Relationship between folate status and tumour progression in patients with hepatocellular carcinoma.
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.
Kuo
Chang-Sheng
CS
Department of Nutritional Science, Fu Jen University, Hsin-Chuang 242, Taiwan.
Lin
Ching-Yih
CY
Wu
Meng-Ying
MY
Lu
Chin-Li
CL
Huang
Rwei-Fen
RF
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005494:Folic Acid Deficiency / Q000097:blood* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009752:Nutritional Status; D016017:Odds Ratio; D011446:Prospective Studies; D012306:Risk; D000509:alpha-Fetoproteins / Q000032:analysis
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; D005492:Folic Acid