results: Total adult lifetime activity reduced risk of breast cancer, with individuals in the highest quartile having an OR of 0.80 (CI = 0.67-0.96) compared with the lowest quartile. Reduced risks were most consistent for the highest quartiles of moderate-to-vigorous activities: moderate/vigorous recreational activities (OR = 0.74; CI = 0.62-0.89), outdoor activities (0.81; 0.68-0.97), heavy physical work (0.60; 0.42-0.87), and combined high intensity (metabolic equivalent >6.0) activities (0.75; 0.63-0.90). These relations were not modified by body mass index, menopausal status, or family history of breast cancer. Reductions in risk with moderate/vigorous recreational activities were stronger for larger tumors and those with nodal involvement. Women who increased their recreational activity in their 50s had significantly reduced risk, with those in the highest tertile of change being at a 27% lower risk., Conclusions: Leisure-time moderate-to-vigorous activities reduce breast cancer risk irrespective of underlying host characteristics.

Background: Smoking prevalence differs significantly across Europe. In addition, there are considerable differences in tobacco control activities across European countries. The relationship between prevalence and policy is under-researched. The present analysis examines the motivation to change smoking behaviour across 5 different European countries that differ considerably in their tobacco control activities., Methods: A population-based, representative survey of 1750 smokers, aged 16-59, from 5 different European countries (Germany, Greece, Poland, Sweden, UK) was used. Demographic variables, smoking status and the motivation to stop smoking were assessed. Motivation was assessed as, first, intending to quit (using the stages of change plus a modified stage for Precontemplation), and second, the desire to quit., Results: The majority of smokers want to stop smoking (73.5%), while only 35.0% want to stop definitely. Across countries, 10.2% definitely do not want to stop. Most of the smokers can be categorised in the Precontemplation stage (between 62.6% and 77.7% depending on the country), one of the stages of change categories. The relationship between the stages of change and the country under examination is statistically significant (chi-square = 43.466, p < 0.001). In countries with a high level of tobacco control, the proportion of people in Precontemplation is lower than in countries with low tobacco control activity., Conclusion: There are differences in the stages of change between the countries under examination. However, the categorisation of the countries into low, medium and high tobacco control activity used in this analysis does not explain these differences. Most smokers want to stop smoking, but a high proportion cannot indicate a time-frame when this is going to happen. Tobacco control efforts or other kinds of support might encourage these smokers to actually try to stop. Longitudinal studies at the population level are needed to assess, relate or monitor tobacco control activities and the intention to stop.

During the 1980's, opposing time trends were observed in coronary heart disease (CHD) rates between Eastern and Western European countries. In all former socialistic economic countries, CHD was uniformly increasing or stable, but a steady decline in CHD was observed in Western European countries. Surprisingly, during the 1990's CHD mortality substantially decreased in some Eastern European countries but not in others. These changes were accompanied by major shifts in food consumption, including the type of vegetable oils used by the population. There are two major vegetable oils consumed in Eastern Europe (rapeseed and sunflower) that differ greatly in their content of n-3 fatty acids, specifically alpha-linolenic acid (ALA). Low ALA intake has been associated with risk of fatal CHD and sudden cardiac death. The purpose of this study was to examine trends in CHD in eleven Eastern European countries to identify whether national changes in vegetable oil consumption after 1990 were associated with changes in CHD mortality rates. Our data show that countries which experienced an increase in ALA consumption also experienced a substantial decline in CHD mortality. These results were consistent in men and women. We hypothesize that the decline in CHD mortality observed in Eastern Europe can be attributed, in part, to changes in ALA consumption.

