Folic acid intake and folate status and colorectal cancer risk: A systematic review and meta-analysis

Moazzen, Sara; Dolatkhah, Roya; Tabrizi, Jafar Sadegh; Shaarbafi, Jabraeel; Alizadeh, Behrooz Z.; Bock, Geertruida H. de; Dastgiri, Saeed

doi:10.1016/j.clnu.2017.10.010

Cited by 78 publications

(45 citation statements)

References 52 publications

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“…In our study, colorectal cancer was the only site-specific cancer to suggest increased risk with increasing serum folate, albeit with a wide confidence interval that included a possible protective effect. A 2018 systematic review[52] reported little evidence of an effect of folic acid supplementation on colorectal cancer risk in a meta-analysis of RCTs (OR 1.07; 95%CI 0.86-1.14) with effect estimates similar in magnitude to those reported in our MR analysis. For observational studies, the WCRF-CUP meta-analysed 10 studies (6,986 cases) which examined the association between dietary folate and colorectal cancer reporting a null relationship (RR 0.99 per 200 µg/day; 95% CI 0.96-1.02)[47].…”

Section: Discussionsupporting

confidence: 73%

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

Burrows¹,

Kazmi²,

Haycock³

et al. 2019

Preprint

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Background: Epidemiological studies report evidence for an association between folate, an essential B vitamin, and the risk of several common cancers. However, both protective and harmful effects have been reported, and effects may differ by cancer site. These associations suggest that modulating dietary folate, or its synthetic form folic acid, could be used to modify population-wide cancer risk. However, observational studies are liable to biases, including residual confounding and reverse causation, thus limiting causal inference. Using Mendelian randomisation (MR), we investigated the causal relationships of genetically determined serum folate with pan-cancer risk (all cancers excluding non-melanoma skin cancers); breast, prostate, ovarian, lung, and colorectal cancers; and malignant melanoma. Methods:Using publicly available genome-wide association study (GWAS) summary data, we identified genetic instruments to proxy serum folate levels and analysed these using GWAS summary statistics of risk of pan-cancer and six site-specific cancers available from large consortia and the population-based cohort study UK Biobank (UKBB) within a two-sample Mendelian randomisation framework. We conducted MR using the inverse variance weighted (IVW) method and the likelihood-based approach. We performed sensitivity analyses to assess potential violations of MR assumptions. Results:We identified three SNPs (rs1801133, rs1999594, rs7545014) robustly associated with serum folate in a healthy, young adult Irish population using publicly available GWAS summary data. There was little evidence that genetically increased serum folate was associated with risk of pan-cancer or six site-specific cancers. Meta-analysis showed odds ratios (OR) per standard deviation (SD) increase in log10 serum folate of 0.92 (95% confidence interval 0.78-1.07) for breast cancer, 0.87 (95% confidence interval 0.71-1.06) for prostate cancer, 0.87 (95% confidence interval 0.61-1.25) for ovarian cancer, 0.87 (95% confidence interval 0.57-1.34) for lung cancer, and 1.26 (95% confidence interval 0.84-1.88) for colorectal cancer. ORs for pan-cancers and malignant melanoma in UKBB were 0.86 (95% confidence interval 0.71-1.03) and 0.57 (95% confidence interval 0.30-1.10) respectively. The results were powered to detect modest effect sizes (>80% power [α=0.05] to detect ORs 1.1 (or its inverse 0.9) for the cancer GWAS consortia) and were consistent between the two statistical approaches used (IVW and likelihood-based). Conclusions:There is little evidence that genetically increased serum folate may affect the risk of pan-cancer and six site-specific cancers. However, we may still be underpowered to detect clinically relevant but smaller magnitude effects. Our results provide some evidence that increasing levels of circulating folate through widespread supplementation or deregulation of fortification of foods with folic acid is unlikely to lead to moderate unintended population-wide increase in cancer risk.

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Section: Discussionsupporting

confidence: 73%

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

Burrows¹,

Kazmi²,

Haycock³

et al. 2019

Preprint

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“…In agreement with our results, the inverse association between dietary folate and colorectal cancer risk was observed in some case-control studies (11,12) and cohort studies (13)(14)(15) . Moreover, a 2017 meta-analysis of fourteen cohort studies and nineteen case-control studies showed that higher folate intake was associated with 29 and 23 % decreased risk of colorectal cancer risk in cohort studies and case-control studies, respectively (10) . However, no significant association was found in some epidemiological studies (16)(17)(18)(19)(20)(21)(22) .…”

