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

Tsilidis, Konstantinos K.; Papadimitriou, Nikos; Dimou, Niki; Lewis, Sarah J.; Martin, Richard M.; Murphy, Neil; Zuber, Verena; Cross, Amanda J.; Burrows, Kimberley; López, David S.; Key, Timothy J.; Travis, Ruth C.; Pérez-Cornago, Aurora; Hunter, David J.; Duijnhoven, Fränzel J.B. van; Albanês, Demetrius; Arndt, Volker; Berndt, Sonja I.; Bézieau, Stéphane; Bishop, D. Timothy; Boehm, Juergen; Brenner, Hermann; Burnett‐Hartman, Andrea N.; Campbell, Peter T.; Casey, Graham; Castellví–Bel, Sergi; Chan, Andrew T.; Chang‐Claude, Jenny; Chapelle, Albert de la; Figueiredo, Jane C.; Gallinger, Steven; Giles, Graham G.; Goodman, Phyllis J.; Gsur, Andrea; Hampe, Jochen; Hampel, Heather; Hoffmeister, Michael; Jenkins, Mark A.; Keku, Temitope O.; Kweon, Sun‐Seog; Larsson, Susanna C.; Marchand, Loı̈c Le; Li, Christopher I.; Li, Li; Lindblom, Annika; Martín, Vicente; Milne, Roger L.; Nan, Hongmei; Nassir, Rami; Newcomb, Polly A.; Offit, Kenneth; Pharoah, Paul D.P.; Platz, Elizabeth A.; Potter, John D.; Qi, Lihong; Rennert, Gad; Sakoda, Lori C.; Schafmayer, Clemens; Slattery, Martha L.; Snetselaar, Linda; Schenk, Jeanette M.; Thibodeau, Stephen N.; Ulrich, Cornelia M.; Guelpen, Bethany Van; Harlid, Sophia; Visvanathan, Kala; Vodičková, Ľudmila; Wang, Hansong; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Wang, Zheng; Bueno‐de‐Mesquita, Bas; Boutron‐Ruault, Marie‐Christine; Hughes, David J.; Jakszyn, Paula; Kühn, Tilman; Palli, Domenico; Riboli, Elio; Giovannucci, Edward; Banbury, Barbara L.; Gruber, Stephen B.; Peters, Ulrike; Gunter, Marc J.

doi:10.1093/ajcn/nqab003

Cited by 36 publications

(10 citation statements)

References 61 publications

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“…Therefore, CORSA represents an active and leading player in cooperation, support actions, and consortia. So far, CORSA contributed to multiple international consortia such as Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ], COlorectal cancer GENeTics (COGENT) and COnsortium of METabolomics Studies (COMETS) [ 13 ]. Furthermore, CORSA was a partner in two ERANET-TRANSCAN-funded projects: MetaboCCC [ 11 , 12 , 44 , 45 , 46 , 50 , 51 ], and “Biomarkers related to folate-dependent metabolism in colorectal cancer recurrence and survival” (FOCUS) [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Colorectal Cancer Study of Austria (CORSA): A Population-Based Multicenter Study

Gsur

Baierl

Brezina

2021

Biology

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The COloRectal cancer Study of Austria (CORSA) is comprised more than 13,500 newly diagnosed colorectal cancer (CRC) patients, patients with high- and low-risk adenomas as well as population-based controls. The recruitment for the CORSA biobank is performed in close cooperation with the invited two-stage CRC screening project “Burgenland PREvention trial of colorectal Disease with ImmunologiCal Testing” (B-PREDICT). Annually, more than 150,000 inhabitants of the Austrian federal state Burgenland aged between 40 and 80 are invited to participate using FIT-tests as an initial screening. FIT-positive tested participants are offered a diagnostic colonoscopy and are asked to take part in CORSA, sign a written informed consent, complete questionnaires concerning dietary and lifestyle habits and provide an ethylenediaminetetraacetic acid (EDTA) blood sample as well as a stool sample. Additional CRC cases have been recruited at four hospitals in Vienna and a hospital in lower Austria. A major strength of CORSA is the population-based controls who are FIT-positive and colonoscopy-confirmed to be free of polyps and/or CRC.

