Plasma Total Homocysteine Level in Association With Folate, Pyridoxine, and Cobalamin Status Among Iranian Primary Breast Cancer Patients

Abstract

Recently the elevated plasma total homocysteine (tHcy) concentration has been concerned as the secondary feature of tumoral proliferation and enhances the likelihood of thrombogenesis in cancer patients. The objective of this study was to determine the associations between folate, cobalamin, and pyridoxine with fasting plasma tHcy concentration in breast cancer (BC) patients. The intake levels of nutrients were assessed using a validated food frequency questionnaire in 141 newly diagnosed BC patients. The plasma tHcy and pyridoxal-5-phosphate were measured using high performance liquid chromatography with fluorescence detector. Plasma tHcy levels were observed to be significantly higher among BC participants with Stage III where the plasma concentrations of folate was also comparatively less (P < 0.05) than other stages. Dietary pyridoxine was even being consumed less at this stage (P < 0.05). The plasma, dietary, and residual variables of folate were inversely correlated with plasma tHcy concentration (P < 0.05). Dietary cobalamin was also associated negatively with tHcy (P < 0.05). The odds ratio of comparing the highest tertile of plasma cobalamin (>394 pmol/l) and folate (>11.4 ng/ml) vs. the lowest categories were associated with reduced odds of high tHcy occurrence with 0.20 (95% confidence interval: 0.04-0.98) and 0.14 (95% confidence interval: 0.03-0.64), respectively. In conclusion, nutrition-related methyl-group insufficiency could lead to imbalance in tHcy metabolism, as a possible cancer marker.

Association of folate and other one-carbon related nutrients with hypermethylation status and expression of RARB, BRCA1, and RASSF1A genes in breast cancer patients

“…The present FFQ was validated for 136 food items to ascertain relatively precise estimates of nutrients in one-carbon metabolism [16,[21][22][23]; however, most previous studies having inconclusive results neglected to administer a validated FFQ or did not validate the FFQ for their own populations. The validity test is important because there is an overriding concern about misclassification of one-carbon nutrients from generally used questionnaires.…”

“…A growing body of evidence addresses the links between onecarbon metabolism and aberrant DNA methylation [13,14]. Folate as 5-methyl-tetrahydrofolate (5-methyl-THF) is a methyl donor that regenerates methionine from homocysteine to support S-adenosylmethionine (SAM)-dependent biological transmethylation reactions [15,16]. Nevertheless, some randomized clinical trials have shown that folate supplementation may increase genomic methylation density, and insufficient folate intake may play a role in defected methylation maintenance regulating upstreams of some genes [9,14].…”

“…No data exists to show the possible interactions between the certain nutrient and hypermethylation of RARB, BRCA1, or RASSF1A gene [15,20]. Defeated cellular bioavailability of cobalamin (vitamin B 12 ) leads to functional methionine synthase (MS) deficiency and yields, in part, hyperhomocysteinemia [16]. Pyridoxine (vitamin B 6 ) plays a crucial role as coenzyme of glycine hydroxymethyltransferase to compensate for the role of MS to intensify SAM/SAH ratio [13].…”

Inflammatory potential of diet in association with breast cancer risk: A matched case-control study

“…Dietary data were collected using a validated semi-quantitative 136-item food frequency questionnaire (FFQ) (31)(32)(33)(34). Portion sizes and frequency of consumption were requested for each food item on a daily, weekly, monthly, or yearly basis.…”

Association of Serum Homocysteine in Diabetic Neuropathy

“…Hyperhomocysteinemia is a condition where serum HCY level is above 15 µmol/L [8]. When any one of the Vitamin B 12 , Vitamin B 6 , and folic acid deficiency occurs, plasma HCY levels increase in the body [9].…”