Abstract
Previous studies with folate/methyl-deficient rat models proposed the role of folate deficiency in hepatocarcinogenesis and tumour progression. We investigated the relationship between folate status and tumour progression in patients with hepatocellular carcinoma (HCC). Ninety HCC patients (age 62 (sd 10) years) recruited through the Department of Internal Medicine, Chi-Mei Hospital, participated in this cross-sectional study. According to the clinical criteria, 44 % showed marginal folate deficiency (serum folate 7-14 nmol/l; folate intake 278 (sd 212) microg/d), and 16 % were folate deficient ( < 7 nmol/l; 207 (sd 113) microg/d). Serum folate showed inverse correlations with three elements of tumour progression: tumour size (r - 0.29; P = 0.005), tumour multiplicity (r - 0.24; P = 0.018) and metastasis (r - 0.39; P = 0.0001). When HCC progression was categorised into stages I to IV, serum folate decreased as HCC stage progressed (stage I, 24.5 (sd 11.5); stage IV, 10.3 (sd 3.3) nmol/l; P = 0.032). After adjustment for age, sex, lifestyle and dietary factors, patients with low blood folate status (serum folate < 14 nmol/l) had increased risks for advanced tumour progression in large tumours (OR 7.1 (95 % CI 2.27, 21.9); P = 0.0007), tumour multiplicity (OR 3.2 (95 % CI 1.07, 3.51); P = 0.004) and metastasis (OR 4.5 (95 % CI 1.11, 18.4); P = 0.03) relative to those with normal folate status. Further controlling for liver injury, tumour proliferation and tumour stage, however, negated the effect of folate on advanced tumour progression. The data thus suggest that low blood folate status could be a risk factor for tumour progression, which is modulated by clinical lesions present in HCC patients. Future studies with larger sample sizes are warranted to explore the joint effects of low folate and hepatic lesions in human HCC malignancy.
Highlights
Previous studies with folate/methyl-deficient rat models proposed the role of folate deficiency in hepatocarcinogenesis and tumour progression
The data suggest that low blood folate status could be a risk factor for tumour progression, which is modulated by clinical lesions present in hepatocellular carcinoma (HCC) patients
The low serum folate levels were not associated with changes in BMI, levels of albumin, Hb, glutamic-oxaloacetic transaminase (GOT) or alanine aminotransferase (ALT), or liver cirrhosis (Tables 2 and 3)
Summary
Previous studies with folate/methyl-deficient rat models proposed the role of folate deficiency in hepatocarcinogenesis and tumour progression. After adjustment for age, sex, lifestyle and dietary factors, patients with low blood folate status (serum folate , 14 nmol/l) had increased risks for advanced tumour progression in large tumours (OR 7·1 (95 % CI 2·27, 21·9); P1⁄4 0·0007), tumour multiplicity (OR 3·2 (95 % CI 1·07, 3·51); P1⁄4 0·004) and metastasis (OR 4·5 (95 % CI 1·11, 18·4); P1⁄4 0·03) relative to those with normal folate status. An adequate folate status supplies the liver with available one-carbon carriers for de novo thymidylate and purine synthesis, amino acid interconversion and methylation of macromolecules[7] Chronic liver diseases such as viral hepatitis[8,9], alcoholic liver disorder[10] and liver cirrhosis(11 – 13) may compromise the folate status, as low blood folate levels are commonly found in patients with those diseases.
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