Summary: The inconsistent associations between fruit and vegetable intake and breast cancer risk may be due to heterogeneity of associations by estrogen (ER) and progesterone receptor (PR) status of the tumors. We evaluated this hypothesis in a large (2,386 cases and 2,503 controls) population-based case-control study in Poland, conducted between 2000 and 2003. We observed significant associations between reduced overall risk of breast cancer and increasing levels of total fruit intake (odds ratio (OR) for highest versus lowest quartile = 0.76, 95%CI = 0.63-0.91; p-trend = 0.01), but not for total vegetable intake (1.13 (0.93-1.37), p-trend = 0.25), after controlling for age, energy intake and known risk factors for breast cancer. The inverse association with total fruit intake was stronger for risk of ER+ (0.69 (0.54-0.88), p-trend = 0.01) than ER- tumors (0.89 (0.67-1.19), p-trend = 0.57) (p-heterogeneity = 0.02). In conclusion, this study suggests that fruit intake might have differential associations for breast tumor subtypes defined by ER status.

Background: Although a number of studies on the polymorphisms in COX1 and COX2 genes in association with risks for a number of cancers have been conducted, their relation to gastric cancer has not been well studied., Patients and Methods: Genotypes of several variants in both COX1 (Ex7+31 C>A and Ex10-4 G>A) and COX2 (-765 G>C, Ex10+837 T>C, Ex10-90 C>T, IVS5-275 T>G, and IVS7+111 T>C) were identified by TaqMan assays in 305 gastric cancer cases and 427 age- and gender-matched controls in a high-risk Polish population. Odds ratios for gastric cancer and 95% confidence intervals from unconditional logistic regression models were used to evaluate relative risks., Results: We found no statistically significant evidence that the polymorphisms tested in COX1 and COX2 are associated with gastric cancer risk., Conclusion: These results suggest that the polymorphisms examined in COX1 and COX2 do not affect the risk of gastric cancer.

Genetic variations increasing blood levels of acetaldehyde, the first metabolite of alcohol, refrain their carriers from drinking alcohol but may also put them at increased risk of cancer because of the mutagenic and carcinogenic effect of acetaldehyde. In a population-based study of 305 cases and 428 controls in Warsaw, Poland, we evaluated the effect of polymorphisms in alcohol metabolizing genes, including ADH1B (Ex9+5C>T, Ex3+23A>G, Ex3+58A>T and Ex9+77A>G), ADH1C (Ex8-56A>G and Ex6-14G>A) and ALDH2 (Ex1+82A>G), on levels of alcohol drinking and susceptibility of stomach cancer. We found that among control subjects frequency of alcohol drinking varied by alcohol metabolizing genotype. In particular, the weekly consumption of individuals carrying the AA, GA and GG genotypes of ALDH2 Ex1+82A>G polymorphism were 3.75, 2.26 and 1.53 drinks, respectively (p=0.04). However, none of the assessed polymorphisms in these 3 genes had a measurable effect on stomach cancer risk. When stratified by ALDH2 Ex1+82A>G polymorphism, alcohol-related increases in stomach cancer risk were restricted to individuals with the AG/GG genotypes, with a more than 2-fold risk among daily drinkers (OR=2.63, 95% CI=1.00-6.88) and 3-fold risk (OR=3.66, 95% CI=1.19-11.24) among those with 40 or more drink-years. In summary, our results suggested that the ALDH2 Ex1+82 G allele may be functionally deficient in eliminating acetaldehyde and discourage alcohol drinking. Furthermore, heavy drinkers of alcohol who were genetically prone to accumulate acetaldehyde may face an increased risk of stomach cancer., (Copyright (c) 2007 Wiley-Liss, Inc.)

Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (-1381C>T, -244C>T, and Ex2-659G>A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53-1.00, 0.46-0.95 and 0.39-0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies.

Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-alpha and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-alpha, ER-beta, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUAtrade mark). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women (p-trend = 0.01, both comparisons), whereas among postmenopausal women, PR levels were associated directly with BMI (p-trend = 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) = 0.86 (95% CI = 0.69-1.07) for low PR and HER2 expression vs. OR = 1.78 (95% CI = 1.25-2.55) for high expression (p-heterogeneity = 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers., ((c) 2007 Wiley-Liss, Inc.)

