Chemopreventative Role

Epidemiological, animal and human studies all suggest that folate status affects the risk of developing cancers in selected tissues. The exact nature of this relationship continues to elude researchers (Bollheimer et al 2005, Powers 2005). Previously, high folate intake was purported to have a protective effect, although there were some anomalies. An extensive review of the role of the MTHFR C677T polymorphism in cancer risk concluded that, in spite of the poor folate status and activity associated with this polymorphism, many studies identify it as protective against a range of cancers (Sharp & Little 2004). To add to this a group of Swedish researchers have demonstrated that the relationship between serum folate and colorectal cancer follows a bell-shaped curve distribution (Van Guelpen et al 2006). Speculation regarding the role of additional co-factors involved in folate activity has also emerged (Powers 2005).

However, folate's actions still represent a plausible modulator of cancer risk due to its critical role in the production, methylation and repair of DNA, regulation of cell turnover and suppression of excessive proliferation (Choi et al 2000, 2002). Colon cancer The link between folate status and colorectal cancer was first suggested in the 1990s when clinical studies identified an inverse association between folate and colorectal carcinogenesis. Subsequent rodent studies further strengthened the theory when chemically induced colorectal carcinogenesis was shown to be tremendously enhanced under dietary folate deprivation and reduced with folate administration (Cravo et al 1992, Kim et al 1996).

In 2005, a major review of In vitro, animal and various clinical and epidemiological studies concluded that high folate Intake does not lead to an Independent, overall chemopreventatlve effect on colorectal carcinogenesis, although results from two large studies suggest that folate deficiency might have a particular Impact on proximal colon cancer In females (Bollhelmer et al 2005).

Since then, a recent study demonstrated Improved response In patients with adenomatous polyps using a combination of 100 fjg of folate and 5 mg riboflavin over folate alone (Powers 2005).

Cervical cancer The potential role of folate In the prevention of cervical cancer has been equivocal and results from Intervention studies on cervical cancer have been Inconsistent (Henao et al 2005, Kwanbunjan et al 2005, Sedjo et al 2003). Many of these studies have methodological limitations, Including a lack of Information on high-risk human papillomavirus (HR-HPV) Infection, a risk factor for cervical cancer. This Is notable as folate deficiency may Increase the risk of cervical cancer In Individuals Infected with HR-HPV (Plyathllake et al 2004).

The most promising RCT Involved 47 patients taking an OCP who demonstrated mild to moderate Intraepithelial dysplasia. A dose of 10 mg folic acid dally over 3 months resulted In significantly lower biopsy scores In the treatment group and a significant reduction In cytology scores from baseline (Butterworth et al 1982). Other studies have shown that folic acid treatment does not alter the course of disease In patients with pre-established cervical dysplasia (Chllders et al 1995).

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