Coffee consumption and cancer risk: a Mendelian randomisation study.

BACKGROUND: Coffee 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 METHODS: Twelve 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. RESULTS: Genetically-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). CONCLUSIONS: This 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.

Selenium and cancer risk: Wide-angled Mendelian randomization analysis.

Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site-specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2 < .3) were used as instrumental variables. Genetic associations of selenium-associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P < .1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse-variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site-specific cancers or any cancer (all 22 site-specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one-unit increase in log-transformed levels: 0.83; 95% confidence interval [CI]: 0.67-1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02-1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69-1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well-powered studies.

Role of reactive oxygen intermediates in cellular responses to dietary cancer chemopreventive agents.

Epidemiological studies continue to support the premise that diets rich in fruits and vegetables may offer protection against cancer of various anatomic sites. This correlation is quite persuasive for vegetables including ALLIUM (e. g., garlic) and cruciferous (e. g., broccoli and watercress) vegetables. The bioactive food components responsible for the cancer chemopreventive effects of various edible plants have been identified. For instance, the anticancer effects of ALLIUM and cruciferous vegetables are attributed to organosulfur compounds (e. g., diallyl trisulfide) and isothiocyanates (e. g., sulforaphane and phenethyl isothiocyanate), respectively. Bioactive food components with anticancer activity are generally considered to be antioxidants due to their ability to modulate expression/activity of antioxidative and phase 2 drug-metabolizing enzymes and scavenging free radicals. At the same time, more recent studies have provided convincing evidence to indicate that certain dietary cancer chemopreventive agents cause generation of reactive oxygen species (ROS) to trigger signal transduction culminating in cell cycle arrest and/or programmed cell death (apoptosis). Interestingly, the ROS generation by some dietary anticancer agents is tumor cell specific and does not occur in normal cells. This review summarizes experimental evidence supporting the involvement of ROS in cellular responses to cancer chemopreventive agents derived from common edible plants.