Aims: To give an overview of the volume of alcohol consumption, beverage preference, and patterns of drinking among adults (people 15 years and older) in central and eastern Europe (Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia) and to compare it to southern and western Europe, Russia and Ukraine., Methods: Secondary data analysis. Consumption and preferred beverage type data for the year 2002 were taken from the WHO Global Status Report on Alcohol and the WHO Global Alcohol Database., Results: Average consumption in central and eastern Europe is high with a relatively large proportion of unrecorded consumption ranging from one litre in Czech Republic and Estonia to 10.5 l in Ukraine. The proportion of heavy alcohol consumption (more than 40 g of pure alcohol per day) among men was the lowest in Bulgaria (25.8%) and the highest in Czech Republic (59.4%). Among women, the lowest proportion of heavy alcohol consumption was registered in Estonia (4.0%) and the highest in Hungary (16.0%). Patterns of drinking are detrimental with a high proportion of binge drinking, especially in the group of countries traditionally drinking vodka. In most countries, beer is now the most prevalent alcoholic beverage., Conclusions: Other studies suggest that the population drinking levels found in central and eastern Europe are linked with higher levels of detrimental health outcomes. Known effective and cost-effective programs to reduce levels of risky drinking should, therefore, be implemented, which may, in turn, lead to a reduction of alcohol-attributable burden of disease.

Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population-based case-control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one-carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73-0.96) and 0.85 (0.62-1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p-trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta-analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk.

Background: At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor., Methods: We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10,244 head and neck cancer case subjects and 15,227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided., Results: Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx., Conclusions: Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology.

We conducted a population-based case-control study of reproductive factors in Warsaw and Lódź, Poland, in 551 incident endometrial cancer cases and 1925 controls. The reproductive variable most strongly related to risk was multiparity, with subjects with three or more births having a 70% lower risk than the nulliparous women. The reduced risk was particularly strong below 55 years of age. Subjects with older ages at a first birth were also at reduced risk even after adjustment for number of births. Ages at last birth or intervals since last birth were not strongly related to risk. Spontaneous abortions were unrelated to risk, but induced abortions were associated with slight risk increases (odds ratios=1.28, 95% confidence intervals 0.8-2.1 for 3+ vs no abortions). The absence of effects on risk of later ages at, or short intervals since, a last birth fails to support the view that endometrial cancer is influenced by mechanical clearance of initiated cells. Alternative explanations for reproductive effects should be sought, including alterations in endogenous hormones.

Objective: Clarifying age-specific female breast cancer risks and interactions may provide important etiologic clues., Method: Using a population-based case-control study in Poland (2000-2003) of 2,386 incident breast cancer cases and 2,502 control subjects aged 25-74 years, we estimated age-specific breast cancer incidence rates according to risk factors., Results: Breast cancer risks were elevated among women with positive family history (FH), younger age at menarche, older age at first full-term birth, nulliparity, exogenous hormonal usage, and reduced physical activity (PA). Notwithstanding overall risks, we observed statistically significant quantitative (non-crossover) and qualitative (crossover) age interactions for all risk factors except for FH and PA. For example, nulliparity compared to parity reduced breast cancer risk among women ages 25-39 years then rates crossed or reversed, after which nulliparity increased relative risks among women ages 40-74 years., Conclusion: Though quantitative age interactions could be expected, qualitative interactions were somewhat counterintuitive. If confirmed in other populations, qualitative interactions for a continuous covariate such as age will be difficult to reconcile in a sequential (multistep or monolithic) 'stochastic' breast cancer model. Alternatively, the reversal of relative risks among younger and older women suggests subgroup heterogeneity with different etiologic mechanisms for early-onset and late-onset breast cancer types.

Background: The sex hormone-binding globulin (SHBG) is a carrier protein that modulates the bio-availability of serum sex steroid hormones, which may be involved in ovarian cancer. We evaluated whether common genetic variation in SHBG and its 3' neighbor ATP1B2, in linkage disequilibrium, is associated with the risk of epithelial ovarian cancer., Methods: The study population included 264 women with ovarian carcinoma and 625 controls participating in a population-based case-control study in Poland. Five common single nucleotide polymorphisms (SNPs) in SHGB and five in ATP1B2 were selected to capture most common variation in this region., Results: None of the SNPs evaluated was significantly associated with ovarian cancer risk, including the putative functional SNPs SHBG D356N (rs6259) and -67G>A 5'UTR (rs1799941). However, our data were consistent with a decreased ovarian cancer risk associated with the variant alleles for these two SNPs, which have been previously associated with increased circulating levels of SHBG., Conclusion: These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk.

