We have located links that may give you full text access.
Genome-wide interaction analysis of folate for colorectal cancer risk.
American Journal of Clinical Nutrition 2023 August 27
BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with a decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.
OBJECTIVE: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.
METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom (3DF), and a two-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC, in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).
RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found [odds ratio: 0.93 (95% confidence intervals [CI]: 0.90-0.96), and 0.91 (0.89-0.94) per quartile higher intake, and 0.82 (0.78-0.88) for users vs. non-users, respectively]. Interactions (P-interaction <5×10-8 ) of folic acid supplement and variants in the 3p25.2 locus [in the region of Synapsin II (SYN2)/tissue inhibitor of metalloproteinase 4 (TIMP4)] were found using the traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplement was associated with decreased CRC risk among those carrying the TT genotype (OR = 0.82; 95%CI: 0.79-0.86) but increased CRC risk among those carrying the TA genotype (OR = 1.63; 95%CI: 1.29-2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8 ). No interactions were observed for dietary and total folate.
CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant -omics data are warranted to validate this finding.
OBJECTIVE: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.
METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom (3DF), and a two-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC, in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).
RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found [odds ratio: 0.93 (95% confidence intervals [CI]: 0.90-0.96), and 0.91 (0.89-0.94) per quartile higher intake, and 0.82 (0.78-0.88) for users vs. non-users, respectively]. Interactions (P-interaction <5×10-8 ) of folic acid supplement and variants in the 3p25.2 locus [in the region of Synapsin II (SYN2)/tissue inhibitor of metalloproteinase 4 (TIMP4)] were found using the traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplement was associated with decreased CRC risk among those carrying the TT genotype (OR = 0.82; 95%CI: 0.79-0.86) but increased CRC risk among those carrying the TA genotype (OR = 1.63; 95%CI: 1.29-2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8 ). No interactions were observed for dietary and total folate.
CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant -omics data are warranted to validate this finding.
Full text links
Related Resources
Trending Papers
Renin-Angiotensin-Aldosterone System: From History to Practice of a Secular Topic.International Journal of Molecular Sciences 2024 April 5
Albumin: a comprehensive review and practical guideline for clinical use.European Journal of Clinical Pharmacology 2024 April 13
Revascularization Strategy in Myocardial Infarction with Multivessel Disease.Journal of Clinical Medicine 2024 March 27
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Interstitial Lung Disease: A Review.JAMA 2024 April 23
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app