Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study

Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study

Obesity, inflammatory markers, and endometrial cancer risk: a prospective case–control study

Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03–2.41, Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu

Alcohol Consumption, Genetic Variants in Alcohol Deydrogenases, and Risk of Cardiovascular Diseases: A Prospective Study and Meta-Analysis

OBJECTIVE: First, to investigate and compare associations between alcohol consumption and variants in alcohol dehydrogenase (ADH) genes with incidence of cardiovascular diseases (CVD) in a large German cohort. Second, to quantitatively summarize available evidence of prospective studies on polymorphisms in ADH1B and ADH1C and CVD-risk. METHODS: We conducted a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort including a randomly drawn subcohort (n = 2175) and incident cases of myocardial infarction (MI; n = 230) or stroke (n = 208). Mean follow-up time was 8.2±2.2 years. The association between alcohol consumption, ADH1B or ADH1C genotypes, and CVD-risk was assessed using Cox proportional hazards regression. Additionally, we report results on associations of variants in ADH1B and ADH1C with ischemic heart disease and stroke in the context of a meta-analysis of previously published prospective studies published up to November 2011. RESULTS: Compared to individuals who drank >0 to 6 g alcohol/d, we observed a reduced risk of MI among females consuming >12 g alcohol/d (HR = 0.31; 95% CI: 0.10-0.97) and among males consuming >24 to 60 g/d (HR = 0.57; 95% CI: 0.33-0.98) or >60 g alcohol/d (HR = 0.30; 95% CI: 0.12-0.78). Stroke risk was not significantly related to alcohol consumption >6 g/d, but we observed an increased risk of stroke in men reporting no alcohol consumption. Individuals with the slow-coding ADH1B*1/1 genotype reported higher median alcohol consumption. Yet, polymorphisms in ADH1B or ADH1C were not significantly associated with risk of CVD in our data and after pooling results of eligible prospective studies [ADH1B*1/1: RR = 1.35 (95% CI: 0.98-1.88; p for heterogeneity: 0.364); ADH1C*2/2: RR = 1.07 (95% CI: 0.90-1.27; p for heterogeneity: 0.098)]. CONCLUSION: The well described association between alcohol consumption and CVD-risk is not reflected by ADH polymorphisms, which modify the rate of ethanol oxidation

Risiko und Erkrankungslast von Krebs bedingt durch Alkoholkonsum in acht europäischen Ländern basierend auf Ergebnissen der EPIC Studie