Background: National smoking prevalence estimates are the primary basis for assessing progress in tobacco control across the world. They are based on surveys of self-reported cigarette smoking. It has been assumed that this is sufficiently accurate for policy purposes, but this assumption has not been adequately tested., Methods: We report data from the 2003 Health Survey for England, the U.S. National Health and Nutrition Examination Survey for 2001-2002, and the 2004 national smoking behaviors survey in Poland as examples of countries at different stages in the "tobacco epidemic." Self-reported cigarette and total tobacco smoking prevalence were assessed by means of the standard questions used in each country. In subsamples, specimens were collected for analysis of cotinine (saliva, N = 1,613 in England; serum, N = 4,687 in the United States; and saliva, N = 388 in Poland) providing an objective means of determining active smoking. A cut point of 15 ng/mL was used to discriminate active smoking from passive smoke exposure., Results: Self-reported cigarette smoking prevalence using the standard methods underestimated true tobacco smoking prevalence by an estimated 2.8% in England, 0.6% in the United States, and 4.4% in Poland. Cotinine concentrations in those misclassified as nonsmokers were indicative of high levels of smoke intake., Interpretation: Underestimation of smoking prevalence was minimal in the United States but significant in England and Poland. A review of methodologies for assessing tobacco smoking prevalence worldwide is urgently needed.

Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor alpha, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; P(heterogeneity) = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; P(heterogeneity) = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer.

Background and Aims: TLR4 is a cell-surface signaling receptor involved in the recognition and host response to Helicobacter pylori. The TLR4+896A>G polymorphism linked with impaired reactivity to bacterial lipopolysaccharide may play a role in gastric carcinogenesis., Methods: We assessed associations with premalignant gastric changes in 149 relatives of gastric cancer patients, including 45 with hypochlorhydria and gastric atrophy. We also genotyped 2 independent Caucasian population-based case-control studies of upper gastrointestinal tract cancer, initially in 312 noncardia gastric carcinoma cases and 419 controls and then in 184 noncardia gastric carcinomas, 123 cardia carcinomas, 159 esophageal cancers, and 211 frequency-matched controls. Odds ratios were computed from logistic models and adjusted for potential confounding factors., Results: TLR4+896G carriers had an 11-fold (95% confidence interval [CI], 2.5-48) increased odds ratio (OR) for hypochlorhydria; the polymorphism was unassociated with gastric acid output in the absence of H pylori infection. Carriers also had significantly more severe gastric atrophy and inflammation. Seventeen percent of gastric carcinoma patients in the initial study and 15% of the noncardia gastric carcinoma patients in the replication study had 1 or 2 TLR4 variant alleles vs 8% of both control populations (combined OR = 2.3; 95% CI = 1.6-3.4). In contrast, prevalence of TLR4+896G was not significantly increased in esophageal squamous cell (2%, OR = 0.2) or adenocarcinoma (9%, OR = 1.4) or gastric cardia carcinoma (11%, OR = 1.4)., Conclusions: Our data suggest that the TLR4+896A>G polymorphism is a risk factor for noncardia gastric carcinoma and its precursors. The findings underscore the role of the host innate immune response in outcome of H pylori infection.

