Dataset Information

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

ABSTRACT:

Background

The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.

Objectives

To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).

Methods

Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.

Results

Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.

Conclusions

These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

SUBMITTER: Tsilidis KK

PROVIDER: S-EPMC8168352 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Tsilidis Konstantinos K KK Papadimitriou Nikos N Dimou Niki N Gill Dipender D Lewis Sarah J SJ Martin Richard M RM Murphy Neil N Markozannes Georgios G Zuber Verena V Cross Amanda J AJ Burrows Kimberley K Lopez David S DS Key Timothy J TJ Travis Ruth C RC Perez-Cornago Aurora A Hunter David J DJ van Duijnhoven Fränzel J B FJB Albanes Demetrius D Arndt Volker V Berndt Sonja I SI Bézieau Stéphane S Bishop D Timothy DT Boehm Juergen J Brenner Hermann H Burnett-Hartman Andrea A Campbell Peter T PT Casey Graham G Castellví-Bel Sergi S Chan Andrew T AT Chang-Claude Jenny J de la Chapelle Albert A Figueiredo Jane C JC Gallinger Steven J SJ Giles Graham G GG Goodman Phyllis J PJ Gsur Andrea A Hampe Jochen J Hampel Heather H Hoffmeister Michael M Jenkins Mark A MA Keku Temitope O TO Kweon Sun-Seog SS Larsson Susanna C SC Le Marchand Loic L Li Christopher I CI Li Li L Lindblom Annika A Martín Vicente V Milne Roger L RL Moreno Victor V Nan Hongmei H Nassir Rami R Newcomb Polly A PA Offit Kenneth K Pharoah Paul D P PDP Platz Elizabeth A EA Potter John D JD Qi Lihong L Rennert Gad G Sakoda Lori C LC Schafmayer Clemens C Slattery Martha L ML Snetselaar Linda L Schenk Jeanette J Thibodeau Stephen N SN Ulrich Cornelia M CM Van Guelpen Bethany B Harlid Sophia S Visvanathan Kala K Vodickova Ludmila L Wang Hansong H White Emily E Wolk Alicja A Woods Michael O MO Wu Anna H AH Zheng Wei W Bueno-de-Mesquita Bas B Boutron-Ruault Marie-Christine MC Hughes David J DJ Jakszyn Paula P Kühn Tilman T Palli Domenico D Riboli Elio E Giovannucci Edward L EL Banbury Barbara L BL Gruber Stephen B SB Peters Ulrike U Gunter Marc J MJ

The American journal of clinical nutrition 20210601 6

<h4>Background</h4>The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.<h4>Objectives</h4>To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-ca ...[more]

PMID: 33740060

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Project description:ObjectivesPrevious observational studies have suggested associations between concentrations of several circulating micronutrients and sarcopenia. However, the causality inferred from those studies was subjected to residual confounding and reverse causation. Therefore, we aimed to examine the causal effects of the levels of genetically predicted serum micronutrients on sarcopenia.MethodsSingle nucleotide polymorphisms (SNPs) were chosen from large-scale genome-wide association studies of participants only with European descent and were used as genetic instruments for the levels of 10 serum micronutrients (calcium, magnesium, selenium, copper, iron, zinc, Vitamin A, Vitamin B12, Vitamin D, and Vitamin E). Sarcopenia was defined by referencing to the 2019 definition given by the European Working Group on Sarcopenia in Older People (EWGSOP). A two-sample Mendelian randomization (MR) analysis was carried out to examine the associations between the levels of genetically predicted serum micronutrients and the risk of sarcopenia. Then, sensitivity analyses (including weighted median, MR-Egger and leave-one-out sensitivity analyses) were performed to evaluate the robustness of study findings. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs) per one standard deviation (SD) increase in the exposures.ResultsA total of 378,635 UK Biobank participants, including 572 participants who were identified with sarcopenia, were included in this study. The iron status was shown to have a clear effect on the risk of sarcopenia based on MR analyses. The per one SD increment in the genetically-determined serum iron level corresponded to a 53% increase in the risk of sarcopenia (OR = 1.53, 95% CI: 1.31-1.78, P = 0.001). The exclusion of SNPs of the circulating iron level (i.e., rs1799945 SNP, rs1800562 SNP or rs855791 SNP) did not attenuate the magnitude of the signal in MR analysis. There was little evidence supporting the associations between other remaining micronutrients and sarcopenia.ConclusionsAn increased risk of sarcopenia was observed with a genetically higher concentration of iron, suggesting that iron may play a role in the occurrence or development of sarcopenia.

Project description:BackgroundObservational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors.MethodsWe applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively.ResultsIn the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 × 10-10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31-0.62, p = 9.91 × 10-8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88 × 10-8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 × 10-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk.ConclusionsBMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.

Dataset Information

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Background

Objectives

Methods

Results

Conclusions

Publications

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

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