Endometrial Cancer In Folate Perspective

Posted by Chantel Martiromo

The incidence of endometrial cancer among white women are higher in comparison of black. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.

Folate, also known as folic acid, vitamin B9, is a water soluble vitamin, found abundantly in leafy vegetables, citrus fruits, beans, whole grain, etc. The vitamin plays an important role in synthesize, repair, and methylate DNA as well as to act as a cofactor in certain biological reactions, production of red blood cells for anemia prevention.

Epidemiological studies, focusing Folate receptor alpha (FRA) in diagnosis of  risk and  dietary in reduced risk of endometrial cancer have been inconclusive. Folate receptor alpha (FRA)  can be overexpressed by a number of epithelial-derived tumors including ovarian, breast, renal, lung, colorectal, and brain, the study emphasized the correlation of the receptor expression in endometrial cancer showed no significant difference in women with endometrial cancer after chemotherapy(1) but an associated growth advantage, rather than the process of tumorigenesis resulting in aberrant expression of FRA per se.(2). But in  "high risk" endometrial carcinomas, Moderate/strong FRalpha staining was significantly associated with other poor prognostic factors including: advanced stage, nonendometrioid histology and high grade of the diseases(3)
One-carbon metabolism dietary factors, including levels of folate, choline, methionine, vitamin B2, vitamin B6 or vitamin B12, do not effect the endometrial incidence(4). But in Type I and II endometrial cancer study, intake of use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.(5). The Folate (FOL) mediated poly-lactide-co-glycolide-polyethylene glycol nanoparticles (FOL-PEG-PLGA NPs) bearing paclitaxel (PTX),  was found to be effective in  indcution of cytotoxicity against HEC-1A cancer cells in vitro and in vivo, through possibly induced apoptosis(6). The joint study of the effects of dietary folate and other methyl-related nutrients, as well as three polymorphisms of MTHFR (677C>T, 1298A>C, and 1793G>A), on endometrial cancer risk among women between the ages of 30 and 69 years in urban Shanghai, China, showed an inverse association of folate intake and risk of endometrial cancer and modufied effects in women with encode gene MTHFR polymorphisms(plays a role in processing amino acids, the building blocks of proteins)(7).

Taking altogether, without going into reviews, dietary folate may associate to reduced risk and treatment of endometrial cancer, but multi centers studies are necessary to validate its effectiveness with large example size. Overdoses of folate may cause stomach problems, sleep problems, skin reactions, seizures, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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 References
(1) Folate receptor alpha (FRA) expression remains unchanged in epithelial ovarian and endometrial cancer after chemotherapy by Despierre E¹, Lambrechts S, Leunen K, Berteloot P, Neven P, Amant F, O'Shannessy DJ, Somers EB, Vergote I.(PubMed)
(2) Expression of folate receptor-α (FRA) in gynecologic malignancies and its relationship to the tumor type by O'Shannessy DJ¹, Somers EB, Smale R, Fu YS.(PubMed)
(3) Rationale for folate receptor alpha targeted therapy in "high risk" endometrial carcinomas.

Brown Jones M¹, Neuper C, Clayton A, Mariani A, Konecny G, Thomas MB, Keeney G, Hartmann L, Podratz KC.(PubMed)

(4) One-carbon metabolism factors and endometrial cancer risk by Liu JJ¹, Hazra A, Giovannucci E, Hankinson SE, Rosner B, De Vivo I.(PubMed)
(5) Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: a prospective cohort study by Uccella S¹, Mariani A, Wang AH, Vierkant RA, Robien K, Anderson KE, Cerhan JR.(PubMed)
(6) Improved therapeutic effect of folate-decorated PLGA-PEG nanoparticles for endometrial carcinoma by Liang C¹, Yang Y, Ling Y, Huang Y, Li T, Li X.(PubMed)
(7) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women by Xu WH¹, Shrubsole MJ, Xiang YB, Cai Q, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO(PubMed)