Background: The etiology of breast cancer is not well understood and the role of occupational exposures in breast carcinogenesis is still uncertain., Methods: The population-based case-control study included 2,386 incident breast cancer cases diagnosed in 2000-2003, and 2,502 controls. Lifetime occupational histories and information on other potential breast cancer risk factors were obtained through personal interviews. Conditional logistic regression analyses calculated odds ratios (ORs) associated with various occupations and industries after control for potential confounders., Results: We found statistically significant excesses of breast cancer among engineers (OR=2.0; 95% CI: 1.0-3.8), economists (2.1; 1.1-3.8), sales occupations-retail (1.2; 1.0-1.5), and other sales occupations (1.2; 1.0-1.5). Industries showing significantly elevated risks included special trade contractors (2.2; 1.2-4.3), electronic and electric equipment manufacturers (1.7; 1.1-2.7); and public administration/general government n.e.c. (2.7; 1.3-5.7). Each of these findings was supported by a statistically significant positive trend for duration of employment (P<0.05). A decreased breast cancer risk was observed in janitors and cleaners (0.7; 0.5-0.8)., Conclusions: In this study, we found few associations for breast cancer and occupations or industries. The suggestive findings for the electronic and electric equipment manufacturing industry and for the occupations with potential exposure to magnetic fields deserve further evaluation.

Folate deficiency has been implicated in the etiology of stomach cancer through abnormal DNA methylation and disrupted DNA synthesis and repair. Enzyme-coding genes involved in folate metabolism are often polymorphic. In a population-based study of 305 cases and 427 controls in Warsaw, Poland, we evaluated the risk of stomach cancer in relation to polymorphisms in folate-metabolizing genes, including MTHFR (Ex5+79C>T and Ex8-62A>C), MTR (Ex26-20A>G), and MTRR (Ex2-64A>G, Ex5+123C>T, Ex15+572C>T, Ex15-405A>T, Ex9-85C>T, Ex15-526G>A, and Ex14+14C>T). Polymorphisms in the MTHFR gene were not associated with stomach cancer risk. No notable effect was found for polymorphisms in MTR or MTRR either, although MTR Ex26-20 A>G and MTRR Ex5+123C>T polymorphisms were associated with a borderline increased risk of stomach cancer (MTR Ex26-20A>G, AG/GG versus AA: odds ratio, 1.35; 95% confidence interval, 0.96-1.90; MTRR Ex5+123C>T, CT/TT versus CC: odds ratio, 1.30; 95% confidence interval, 0.93-1.82). We did not find significant interactions between polymorphisms in MTHFR, MTR, and MTRR genes and dietary folate and alcohol consumption. Our study did not identify strong genetic determinants in the folate metabolism pathway for stomach cancer risk.

Helicobacter pylori infection, the dominant risk factor for gastric cancers, has been shown to elicit T helper type 1 (Th1) polarized immunological responses. We conducted a population-based study of 305 gastric cancer cases and 427 age- and gender-matched controls in Warsaw, Poland, to evaluate the association with several variants in genes responsible for Th1-cell-mediated response. Genotyping was performed on genomic DNA by TaqMan(TM) assays to determine TNFA (-308 G>A, -417 G>A, -555 G>A, -1036 C>T, -1042 C>A, -1210 T>C), IL1A (-889 C>T), IFNGR2 (Ex7-128 T>C, Ex2-34 C>G and Ex2-16 A>G) and IL12A (IVS2-798 T>A, IVS2-701 C>A and Ex7+277 G>A) polymorphisms. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for sex, age, education and smoking status. Out of six single nucleotide polymorphisms (SNPs) tested in TNFA, gastric cancer risk was significantly associated with the TNFA (-308 G>A) polymorphism, with ORs of 1.4 (95% CI: 1.0-2.0) for the G/A and 2.5 (95% CI: 1.3-4.9) for the A/A genotype carriers, when compared with the more frequent genotype (G/G) (P-trend < 0.001). Among the three tested SNPs in the IFNGR2 gene, only the Ex7-128C>T polymorphism was associated with increased risk, with ORs of 1.5 (95% CI: 1.0-2.3) for T/C and 1.7 (95% CI: 1.1-2.7) for C/C carriers when compared with T/T carriers (P-trend = 0.01). Subjects carrying both IFNGR2 Ex7-128 C/C and TNFA -308 A/A genotypes had the highest risk (OR = 5.5, 95% CI: 1.5-19.4), although the interaction was not statistically significant. IL1A (-889 C>T) and the three examined IL12A variants were unrelated to gastric cancer risk. Our findings suggest that two Th1-related polymorphisms (TNFA -308 A>G and IFNGR2 Ex7-128 C>T) may increase the risk of gastric cancer.