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Assessment of moderate coffee consumption and risk of epithelial ovarian cancer: a Mendelian randomization study.

ABSTRACT: Background:Coffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal. Methods:We used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44?062 individuals of European ancestry from the Ovarian Cancer Association Consortium (OCAC), and combined instrumental variable estimates using a Wald-type ratio estimator. Results:For all EOC cases, the causal odds ratio (COR) for genetically predicted consumption of one additional cup of coffee per day was 0.92 [95% confidence interval (CI): 0.79, 1.06]. The COR was 0.90 (95% CI: 0.73, 1.10) for high-grade serous EOC. The COR for genetically predicted consumption of an additional 80?mg caffeine was 1.01 (95% CI: 0.92, 1.11) for all EOC cases and 0.90 (95% CI: 0.73, 1.10) for high-grade serous cases. Conclusions:We found no evidence indicative of a strong association between EOC risk and genetically predicted coffee or caffeine levels. However, our estimates were not statistically inconsistent with earlier observational studies and we were unable to rule out small protective associations.

SUBMITTER: Ong JS

PROVIDER: S-EPMC6186013 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Assessment of moderate coffee consumption and risk of epithelial ovarian cancer: a Mendelian randomization study.

Ong Jue-Sheng JS Hwang Liang-Dar LD Cuellar-Partida Gabriel G Martin Nicholas G NG Chenevix-Trench Georgia G Quinn Michael C J MCJ Cornelis Marilyn C MC Gharahkhani Puya P Webb Penelope M PM MacGregor Stuart S

International journal of epidemiology 20180401 2

<h4>Background</h4>Coffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal.<h4>Methods</h4>We used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44 062 indi ...[more]

PMID: 29186515

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Project description:BackgroundThe association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association.Materials and methodsIn this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources.ResultsThe genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292).ConclusionOur MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.

Dataset Information

Assessment of moderate coffee consumption and risk of epithelial ovarian cancer: a Mendelian randomization study.

Publications

Assessment of moderate coffee consumption and risk of epithelial ovarian cancer: a Mendelian randomization study.

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