Coffee consumption and cancer risk: a Mendelian randomisation study

BackgroundCoffee contains many bioactive chemicals and associations with cancer have been reported in observational studies. In this Mendelian randomisation (MR) study we investigated the causal associations of coffee consumption with a broad range of cancers.Materials and methodsTwelve independent genetic variants proxied coffee consumption. Genetically-predicted risk of any cancer (59,647 cases) and 22 site-specific cancers was estimated in European-descent individuals in UK Biobank. Univariable and multivariable MR analyses were conducted.ResultsGenetically-predicted coffee consumption was not associated with risk of any cancer in the main analysis (OR 1.05, 95% CI 0.98–1.14, p = 0.183) but was associated with an increased risk of digestive system cancer (OR 1.28, 95% CI 1.09–1.51, p = 0.003), driven by a strong association with oesophageal cancer (OR 2.79, 95% CI 1.73–4.50, p = 2.5×10^?5). This association was consistent after adjustment for genetically-predicted body mass index, smoking and alcohol consumption. There was no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied. However, genetically-predicted coffee consumption was associated with increased risk of multiple myeloma (OR 2.25, 95% CI 1.30–3.89, p = 0.004) and reduced ovarian cancer risk (OR 0.63, 95% CI 0.43–0.93, p = 0.020).ConclusionsThis MR study provides strong support for a causal association of coffee consumption with oesophageal cancer, but not for the majority of cancer types, and the underlying mechanisms require investigation.     

A Bayesian approach to Mendelian randomisation with dependent instruments

Mendelian randomisation (MR) is a method for establishing causality between a risk factor and an outcome by using genetic variants as instrumental variables. In practice, the association between individual genetic variants and the risk factor is often weak, which may lead to a lack of precision in the MR and even biased MR estimates. Usually, the most significant variant within a genetic region is selected to represent the association with the risk factor, but there is no guarantee that this variant will be causal or that it will capture all of the genetic association within the region. It may be advantageous to use extra variants selected from the same region in the MR. The problem is to decide which variants to select. Rather than selecting a specific set of variants, we investigate the use of Bayesian model averaging (BMA) to average the MR over all possible combinations of genetic variants. Our simulations demonstrate that the BMA version of MR outperforms classical estimation with many dependent variants and performs much better than an MR based on variants selected by penalised regression. In further simulations, we investigate robustness to violations in the model assumptions and demonstrate sensitivity to the inclusion of invalid instruments. The method is illustrated by applying it to an MR of the effect of body mass index on blood pressure using SNPs in the FTO gene.     

Genetically predicted body composition in relation to cardiometabolic traits: a Mendelian randomization study

European Journal of Epidemiology - Fat mass and fat-free mass are found to be associated with different health outcomes in observational studies, but the underlying causality remains unclear. We...     

Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome

Mendelian randomisation (MR) estimates causal effects of modifiable phenotypes on an outcome by using genetic variants as instrumental variables, but its validity relies on the assumption of no pleiotropy, that is, genes influence the outcome only through the given phenotype. Excluding pleiotropy is difficult, but the use of multiple instruments can indirectly address the issue: if all genes represent valid instruments, their MR estimates should vary only by chance. The Sargan test detects pleiotropy when individual phenotype, outcome and genotype data are measured in the same subjects. We propose an alternative approach to be used when only summary genetic data are available or data on gene‐phenotype and gene‐outcome come from different subjects. The presence of pleiotropy is investigated using the between‐instrument heterogeneity Q test (together with the I² index) in a meta‐analysis of MR Wald estimates, derived separately from each instrument. For a continuous outcome, we evaluate the approach through simulations and illustrate it using published data. For the scenario where all data come from the same subjects, we compare it with the Sargan test. The Q test tends to be conservative in small samples. Its power increases with the degree of pleiotropy and the sample size, as does the precision of the I² index, in which case results are similar to those of the Sargan test. In MR studies with large sample sizes based on summary data, the between‐instrument Q test represents a useful tool to explore the presence of heterogeneity due to pleiotropy or other causes. Copyright © 2015 John Wiley & Sons, Ltd.     

Water constituents and trace elements in relation to cardiovascular diseases

Significant inverse correlations between the hardness of drinking water and local cardiovascular mortality rates are found consistently in major national studies and less consistently within smaller regions. A number of bulk and trace constituents of finished water at the treatment plant show correlations with mortality of equal but not greater magnitude to the correlations of hardness with mortality. Little is known about these relationships with tap water, but levels of several trace metals of biological significance are known to vary markedly within water distribution systems and are probably related to types of pipe and the corrosiveness of the water supplied. Tap water studies and studies of localities within smaller regions are recommended to disentangle the association of water quality and health from the associations of both to other regionally distributed factors. Rainfall is one such factor which may influence the content of both drinking water and soil and thus human mineral intake. A number of other environmental and social factors seem unlikely to be intermediaries from the results of several multivariate studies.     

