Hyperhomocysteinaemia and immune activation in patients with cancer

Recently, homocysteine production was observed in tumour cell lines and homocysteine was proposed as a tumour marker. Furthermore, homocysteine production by activated immunocompetent cells was demonstrated.

In this study, homocysteine metabolism and immune activation status were investigated in 128 patients suffering from various types of cancer (haematological disorders, lung cancer, gastrointestinal tumours, gynaecological cancer and tumours of other localisation) and healthy age-matched controls.

A high percentage of patients (39.1%) showed moderate hyperhomocysteinaemia, while cysteine, folate and vitamin B(12) concentrations were within reference ranges. Most patients were found to have elevated concentrations of the immune activation and inflammation markers neopterin and C-reactive protein (CRP), as well as a higher erythrocyte sedimentation rate (ESR). Patients of different cancer groups differed significantly regarding vitamin B(12) and neopterin concentrations; higher B(12) levels were also associated with tumour progression. Univariate regression analysis showed that CRP, ESR and neopterin were suited best to predict death. In multivariate analysis, neopterin was best suited to predicting death, while homocysteine and B vitamins were not associated with patient outcome. Homocysteine concentrations were correlated with folate and cysteine levels. Higher neopterin concentrations coincided with lower folate concentrations, but higher vitamin B(12) concentrations.

Associations between neopterin and folate concentrations may indicate that cellular immune activation might partly contribute to the development of folate deficiency in cancer patients, thus possibly also impairing homocysteine remethylation.