Rino Bellocco

Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis

Background:Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial.Methods:We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose–response meta-regression models and investigated potential sources of heterogeneity.Results:A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose–risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin’s and Non-Hodgkin’s lymphomas were inversely associated.Conclusions:Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.

Increased risks of circulatory diseases in late pregnancy and puerperium

We studied a nationwide Swedish cohort with 654,957 women who had 1,003,489 deliveries from 1987 through September 1995 to assess late pregnancy and puerperal risks of circulatory diseases. We used standardized incidence rate ratios to calculate relative risks [with 95% confidence intervals (CIs)]. Compared with unexposed (nonpregnant and early pregnant) women, relative risks of venous thrombosis and pulmonary embolism during the third trimester were 6.7 (95% CI = 5.7–7.8) and 2.7 (95% CI = 1.7–4.2), respectively. Around delivery (from 2 days before to 1 day after delivery), the relative risks of all assessed circulatory diseases were dramatically increased: venous thrombosis, 115.1 (95% CI = 96.4–137.0); pulmonary embolism, 80.7 (95% CI = 53.9–117.9); subarachnoid hemorrhage, 46.9 (95% CI = 19.3–98.4); intracerebral hemorrhage, 95.0 (95% CI = 42.1–194.8); cerebral infarction, 33.8 (95% CI = 10.5–84.0); and myocardial infarction, 27.0 (95% CI = 0.6–180.0). During the rest of the first 6 weeks postpartum, the risks declined but were still substantially increased for all diseases, with the exception of subarachnoid hemorrhage. The results suggest that the increased risk for circulatory diseases related to pregnancy is mainly confined to a few days around delivery.

Validity and reproducibility of self-reported total physical activity--differences by relative weight.

OBJECTIVE: Physical activity is hypothesized to reduce the risk of obesity and several other chronic diseases and enhance longevity. However, most of the questionnaires used measure only part of total physical activity, occupational and/or leisure-time activity, which might lead to misclassification of total physical activity level and to dilution of risk estimates. We evaluated the validity and reproducibility of a short self-administered physical activity questionnaire, intended to measure long-term total daily 24 h physical activity.METHOD: The questionnaire included questions on level of physical activity at work, hours per day of walking/bicycling, home/household work, leisure-time activity/inactivity and sleeping and was sent twice during one year (winter/spring and late summer). Two 7-day activity records, performed 6 months apart, were used as the reference method. One-hundred and eleven men, aged 44–78, completed the questionnaire and one or two activity records. The physical activity levels were measured as metabolic equivalents (MET)×h/day.RESULTS: Spearman correlation coefficient between total daily activity score estimated from the first questionnaire and the records (validity) was 0.56 (deattenuated) and between the first and the second questionnaire (reproducibility) 0.65. Significantly higher validity correlations were observed in men with self-reported body mass index below 26 kg/m2 than in heavier men (r=0.73 vs r=0.39).CONCLUSIONS: This study indicates that the average total daily physical activity scores can be estimated satisfactorily in men using this simple self-administered questionnaire.

Mediation analysis in epidemiology: methods, interpretation and bias

In epidemiological studies it is often necessary to disentangle the pathways that link an exposure to an outcome. Typically the aim is to identify the total effect of the exposure on the outcome, the effect of the exposure that acts through a given set of mediators of interest (indirect effect) and the effect of the exposure unexplained by those same mediators (direct effect). The traditional approach to mediation analysis is based on adjusting for the mediator in standard regression models to estimate the direct effect. However, several methodological papers have shown that under a number of circumstances this traditional approach may produce flawed conclusions. Through a better understanding of the causal structure of the variables involved in the analysis, with a formal definition of direct and indirect effects in a counterfactual framework, alternative analytical methods have been introduced to improve the validity and interpretation of mediation analysis. In this paper, we review and discuss the impact of the three main sources of potential bias in the traditional approach to mediation analyses: (i) mediator-outcome confounding;(ii) exposure-mediator interaction and (iii) mediator-outcome confounding affected by the exposure. We provide examples and discuss the impact these sources have in terms of bias.

Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions

Objectives:To investigate the effects of primary HIV-1 infection (PHI) and of two antiretroviral therapies [highly active antiretroviral therapy (HAART) or reverse transcriptase inhibitors (RTI)] on activation, differentiation and survival of B cells. Methods:Naive and memory B cells from three groups [PHI (31), chronic infection (26) and healthy donors (12)] were studied for surface expression of Fas, LAIR-1, CD70, intracellular expression of Bcl-2 and spontaneous apoptosis. Fluorescence activated cell sorting (IgD+IgM+CD19+CD27+) and short-term cell culture to analyse induction of CD25 on B cells were performed in five patients with PHI. Patients with PHI were sampled at baseline, and after 1 and 6 months of therapy. Results were analysed by parametric and non-parametric tests and by mathematical modelling. Results:In PHI, B cells were significantly decreased; naive and memory B lymphocytes showed a high degree of activation, manifested by hypergammaglobulinaemia, altered expression of Fas and LAIR-1, and high rate of spontaneous apoptosis. Antiretroviral treatment improved the activation/differentiation status of B cells, reduced apoptosis to levels comparable to those in healthy individuals and restored the ability of B cells to respond to T cell-dependent activation. B cells showed slightly better recovery in patients taking HAART than in those taking RTI. Decreased IgM-positive memory B cells and lower induction of CD25 expression on B cells upon T cell activation at diagnosis of PHI was shown in five patients tested. These parameters normalized after 6 months of therapy. Conclusion:B cell dysfunctions found in chronic HIV-1 infection appear during PHI and initiation of antiretroviral therapy early during infection may help to preserve the B cell compartment.

Objectively Measured Physical Activity and Sedentary Time during Childhood, Adolescence and Young Adulthood: A Cohort Study

Background To know how moderate-to-vigorous physical activity (MVPA) and sedentary time change across lifespan periods is needed for designing successful lifestyle interventions. We aimed to study changes in objectively measured (accelerometry) MVPA and sedentary time from childhood to adolescence and from adolescence to young adulthood. Methods Estonian and Swedish participants from the European Youth Heart Study aged 9 and 15 years at baseline (N = 2312) were asked to participate in a second examination 6 (Sweden) to 9/10 (Estonia) years later. 1800 participants with valid accelerometer data were analyzed. Results MVPA decreased from childhood to adolescence (−1 to −2.5 min/d per year of follow-up, P = 0.01 and <0.001, for girls and boys respectively) and also from adolescence to young adulthood (−0.8 to −2.2 min/d per year, P = 0.02 and <0.001 for girls and boys, respectively). Sedentary time increased from childhood to adolescence (+15 and +20 min/d per year, for girls and boys respectively, P<0.001), with no substantial change from adolescence to young adulthood. Changes in both MVPA and sedentary time were greater in Swedish than in Estonian participants and in boys than in girls. The magnitude of the change observed in sedentary time was 3–6 time larger than the change observed in MVPA. Conclusions The decline in MVPA (overall change = 30 min/d) and increase sedentary time (overall change = 2∶45 h/d) observed from childhood to adolescence are of concern and might increase the risk of developing obesity and other chronic diseases later in life. These findings substantially contribute to understand how key health-related behaviors (physical activity and sedentary) change across important periods of life.

Loss of IL-7Ralpha is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients

Objective:Elevated levels of interleukin (IL)-7 are present in the blood of HIV-positive patients and it is known that IL-7 receptor (IL-7R)α expression decreases on T cells during HIV infection. The subset(s) of T cells with low IL-7Rα and the consequence of low IL-7Rα expression for T-cell survival are poorly characterized. Design:The frequency of IL-7Rα-negative T cells in HIV-positive patients was studied in relation to CD4 T-cell counts, IL-7 concentration and survival in culture. We analysed IL-7Rα expression in different T-cell populations and in relation to Bcl-2 expression. Methods:Specimens from 38 HIV-1 patients and 17 controls were examined. IL-7Rα and Bcl-2 expression in different T-cell populations was studied by flow cytometry. The influence of IL-7Rα expression on T-cell survival was studied by culturing T cells in the presence of IL-7. Results:Down-regulation of IL-7Rα on T cells correlated with depletion of CD4 T cells (P < 0.001) and also with increased concentration of serum IL-7 (P < 0.05). The decreased IL-7Rα expression was associated with low Bcl-2 expression and with the reduced survival capacity of T cells in the presence of IL-7 in vitro. Particularly, T cells with memory phenotype showed a decreased IL-7Rα expression in association with CD28 down-regulation. Conclusions:The positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIV-infected individuals due to IL-7Rα down-regulation. Differentiation towards a CD28-negative memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool.