Alkoholkonsum gilt als etablierter Risikofaktor für Karzinome des oberen Verdauungstrakts, der Leber, des Dickdarms und der weiblichen Brust. Dabei ist es wahrscheinlich, dass die Stärke der Risikobeziehung zwischen Alkoholkonsum und dem Auftreten der kausal assozierten Krebsentitiäten in Abhängigkeit von den biologischen Mechanismen variiert. Jedoch fehlen bisher empirische Beweise. Europa zählt zu den Regionen mit dem höchsten Alkoholkonsum, doch existieren kaum detaillierte und ländervergleichende Informationen zur Erkrankungslast von Krebs aufgrund von Alkoholkonsum. Außerdem berücksichtigten frühere Schätzungen nicht das Risiko an Krebs zu erkranken, welches durch früheren Alkoholkonsum bedingt ist. Kürzlich wurde die Empfehlung von zwei Gläsern Alkohol pro Tag bei Männern und einem Glas pro Tag bei Frauen ausgesprochen, um alkoholbedingte Erkrankungen auf individueller und populationsbezogener Ebene zu minimieren. Es ist allerdings nicht bekannt, wie sich die Einhaltung dieser empfohlenen Obergrenze auf die Erkrankungslast von Krebs auswirken würde. Da sich die Erhöhung des Verkaufspreises von alkoholischen Getränken als effektives Mittel zur Verringerung des Alkoholkonsums auf Populationsebene erwiesen hat, erschien es weiterhin interessant, die Auswirkungen potentieller Preiserhöhungen von z.B. 25% oder 50% und deren Auswirkungen auf die Erkrankungslast von Krebs vergleichend zu untersuchen. Für die Analysen standen 109.118 Männer und 254.870 Frauen aus der European Prospective Investigation into Cancer and Nutrition (EPIC) Studie zur Verfügung, um relative Risiken in Abhängigkeit vom Alkoholkonsum in acht europäischen Ländern mittels des Competing Risk Ansatzes zu berechnen. Dabei wurde ein globales Modell für alle zur Verfügung stehenden Krebsentitäten (oberer Verdauungstrakt, Leber, Dickdarm, Mamma, Pankreas, Lunge, Magen, Blase, Niere, Prostata, Ovarien, Uterus) entwickelt, was zudem einen Test auf Unterschiede der Risikoassoziationen zuließ. Mithilfe populationsbezogener Daten zum Alkoholkonsum wurden attributable Risiken sowie der Anteil des attributablen Risikos berechnet, der auf einen Konsum über der empfohlenen Obergrenze zurückgeht. Dabei wurde der gegenwärtige Alkoholkonsum als Γ-Verteilung modelliert, welche auch für die weiteren Modellierungen der Preiserhöhungen und Einhaltung der empfohlenen Obergrenze herangezogen wurde. Während einer mittleren Nachbeobachtungszeit von 8,8 Jahren traten 6.203 Krebsfälle bei den Männern und 14.602 bei den Frauen auf. Mit jedem zusätzlich konsumierten alkoholischen Getränk erhöhte sich das Risiko an Krebs insgesamt zu erkranken, was dem erhöhten Erkrankungsrisiko an Krebs des oberen Verdauungstraktes, der Leber, des Dickdarms und der weiblichen Brust zuzuschreiben ist. Der ehemalige im Vergleich zu derzeitig leichtem Alkoholkonsum war ebenfalls mit einem deutlich erhöhten Risiko für Gesamtkrebs, Krebs des oberen Verdauungstrakts und der Leber verbunden. Bei Männern wurde ein signifikanter Unterschied in der Stärke der Assoziation für Krebs des oberen Verdauungstrakt sowie der Leber gegenüber den verbleibenden Krebsentitäten gefunden, während bei Frauen dies nur für Krebs des oberen Verdauungstrakts und die verbleibenden Krebsentitäten sichtbar war. Weiterhin konnte gezeigt werden, dass ein erheblicher Anteil der Krebsinzidenz bei Männern und Frauen auf den derzeitigen und ehemaligen Konsum von Alkohol zurückführbar ist, nämlich jeweils 45,1% und 28,1% des oberen Verdauungstrakts, 33,6% und 20,1% der Leber, 17,6% und 4,6% des Dickdarms und 5,1% der weiblichen Brust. Die hypothetische Reduktion des Alkoholkonsums auf die derzeitig empfohlenen Obergrenzen würde zu einer Verminderung der alkoholbedingten Krebsinzidenz von mehr als 40% führen. Eine Preiserhöhung von alkoholischen Getränken um 50% hätte ebenfalls einen starken Rückgang der alkoholbedingten Krebsinzidenz um mehr als 30% zur Folge. Die Ergebnisse der vorliegenden Arbeit unterstützen die derzeitige Evidenzlage zum Zusammenhang zwischen Alkoholkonsum und Krebsinzidenz. Weiterhin scheint es wahrscheinlich, dass das alkoholbedingte Erkrankungsrisiko für Krebs des oberen Verdauungstrakts und evtl. der Leber sich vom Erkrankungsrisiko für Dickdarm- oder Brustkrebs unterscheidet, was auf unterschiedliche biologische Mechanismen der Krebsentstehung durch Alkohol hinweist. Alkoholkonsum ist ein modifizierbarer Lebensstilfaktor und birgt deshalb ein großes Potential zur primären Krebsprävention. Da durch Einhaltung der empfohlenen Obergrenze des Alkoholkonsums die alkoholbedingte Krebsinzidenz beträchtlich gesenkt werden könnte, sollten hinreichend effektive Strategien zur Einhaltung der empfohlenen Obergrenze auf Bevölkerungsebene entwickelt werden. In dieser Hinsicht stellten sich leicht umzusetzende Preiserhöhungen von alkoholischen Getränken als effektives Mittel zur Senkung des Alkoholkonsums und die dadurch resultierende Erkrankungslast durch Krebs heraus. Diese Arbeit zeigt deutlich das Potential der primären Krebsprävention durch Absenkung des