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Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Sante study.

ABSTRACT: BACKGROUND:High consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in "human-like" mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown. METHODS:We used world global data to demonstrate that colorectal cancer incidence and mortality are associated with increased national meat consumption. In a well-defined large cohort, we used glycomics to measure daily Neu5Gc intake from red meat and dairy, and investigated serum as well as affinity-purified anti-Neu5Gc antibodies. Based on 24-h dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ??18?years of the NutriNet-Santé study. Serum and affinity-purified anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24-h dietary records (aged 45-60, Q1-Q4; aged >?60, Q1 and Q4; 10 men/women per quartile). RESULTS:We found that high-Neu5Gc diet, gender, and age affect the specificity, levels, and repertoires of anti-Neu5Gc IgG immune responses, but not their affinity. Men consumed more Neu5Gc than women, mostly from red meat (p?=?0.0015), and exhibited higher overall serum anti-Neu5Gc IgG levels by ELISA (3.94?ng/?l versus 2.22?ng/?l, respectively; p?=?0.039). Detailed glycan microarray analysis against 56 different glycans revealed high Neu5Gc-specificity with increased anti-Neu5Gc IgG and altered repertoires, associated with higher consumption of Neu5Gc from red meat and cow dairy. Affinity purification of serum anti-Neu5Gc antibodies revealed increased levels and biased array repertoire patterns, without an increase in antibody affinity, in individuals consuming higher Neu5Gc levels. Furthermore, in a high-meat diet, antibody diversity patterns on glycan microarrays shifted towards Neu5Gc?3-linked glycans, increasing the ?3/?6-glycans ratio score. CONCLUSIONS:We found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc intake from red meat and dairy. These precise rational methodologies allowed to develop a Gcemic index to simplify the assessment of Neu5Gc in foods that could potentially be adapted for dietary recommendations to reduce cancer risk.

SUBMITTER: Bashir S

PROVIDER: S-EPMC7510162 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study.

Bashir Salam S Fezeu Leopold K LK Leviatan Ben-Arye Shani S Yehuda Sharon S Reuven Eliran Moshe EM Szabo de Edelenyi Fabien F Fellah-Hebia Imen I Le Tourneau Thierry T Imbert-Marcille Berthe Marie BM Drouet Emmanuel B EB Touvier Mathilde M Roussel Jean-Christian JC Yu Hai H Chen Xi X Hercberg Serge S Cozzi Emanuele E Soulillou Jean-Paul JP Galan Pilar P Padler-Karavani Vered V

BMC medicine 20200923 1

<h4>Background</h4>High consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in "human-like" mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown.<h4>Methods</h4>We used world global data to demonstrate that colorectal cance ...[more]

PMID: 32962714

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Dataset Information

Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Sante study.

Publications

Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study.

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