retinol-palmitate and Carcinoma--Non-Small-Cell-Lung

The neutrophil-to-lymphocyte ratio (NLR) is a biomarker that indicates systemic inflammation and can be estimated using array-based DNA methylation data as methylation-derived NLR (mdNLR). We assessed the relationship between prediagnosis mdNLR and lung cancer risk in a nested case-control study in the β-Carotene and Retinol Efficacy Trial (CARET) of individuals at high risk for lung cancer due to heavy smoking or substantial occupational asbestos exposure. We matched 319 incident lung cancer cases to controls based on age at blood draw, smoking, sex, race, asbestos, enrollment year, and time at risk. We computed mdNLR using the ratio of predicted granulocyte and lymphocyte proportions derived from DNA methylation signatures in whole blood collected prior to diagnosis (median 4.4 years in cases). Mean mdNLR was higher in cases than controls (2.06 vs. 1.86,

Topics: Aged; Asbestos; beta Carotene; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Diterpenes; DNA Methylation; Female; Humans; Inflammation; Lung Neoplasms; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Occupational Exposure; Oligonucleotide Array Sequence Analysis; Retinyl Esters; Risk Factors; Smokers; Smoking; Vitamin A

Vitamin A and retinoids are strong inhibitors of epithelial cancer promotion and progression in experimental carcinogenesis. This study examined whether they may prevent the occurrence of upper aerodigestive cancer in subjects heavily exposed to tobacco smoking, such as patients already cured of an early-stage lung cancer.. The adjuvant effect of high-dose vitamin A was tested on 307 patients with stage I non-small-cell lung cancer. After curative surgery, patients were randomly assigned to either a group prescribed retinol palmitate administration (orally 300,000 IU daily for 12 months) or a control group prescribed no treatment.. After a median follow-up of 46 months, the number of patients with either recurrence or new primary tumors was 56 (37%) in the treated arm and 75 (48%) in the control arm. Eighteen patients in the treated group developed a second primary tumor, and 29 patients in the control group developed 33 second primary tumors. A statistically significant difference in favor of treatment was observed concerning time to new primary tumors in the field of prevention (P = .045, log-rank test). The treatment difference in terms of disease-free interval was close to statistical significance (P = .054, log-rank test) and just significant when adjusted for primary tumor classification (P = .038, Cox regression model).. Daily oral administration of high-dose vitamin A is effective in reducing the number of new primary tumors related to tobacco consumption and may improve the disease-free interval in patients curatively resected for stage I lung cancer. The impact of such a treatment on survival needs to be further explored.

Topics: Adolescent; Adult; Anticarcinogenic Agents; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Child; Child, Preschool; Diterpenes; Female; Humans; Infant; Lung Neoplasms; Male; Middle Aged; Neoplasms, Second Primary; Patient Compliance; Recurrence; Retinyl Esters; Survival Analysis; Vitamin A

The laboratory findings in patients receiving high-dose vitamin A as adjuvant treatment for stage I lung cancer are here reported. A group of 283 patients were randomized to either treatment with retinyl palmitate (300,000 IU daily for 12 months) or standard follow-up, and are now evaluable after a median observation period of 28 months. At regular intervals, all the patients underwent a physical examination, chest roentgenogram, blood chemistries, haematological assays, hepatic and renal function tests and determinations of serum triglycerides and cholesterol. Serum transaminase abnormalities were of similar magnitude in cases and controls, while gamma-glutamyltransferase levels were abnormally elevated in 69% of the treated patients compared to 39% of controls (mean values 149 vs 57 IU/l at 24 months, P less than 0.05). Serum triglyceride concentrations over 150 mg/dl were seen in 74% of treated patients compared to 43% of controls at 12 months, the average concentration was 283 mg/dl compared to 179 mg/dl (P less than 0.05). Cholesterol levels showed a modest, non-significant rise with time in both groups, and there was no other laboratory evidence of toxicity attributable to vitamin A. Serum retinol and retinol-binding protein, assessed on a limited sample of patients, were higher in the treatment arm (P less than 0.05) at 12 months. In our experience 300,000 IU/day of retinyl palmitate can be administered as a possible chemopreventive agent with reasonable safety for up to 2 years.

Topics: Aspartate Aminotransferases; Blood Cell Count; Blood Urea Nitrogen; Carcinoma, Non-Small-Cell Lung; Cholesterol; Diterpenes; Drug Evaluation; Female; gamma-Glutamyltransferase; Humans; Liver; Lung Neoplasms; Male; Prealbumin; Retinol-Binding Proteins; Retinyl Esters; Triglycerides; Vitamin A

Epidemiological studies have shown an inverse relationship between dietary vitamin A intake and the risk of developing lung cancer. The aim of this study was to investigate the vitamin A status in patients with lung cancer, by determining the serum levels of retinoic acid, retinol and retinyl palmitate.. In total, 36 patients with lung cancer and 27 controls were assessed. Of the patients 14 had squamous cell carcinoma, 3 adenocarcinoma, 15 non-small cell lung cancer and 4 small cell lung cancer. Serum retinoic acid, retinol and retinyl palmitate levels were determined with HPLC and UV detection, after liquid extraction.. Serum retinol levels did not differ between patients (733.5 +/- 326.4 ng/mL) and controls (734.5 +/- 337.1 ng/mL). The retinyl palmitate concentration tended to be lower in patients (14.3 +/- 9.7 ng/mL) than in controls (16.7 +/- 13.7 ng/mL). The serum retinoic acid levels were significantly lower in patients (1.9 +/- 0.6 ng/mL) than in controls (2.5 +/- 1.1 ng/mL, P < 0.05). A positive correlation was observed between the retinol and retinoic acid levels and retinyl palmitate and retinoic acid levels.. The lower levels of retinoic acid in patients with lung cancer suggest there may be a deficiency or impairment in retinol metabolism in these patients. Further studies with larger numbers of patients are needed to evaluate the possible relationship between serum retinoid levels and lung cancer.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromatography, High Pressure Liquid; Disease Progression; Diterpenes; Female; Humans; Lung Neoplasms; Male; Prognosis; Retinyl Esters; Risk Factors; Tretinoin; Vitamin A