Alkoholkonsums und unterstreicht, dass gesundheitspolitische Maßnahmen zur Senkung des Alkoholkonsums dringend weiterverfolgt und intensiviert werden sollten.Alcohol consumption is a causal risk factor for cancers of the upper aerodigestive tract (UADT), colorectum, liver and female breast. The strength of the association is expected to differ across the alcohol-related cancers due to different carcinogenic pathways. However, empirical evidence is lacking. Although Europe is among the regions with the highest per capita alcohol consumption, detailed and comparable information on the alcohol attributable burden of cancer incidence is sparse. Former consumers of alcohol are at increased risk of cancer, but this has not been considered in prior computations of the alcohol attributable burden. In order to limit both individual and population burden of cancer due to alcohol, an upper daily limit of alcohol consumption of two drinks in men, one drink in women was recommended. However, it is unknown how adherence to the recommendation would affect the cancer burden due to alcohol consumption. Since it is known that increasing the price of alcoholic beverages is an effective tool to lower alcohol consumption on a population basis, it is valuable to estimate potential effects of price increases of e.g. 25% and 50% on the alcohol attributable burden of cancer incidence and compare these to following the current recommendations. In the present thesis, the risk of cancer due to alcohol consumption was investigated among 109,118 men and 254,870 women from eight European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Applying Cox proportional hazards regression as a competing risk approach, one global model including all single cancer endpoints (UADT, liver, colorectum, female breast, pancreas, lung, stomach, bladder, kidney, prostate, ovary, corpus uteri) was fitted, and the differences between hazard ratios were tested. Hazard ratios quantifying the risk of cancer for former compared to never consumers and for alcohol consumption as continuous function among current consumers from the EPIC study were combined with representative data on alcohol consumption. The distribution of alcohol consumption in current consumers was modelled by Γ-distribution functions. Using these functions, effects of price increases and adherence to the current recommendation on alcohol consumption were modelled. During a mean follow-up time of 8.8 years, 6,203 cancer cases in men and 14,602 cancer cases in women occured in the EPIC study. Using the competing risk approach each additional alcoholic drink increased the risk of total and alcohol-related cancer, which was driven by increased risks of cancer of the UADT, liver, colorectum and female breast. Former compared to light consumers of alcohol exhibited an increased risk of total and alcohol-related cancer, which resulted mostly from higher risks of UADT and liver cancer. Testing these hazard ratios for difference, the association of alcohol consumption with UADT and liver cancer seemed to differ from the association of alcohol consumption to other cancers in men, while in women merely associations with UADT cancer was significantly different to the association to the other cancers. An important part of the cancer incidence was found to be attributable to both former and current alcohol consumption with 45.1% and 28.1% for UADT cancer, 33.6% and 20.1% for liver cancer, 17.6% and 4.6% for colorectal cancer in men and women respectively, and 5.1% for female breast cancer. If the European populations adhered to the current recommendations of no more than two alcoholic drinks daily in men and one alcoholic drink daily in women, the overall burden of cancer incidence could be reduced by 40% or more. Increasing the retail prices of alcoholic beverages by 50% would decrease the alcohol attributable burden of cancer by at least 30%. The present results support the recent evaluation of alcohol consumption as a causal risk factor of cancer of the UADT, liver, colorectum and female breast. Furthermore, it seems likely that alcohol exhibits a greater risk on the development of UADT and liver cancer than on colorectal and breast cancer, which may be due to different carcinogenic pathways of alcohol. Since, alcohol consumption is a modifiable risk factor of cancer, it offers a great potential for primary prevention. As adherence to the recommended upper limit of alcohol consumption would substantially reduce the alcohol attributable burden of cancer, effective public health intervention targeted on heavy consumers of alcohol should be developed. With respect to public health interventions, increase of price of alcoholic beverages is a relatively easy and effective tool to lower alcohol consumption and thereby also alcohol attributable burden of cancer. This work highlights the large potential of alcohol consumption for cancer prevention and underscores the current political efforts to reduce alcohol consumption in order to prevent cancer incidence

