Re: Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer.

Abstract

We read with great interest the article by Zhang et al. (1) in which they examined the association of plasma folate, vitamin B6, vitamin B12, and homocysteine with the risk of breast cancer. Although high plasma folate and vitamin B12 concentrations were associated with a lower risk of breast cancer, plasma homocysteine concentration was not associated with risk. This finding seems to contradict the recently suggested role of homocysteine as a potential tumor marker (2,3). In vitro, tumor cells and other proliferating cells release homocysteine (2,3), which might explain why hyperhomocysteinemia is observed in patients with various kinds of cancers. Plasma homocysteine and neopterin concentrations are closely associated with each other in patients with various types of diseases (4). In cancer patients, increased urine and plasma neopterin concentrations have been reported (5,6), which suggest enhanced cellular immune activation. Within cellular immune activation, T cells release large amounts of the cytokine interferon, which stimulates human monocyte-derived macrophages and dendritic cells to produce neopterin (7). Immune activation cascades and proliferation and stimulation of immunocompetent cells could also be important in the accumulation of plasma homocysteine in various diseases, including malignancies. When different tumors are compared, the frequency of increased neopterin concentration is much lower in patients with breast cancer than it is in patients with other types of cancers (5). Indeed, less than 20% of patients with breast cancer present with neopterin levels above normal. Although no association between neopterin and tumor size or lymph node status has been shown in women with breast cancer, follow-up examinations reveal that higher urine neopterin concentrations at diagnosis are associated with shorter survival (6). The finding that plasma homocysteine concentrations, like neopterin concentrations, are only rarely elevated in breast cancer patients further supports the notion that immune activation and proliferation of immunocompetant cells rather than tumor cell proliferation is the explanation for hyperhomocysteinemia in cancer patients.