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Section: Discussionmentioning

confidence: 99%

Colorectal Cancer Study of Austria (CORSA): A Population-Based Multicenter Study

Gsur

Baierl

Brezina

2021

Biology

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“…Although MTHFR 677C → T polymorphism has been linked to an inverse association with CRC (RR = 0.62; 95% CI 0.44, 0.90) (Lee et al., 2012 ), several recent large mendelian randomisation studies have revealed no association between MTHFR polymorphism and breast cancer or CRC risk, emphasising the need for more research (Papadimitriou et al., 2021 ; Tsilidis et al., 2021 ; Yuan et al., 2021 ).…”

Section: Assessmentmentioning

confidence: 99%

Scientific opinion on the tolerable upper intake level for folate

Turck,

Bohn,

Castenmiller

et al. 2023

EFS2

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Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose-response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1-3 years, 300 μg/day for 4-6 years, 400 μg/day for 7-10 years, 600 μg/day for 11-14 years and 800 μg/ day for 15-17 years. A UL of 200 μg/day is established for infants aged 4-11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use.It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyltetrahydrofolic acid salts. K E Y W O R D S folate, folic acid, 5-methyltetrahydrofolic acid salt, tolerable upper intake level 2 of 119 |

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“…[3][4][5][6] Given its complex absorption mechanisms and relatively low bioavailability, VB12 levels can be influenced by various factors, including pernicious anemia, vegetarians, genetic predisposition, and food-bound cobalamin malabsorption. [7][8][9][10] Furthermore, previous research has indicated that levels of VB12 can vary due to environmental factors and lifestyle choices. [11,12] However, a systematic profile of VB12 distribution in the Chinese population is limited in number, and previously published studies are relatively outdated.…”

Section: Introductionmentioning

confidence: 99%

Distribution and status of vitamin B12 in Chinese adults with hypertension: a comprehensive report across 14 provinces

Cao,

Huang,

Chen

et al. 2023

Precision Nutrition

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Background: Vitamin B12 (VB12) is an essential biomarker for population health, and its deficiency status leads to severe health burdens. A comprehensive and updated investigation on the distribution of VB12 levels and status is critically needed to address public health and clinical concerns. Methods: We conducted a cross-sectional analysis using data obtained from the Precision Medical Program, which encompassed 14 provinces in China. Specific criteria based on previously published cutoffs and our study population’s characteristics are adopted to define B12 deficiency. Biochemical B12 deficiency was identified with circulating VB12 levels <148 pmol/L. Metabolic B12 deficiency was determined with circulating VB12 levels ≥148 and ≤258 pmol/L with concomitant elevated plasma total homocysteine (tHcy ≥14 µmol/L). Normal B12 status included VB12 levels >258 pmol/L or VB12 levels ranging from 148 to 258 pmol/L with tHcy levels below 14 µmol/L. VB12 levels and status were analyzed and stratified by age, sex, and geographical region. Results: This study enrolled a total of 2174 hypertensive adults, with a mean age of 63.0 years (±13.4) and 45.8% female. The overall mean VB12 levels were 322.3 (85.0) pmol/L. The prevalence rates of B12 biochemical deficiency, metabolic deficiency, metabolic deficiency with excluded renal dysfunction, and adequate status were 0.7%, 13.3%, 11.5%, and 85.9%, respectively. Females exhibited higher VB12 levels than males, with a β value of 19.72 (95% confidence interval [CI], 10.59–28.84) in the multivariate model. The southern population demonstrated higher VB12 levels than people from the north, with a β value of −18.14 (95% CI, −25.72 to −10.76). Males had a higher prevalence of metabolic VB12 deficiency in comparison to females (15.8% vs. 10.4%). Conclusions: Our study revealed that Chinese hypertensive adults exhibit relatively higher levels of VB12. Additionally, while biochemical B12 deficiency is uncommon, a noteworthy proportion of individuals were affected by metabolic VB12 deficiency. This study has important implications for nutritional counseling and vitamin B supplement strategies.

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

Cited by 36 publications

References 61 publications

Colorectal Cancer Study of Austria (CORSA): A Population-Based Multicenter Study

Colorectal Cancer Study of Austria (CORSA): A Population-Based Multicenter Study

Scientific opinion on the tolerable upper intake level for folate

Distribution and status of vitamin B12 in Chinese adults with hypertension: a comprehensive report across 14 provinces

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