同型半胱氨酸与心脑血管疾病高危因素的孟德尔随机化研究

目的 采用孟德尔随机化方法,探讨同型半胱氨酸(Hcy)含量与心脑血管疾病高危因素间的潜在因果关联.方法 基于常州市武进区自然人群队列的2611个研究样本,采用全基因组芯片进行基因分型,选取全基因组关联研究确定的18个Hcy含量相关的单核苷酸多态性位点(Single Nucleotide Polymorphisms,SNPs)作为工具变量,构建Hcy的加权遗传评分(wGRS),分析Hcy相关wGRS与血压、空腹血糖、血脂等高危因素的关系.结果 孟德尔随机化研究结果显示,未发现Hcy相关wGRS与血压、血脂存在显著关联.在不饮酒者中,wGRS与血糖水平表现为正性统计学关联(β=0.33,95％ CI:0.03～0.63,P＜0.05);在饮酒者中,wGRS与血糖水平表现为负性统计学关联(β=-0.28,95％CI:-0.55～0.00,P＜0.05).结论 Hcy相关wGRS与血压、血脂无统计学关联,但对血糖的影响在不同饮酒状态者中的效应存在差别.     

Challenges for research and prevention in relation to work and cardiovascular diseases

The purpose of this paper is to discuss future challenges for research and prevention in the field of work environment and cardiovascular diseases (CVD). First, research on CVD and work during the last half of the 20th century is discussed. Second, the theories dominating the last 20 years are presented. Third, cardiovascular and occupational epidemiology are compared, and it is stressed that occupational epidemiology should avoid the individualistic bias of mainstream cardiovascular epidemiology. Finally, future challenges are discussed, and improvements are recommended concerning the use of intermediate end points, intervention research, theories about chemical and physical risk factors, the use of a unifying model for society, stress, and health, and the application of integrated prevention. It is concluded that research on CVD and work can play an important part in the development of integrated prevention strategies for the next century.     

Prevalence of cardiovascular diseases in Punjab,Pakistan: a cross-sectional study

Aim

The purpose of the present study was to measure the frequency of CVDs and some of the risk factors and to familiarize people with information on the high rates of mortality and morbidity due to CVDs in the studied areas of Punjab, Pakistan.

Subjects

Cardiovascular diseases (CVDs) are the leading cause of sudden death. CVDs are a major health problem in Pakistan, and the number of patients is increasing daily.

Aim

The purpose of the present study was to measure the frequency of CVDs and some of the risk factors and to familiarize people with information on the high rates of mortality and morbidity due to CVDs in the studied areas of Punjab, Pakistan.

Method

A cross-sectional study was conducted to investigate the prevalence of cardiovascular diseases in the local population of 53 cities in Punjab, Pakistan. A total of 6351 individuals were contacted to collect data using a questionnaire from October 2014 to September 2015. Data were collected directly by meeting the participants or indirectly through relatives and friends.

Results

Of the participants, 49.2% (3127/6351) were male and 50.8% (3224/6351) female. The data showed that 17.5% (1109/6351) of the population had CVDs with 16.6% (519/3127) being male and 18.3% (590/3224) female.

Conclusion

This study concluded that CVDs are a serious problem for both genders and affected 17.5% of the studied population. Diseases are more common in females than males with young age of onset. An inactive lifestyle, low level of activity and family history of disease could be disease risk factors in the study area.

     

饮茶与恶性肿瘤发病风险关联的孟德尔随机化研究

目的采用孟德尔随机化(MR)方法探讨饮茶与恶性肿瘤发病之间的关联。方法利用中国慢性病前瞻性研究中100 639名具有全基因组基因分型数据的研究对象, 剔除基线时患有恶性肿瘤的个体, 最终纳入分析100 218名。饮茶信息为基线自报, 按是否每日饮茶、每日饮茶杯数、每日饮茶克数分别进行分析。采用二阶段最小二乘回归模型计算3个饮茶变量与随访期间新发的全部恶性肿瘤及多种类型恶性肿瘤(胃癌、肝和肝内胆管癌、结肠直肠癌、气管/支气管和肺癌以及女性乳腺癌)的关联。为控制饮酒行为的影响, 进一步采用多变量MR法或限制在不饮酒人群中进行分析。利用逆方差加权、加权中位数法、MR-Egger法等进行敏感性分析。结果分别使用54、42、28个SNP位点构建非加权遗传风险评分作为上述3个饮茶变量的工具变量。研究对象随访(11.4±3.0)年, 期间确定新发的恶性肿瘤6 886名。模型中调整年龄、年龄2、性别、地区、芯片类型及12个遗传主成分后, MR分析的结果显示, 饮茶与全部恶性肿瘤以及各种类型的恶性肿瘤的发病无统计学关联。相比于非每日饮茶者, 每日饮茶者的全部恶性肿瘤及部分亚型(胃癌、肝和肝内胆管癌、结肠...     

Disability due to cardiovascular diseases

Extension of the time limits of temporary disability (TD) is an important method in preventing the disablement due to the key cardiac-and-vascular pathologies. Thus, the extension of TD term for patients with favorable clinical and labor prognostications and realization, during the same time period, of active all-possible therapeutic-and-recovery measures enabled a majority of such patients to catch up with their ability to work and to resume their former occupations.