1. ¹Breast Surgery Unit, Belfast City Hospital, Lisburn Road, Belfast, N Ireland BT9 7AB, UK
2. ²Breast Surgery Unit, Level 3 west, Norfolk and Norwich University Hospitals, Colney Lane, Norwich, NR4 7UY, UK
3. ³School of Biomedical Science, University of Ulster, Coleraine, N Ireland, UK
4. ⁴Center for Cancer Research and Cell Biology, Queen's University, Belfast, N Ireland, UK
5. ⁵College of Science and Technology, The Nottingham Trent University, Nottingham, England, UK

Correspondence: Dr MMI Hussien, Breast Surgery Unit, Level 3 west, Norfolk and Norwich University Hospitals, Colney Lane, Norwich, NR4 7UY, UK. E-mail: magedhussien@hotmail.com

Received 14 September 2004; Revised 9 February 2005; Accepted 28 February 2005; Published online 5 April 2005.

Abstract

Folate is required for DNA synthesis, repair and methylation. Low folate status has been implicated in carcinogenesis, possibly as a result of higher rate of genetic damage. The aim of this study is to compare folate status and levels of DNA damage between breast cancer and benign breast disease control patients. Fasting blood samples from 64 histologically confirmed untreated breast cancer patients (mean age 57 years) and 30 benign breast disease control patients (mean age 51 years) were obtained. Red cell folate (RCF) and plasma homocysteine were measured. Mononuclear cells (MNC) were isolated for genetic damage analysis using the basic alkaline comet assay. Results are expressed as tail moment. Data were log transformed as appropriate before analysis for normalisation purposes. The geometric mean (95% confidence interval) of RCF (ng ml^-1) in breast cancer patients was 339.07 (333.3–404.6) vs 379.5 (335.8–505.2) in control patients (P=0.24). Corresponding plasma homocysteine concentrations (mol l^-1) were 11.9 (10.6–16.4) vs 10.1 (9.3–11.9) (P=0.073), respectively. The mean tail moment (s.d.) of DNA damage in MNC of breast cancer patients detected by the basic comet assay was 1.4 (0.66) vs –0.17 (0.79) in controls (P<0.0001, t-test), the modified comet assay 'endonuclease III (Endo III)' was 1.7 (0.70) vs 0.86 (0.81) (P<0.0001, t-test), and the modified comet assay 'formamidopyrimidine glycosylase (FPG)' was 1.6 (0.62) vs 0.99 (0.94) (P<0.0001, t-test). There was a significant negative correlation between RCF levels and DNA damage detected by modified comet assay 'FPG' (Pearson Correlation Coefficient r²=-0.26, P=0.02) and DNA damage was found to be significantly higher in MNC of breast cancer patients compared to benign breast disease control patients. Breast cancer patients tended to have lower RCF levels and higher levels of plasma homocysteine, but these differences were not significant. The study provides preliminary evidence that reduced folate status may be implicated in the aetiology of breast cancer perhaps by increasing the in vivo level of genetic instability.