Effects of Measuring Devices and Sampling Strategies on the Interpretation of Monitoring Data for Long-Term Trend Analysis

A thorough and reliable assessment of changes in sea surface water temperatures (SSWTs) is essential for understanding the effects of global warming on long-term trends in marine ecosystems and their communities. The first long-term temperature measurements were established almost a century ago, especially in coastal areas, and some of them are still in operation. However, while in earlier times these measurements were done by hand every day, current environmental long-term observation stations (ELTOS) are often fully automated and integrated in cabled underwater observatories (UWOs). With this new technology, year-round measurements became feasible even in remote or difficult to access areas, such as coastal areas of the Arctic Ocean in winter, where measurements were almost impossible just a decade ago. In this context, there is a question over what extent the sampling frequency and accuracy influence results in long-term monitoring approaches. In this paper, we address this with a combination of lab experiments on sensor accuracy and precision and a simulated sampling program with different sampling frequencies based on a continuous water temperature dataset from Svalbard, Arctic, from 2012 to 2017. Our laboratory experiments showed that temperature measurements with 12 different temperature sensor types at different price ranges all provided measurements accurate enough to resolve temperature changes over years on a level discussed in the literature when addressing climate change effects in coastal waters. However, the experiments also revealed that some sensors are more suitable for measuring absolute temperature changes over time, while others are more suitable for determining relative temperature changes. Our simulated sampling program in Svalbard coastal waters over 5 years revealed that the selection of a proper sampling frequency is most relevant for discriminating significant long-term temperature changes from random daily, seasonal, or interannual fluctuations. While hourly and daily sampling could deliver reliable, stable, and comparable results concerning temperature increases over time, weekly sampling was less able to reliably detect overall significant trends. With even lower sampling frequencies (monthly sampling), no significant temperature trend over time could be detected. Although the results were obtained for a specific site, they are transferable to other aquatic research questions and non-polar regions

Baseline characteristics across categories of baseline alcohol consumption in 815 men of a randomly drawn subcohort.

<p>Baseline characteristics across categories of baseline alcohol consumption in 815 men of a randomly drawn subcohort.</p

Baseline characteristics across drinking categories in 1360 women of a randomly drawn subcohort.

<p>Baseline characteristics across drinking categories in 1360 women of a randomly drawn subcohort.</p

Relative Risks and 95% CI from a meta-analysis of rs698 or rs1693482 in the <i>ADH1C</i> gene and CVD.

<p>Estimates are for the comparison of the slow-coding genotype (<i>ADH1C*2/2</i>) with the fast-coding genotype (<i>ADH1C*1/1</i>) (A) Including risk estimates not adjusted for alcohol consumption. (B) Including risk estimates adjusted for alcohol consumption. Data for the Second Northwick Park Heart Study obtained by personal communication with the corresponding author.</p

Relative Risks of MI and stroke across categories of baseline alcohol consumption in women.

<p>Model 1 stratified by age at recruitment and adjusted for BMI, waist circumference, smoking status, educational attainment, physical activity, non-alcohol energy intake, prevalent hypertension, prevalent diabetes mellitus, and plasma total cholesterol level.</p><p>Model 2: Model 1 plus past alcohol consumption.</p><p>Model 3: Model 1 plus <i>ADH1C</i> and <i>ADH1B</i> genotypes.</p

Relative Risks and 95% CI of CVD from a meta-analysis of rs1229984 in the <i>ADH1B</i> gene and CVD.

<p>Estimates are for the comparison of the slow-coding genotype (<i>ADH1B*1/1</i>) with the fast-coding genotype (<i>ADH1B*1/2</i> or <i>2/2</i>). (A) Including risk estimates not adjusted for alcohol consumption. (B) Including risk estimates adjusted for alcohol consumption.</p