Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing
Background - Folate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer. - Objective - We examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to som...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 2024
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| In: |
The American journal of clinical nutrition
Year: 2024, Jahrgang: 120, Heft: 3, Pages: 664-673 |
| ISSN: | 1938-3207 |
| DOI: | 10.1016/j.ajcnut.2024.07.012 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ajcnut.2024.07.012 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0002916524006099 
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| Verfasserangaben: | Elom K Aglago, Conghui Qu, Sophia Harlid, Amanda I Phipps, Robert S Steinfelder, Shuji Ogino, Claire E Thomas, Li Hsu, Amanda E Toland, Hermann Brenner, Sonja I Berndt, Daniel D Buchanan, Peter T Campbell, Yin Cao, Andrew T Chan, David A Drew, Jane C Figueiredo, Amy J French, Steven Gallinger, Peter Georgeson, Marios Giannakis, Ellen L Goode, Stephen B Gruber, Marc J Gunter, Tabitha A Harrison, Michael Hoffmeister, Wen-Yi Huang, Meredith AJ Hullar, Jeroen R Huyghe, Mark A Jenkins, Brigid M Lynch, Victor Moreno, Neil Murphy, Christina C Newton, Jonathan A Nowak, Mireia Obón-Santacana, Wei Sun, Tomotaka Ugai, Caroline Y Um, Syed H Zaidi, Konstantinos K Tsilidis, Bethany van Guelpen, Ulrike Peters |
MARC
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| 100 | 1 | |a Aglago, Elom K. |e VerfasserIn |0 (DE-588)1321850441 |0 (DE-627)1881720071 |4 aut | |
| 245 | 1 | 0 | |a Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing |c Elom K Aglago, Conghui Qu, Sophia Harlid, Amanda I Phipps, Robert S Steinfelder, Shuji Ogino, Claire E Thomas, Li Hsu, Amanda E Toland, Hermann Brenner, Sonja I Berndt, Daniel D Buchanan, Peter T Campbell, Yin Cao, Andrew T Chan, David A Drew, Jane C Figueiredo, Amy J French, Steven Gallinger, Peter Georgeson, Marios Giannakis, Ellen L Goode, Stephen B Gruber, Marc J Gunter, Tabitha A Harrison, Michael Hoffmeister, Wen-Yi Huang, Meredith AJ Hullar, Jeroen R Huyghe, Mark A Jenkins, Brigid M Lynch, Victor Moreno, Neil Murphy, Christina C Newton, Jonathan A Nowak, Mireia Obón-Santacana, Wei Sun, Tomotaka Ugai, Caroline Y Um, Syed H Zaidi, Konstantinos K Tsilidis, Bethany van Guelpen, Ulrike Peters |
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| 520 | |a Background - Folate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer. - Objective - We examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing. - Design - Participants within 2 large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of nonsilent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-β, WNT, and TP53/ATM). Multinomial logistic regression models were analyzed comparing mutated/nonmutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence interval (CI). Heterogeneity of associations of mutated compared with nonmutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and nonhypermutated tumors, because they exhibit different clinical behaviors. - Results - We included 4339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR = 0.93; 95% CI: 0.90, 0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, and ZNF521) showed nominal statistical significance (P < 0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or toward the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among nonhypermutated tumors, or according to the signaling pathways. - Conclusions - Folate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation. | ||
| 650 | 4 | |a colorectal cancer | |
| 650 | 4 | |a folate | |
| 650 | 4 | |a folic acid | |
| 650 | 4 | |a molecular subtypes | |
| 650 | 4 | |a somatic mutations | |
| 650 | 4 | |a tumor | |
| 700 | 1 | |a Qu, Conghui |e VerfasserIn |4 aut | |
| 700 | 1 | |a Harlid, Sophia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Phipps, Amanda I |e VerfasserIn |4 aut | |
| 700 | 1 | |a Steinfelder, Robert S |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ogino, Shuji |e VerfasserIn |4 aut | |
| 700 | 1 | |a Thomas, Claire E |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hsu, Li |e VerfasserIn |4 aut | |
| 700 | 1 | |a Toland, Amanda E |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brenner, Hermann |e VerfasserIn |0 (DE-588)1020516445 |0 (DE-627)691247005 |0 (DE-576)360642136 |4 aut | |
| 700 | 1 | |a Berndt, Sonja I |e VerfasserIn |4 aut | |
| 700 | 1 | |a Buchanan, Daniel D |e VerfasserIn |4 aut | |
| 700 | 1 | |a Campbell, Peter T |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cao, Yin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chan, Andrew T |e VerfasserIn |4 aut | |
| 700 | 1 | |a Drew, David A |e VerfasserIn |4 aut | |
| 700 | 1 | |a Figueiredo, Jane C |e VerfasserIn |4 aut | |
| 700 | 1 | |a French, Amy J |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gallinger, Steven |e VerfasserIn |4 aut | |
| 700 | 1 | |a Georgeson, Peter |e VerfasserIn |4 aut | |
| 700 | 1 | |a Giannakis, Marios |e VerfasserIn |4 aut | |
| 700 | 1 | |a Goode, Ellen L |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gruber, Stephen B |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gunter, Marc J |e VerfasserIn |4 aut | |
| 700 | 1 | |a Harrison, Tabitha A |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hoffmeister, Michael |d 1973- |e VerfasserIn |0 (DE-588)134103726 |0 (DE-627)560880820 |0 (DE-576)277089565 |4 aut | |
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| 700 | 1 | |a Hullar, Meredith AJ |e VerfasserIn |4 aut | |
| 700 | 1 | |a Huyghe, Jeroen R |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jenkins, Mark A |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lynch, Brigid M |e VerfasserIn |4 aut | |
| 700 | 1 | |a Moreno, Victor |e VerfasserIn |4 aut | |
| 700 | 1 | |a Murphy, Neil |e VerfasserIn |4 aut | |
| 700 | 1 | |a Newton, Christina C |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nowak, Jonathan A |e VerfasserIn |4 aut | |
| 700 | 1 | |a Obón-Santacana, Mireia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sun, Wei |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ugai, Tomotaka |e VerfasserIn |4 aut | |
| 700 | 1 | |a Um, Caroline Y |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zaidi, Syed H |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tsilidis, Konstantinos K |e VerfasserIn |4 aut | |
| 700 | 1 | |a van Guelpen, Bethany |e VerfasserIn |4 aut | |
| 700 | 1 | |a Peters, Ulrike |e VerfasserIn |4 aut | |
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