Section: Discussionmentioning

confidence: 99%

“…Considering one-carbon metabolism nutrients need to be obtained from food, several epidemiological studies have assessed the association between dietary folate intake and the risk of colorectal cancer; however, the results remained inconclusive. Some (10)(11)(12)(13)(14)(15) , but not all (16)(17)(18)(19)(20)(21)(22) , epidemiological studies reported an inverse association between folate intake and colorectal cancer risk. Similarly, inverse associations between vitamin B 2 , vitamin B 6 and vitamin B 12 and colorectal risk have been observed in some studies (23)(24)(25)(26)(27) .…”

mentioning

confidence: 99%

Dietary B vitamin and methionine intakes and risk for colorectal cancer: a case–control study in China

et al. 2020

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AbstractB vitamins (including folate, vitamin B2, vitamin B6 and vitamin B12) and methionine are essential for methylation reactions, nucleotide synthesis, DNA stability and DNA repair. However, epidemiological evidence among Chinese populations is limited. The objective of this study was to evaluate B vitamins and methionine in relation to colorectal cancer risk in a Chinese population. A case–control study was conducted from July 2010 to April 2019. A total of 2502 patients with colorectal cancer were recruited along with 2538 age- (5-year interval) and sex-matched controls. Dietary data were collected using a validated FFQ. Multivariable logistic regression was used to assess OR and 95 % CI. The intake of folate, vitamin B2, vitamin B6 and vitamin B12 was inversely associated with colorectal cancer risk. The multivariable OR for the highest quartile v. the lowest quartile were 0·62 (95 % CI 0·51, 0·74; Ptrend < 0·001) for folate, 0·46 (95 % CI 0·38, 0·55; Ptrend < 0·001) for vitamin B2, 0·55 (95 % CI 0·46, 0·76; Ptrend < 0·001) for vitamin B6 and 0·72 (95 % CI 0·60, 0·86; Ptrend < 0·001) for vitamin B12. No statistically significant association was found between methionine intake and colorectal cancer risk. Stratified analysis by sex showed that the inverse associations between vitamin B12 and methionine intake and colorectal cancer risk were found only among women. This study indicated that higher intake of folate, vitamin B2, vitamin B6 and vitamin B12 was associated with decreased risk of colorectal cancer in a Chinese population.

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“…Eine weitere Metaanalyse aus kontrollierten Studien (2000-2016) zeigte, dass die absolute Folsäureaufnahme, also die zusätzliche Menge der Folsäure, die über die Ernährung zugeführt wird, sowohl in den Kohortenstudien (RR 0,71; 95 %-KI 0,59-0,86) als auch bei den Fall-Kontroll-Studien (RR 0,77; 95 %-KI 0,62-0,95) das Risiko für kolorektale Tumoren signifikant reduziert [7].…”

Section: Thieme Onkologie Aktuellunclassified

Mikronährstoffe in der Onkologie: Risiko und Nutzen – Update 2020

Mücke

Micke

Büntzel

et al. 2020

TumorDiagnostik & Therapie

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Zusammenfassung Hintergrund Das Interesse sowohl von betreuenden Ärzten als auch Tumorpatienten an der zusätzlichen Einnahme von Mikronährstoffen während einer onkologischen Therapie mit unterschiedlichen Intentionen nimmt zu. Dieses Update liefert deshalb eine Standortbestimmung zum zusätzlichen Einsatz von ausgewählten Mikronährstoffen während der Tumortherapie. Methoden Es wurde eine Literaturrecherche hinsichtlich des Einsatzes von ausgewählten Mikronährstoffen in der Onkologie, die bis 2018 in zitierfähigen Journalen erschienen sind, durchgeführt. Ergebnisse Daten zu Mikronährstoffen, die sowohl hinsichtlich der Lebensqualität als auch der Prognose einen Nutzen für onkologische Patienten bringen, als auch Erkenntnisse zu Mikronährstoffen, die für die Patienten keinen Benefit haben oder sogar schaden, werden präsentiert. Die gute Datenlage hinsichtlich Vitamin D und Selen erlaubt hier die Empfehlung zur Supplementation nach Spiegelbestimmung im Serum. Schlussfolgerung Nicht nur vorrangig onkologisch tätige Ärzte, sondern auch alle Ärzte, die Tumorpatienten mitbetreuen, sollten Kenntnisse über die wichtigsten Mikronährstoffe haben, um diese an die Patienten weiterzugeben und sie auch gezielt zum Nutzen der Patienten einzusetzen.

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Folic acid intake and folate status and colorectal cancer risk: A systematic review and meta-analysis

Cited by 78 publications

References 52 publications

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

Dietary B vitamin and methionine intakes and risk for colorectal cancer: a case–control study in China

Mikronährstoffe in der Onkologie: Risiko und Nutzen – Update 2020

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