Dietary Phytoestrogen, Serum Enterolactone and Risk of Prostate Cancer: The Cancer Prostate Sweden Study (Sweden)

ObjectiveBased on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer.MethodsIn our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer.ResultsHigh intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57–0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15–0.55), 0.63 (95% CI: 0.35–1.14) and 0.74 (95% CI: 0.41–1.32).ConclusionsOur results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.

Alcohol drinking and pancreatic cancer risk: a meta-analysis of the dose-risk relation

In order to provide a more precise quantification of the association between alcohol consumption and pancreatic cancer risk, we performed a meta‐analysis of relevant dose‐risk results. We conducted a PubMed search of all case‐control (N=21) and cohort (N=11) studies published up to March 2009. We computed summary relative risk (RR) estimates using either fixed‐ or, in the presence of heterogeneity, random‐effects models. The pooled RR was 0.92 (95% confidence interval, 95% CI, 0.86–0.97) for <3 drinks/day and 1.22 (95% CI, 1.12–1.34) for ≥3 drinks/day. The increased risk for heavy drinking was similar in women and men, but apparently stronger in cohort studies (RR=1.29), in studies with high quality index (RR=1.30), and did not appear to be explained by residual confounding by either history of pancreatitis or tobacco smoking. This meta‐analysis provides strong evidence for the absence of a role of moderate drinking in pancreatic carcinogenesis, coupled to an increased risk for heavy alcohol drinking. Given the moderate increase in risk and the low prevalence of heavy drinkers in most populations, alcohol appears to be responsible only for a small fraction of all pancreatic cancers.

Total physical activity in relation to age, body mass, health and other factors in a cohort of Swedish men

Background: Despite a large public health interest in physical activity and its role in obesity and other chronic diseases, only a few reports to date have addressed total levels of physical activity in relation to age, body mass, health and other lifestyle factors.Objective: To investigate whether levels of total physical activity among men are associated with age, body mass, self-rated health and other lifestyle factors in a cross-sectional setting.Methods: In a population-based cohort of 33 466 men aged 45–79 y in central Sweden, we collected information about physical activity through a self-administered questionnaire. Level of total physical activity was assessed quantitatively based on six questions on different activities: work/occupation, housework, walking/bicycling, exercise, inactive leisure time and sleeping. The physical activity levels were measured as metabolic equivalents, MET-h/day. The relation between age, body mass index, smoking, education, marital status and self-rated health, and total physical activity was studied in a cross-sectional analysis, using multivariate regression.Results: Total daily physical activity was decreasing systematically between age 45 and 79 (−4.1%, 95% CI −4.6, −3.6). Obese men reported −2.6% (95% CI −3.0, −2.1) lower physical activity than normal weight men. Those with high education had −7.0% (95%CI −7.3, −6.7) lower total physical activity than those with elementary school. Men with self-rated poor health had −11.3% (95%CI −12.1, −10.6) lower physical activity than those reporting very good health. The cross-sectionally observed decrease with age was greatest among obese men (−8.7%), current smokers (−7.9%), low-educated men (−5.6%) and those with poor health (−9.8%); the subgroups with very good health reported almost the same level of total physical activity (−0.6%) for age 74–79 as for age 45–49.Conclusions: The observed decreasing levels of total physical activity with age to large degree depend on health status and other factors. The characterization of subjects with low total physical activity levels is of importance for understanding observed worldwide trends in increasing prevalence of obesity. The better understanding of these phenomena might also facilitate a better planning of public health interventions with messages specifically adjusted for subgroups of population with lower physical activity.