ABSTRACT
A novel allele, HLA-B*4456N, was identified upon cloning and sequencing of genomic DNA.
Subject(s)
Genome, Human , HLA-B Antigens/genetics , Alleles , Amino Acid Substitution/genetics , Base Sequence , Humans , Molecular Sequence Data , Sequence Alignment , Sequence Analysis, DNASubject(s)
Alleles , Exons , HLA-DR Antigens/genetics , Sequence Analysis, DNA , Base Sequence , Exons/immunology , HLA-DRB1 Chains , Humans , Molecular Sequence DataSubject(s)
Exons/genetics , HLA-DR Antigens/genetics , Sequence Analysis, DNA , Alleles , Base Sequence , HLA-DRB1 Chains , Humans , Molecular Sequence DataSubject(s)
Carcinoma, Renal Cell/genetics , Genetic Predisposition to Disease , Kidney Neoplasms/genetics , Ligases/genetics , Mutation , Tumor Suppressor Proteins , Ubiquitin-Protein Ligases , Aged , Carcinoma, Renal Cell/epidemiology , Carcinoma, Renal Cell/etiology , Cohort Studies , Female , Humans , Incidence , Kidney Neoplasms/epidemiology , Kidney Neoplasms/etiology , Male , Middle Aged , Netherlands/epidemiology , Polymorphism, Genetic , Polymorphism, Single-Stranded Conformational , Risk Factors , Sex Factors , Surveys and Questionnaires , Von Hippel-Lindau Tumor Suppressor ProteinABSTRACT
OBJECTIVES: The polymorphic enzyme alcohol dehydrogenase (ADH) catalyses the conversion of ethanol into the carcinogenic metabolite acetaldehyde which is partly excreted into the urine. Objectives of this pilot study are to determine whether this polymorphism may be related to bladder cancer and whether it modifies the relation between alcohol intake and bladder cancer. METHODS: 120 bladder cancer patients and 133 convenience controls were recruited at the University Medical Centre Nijmegen. A self-administered questionnaire was used to assess alcohol intake and potential confounders. DNA was isolated from peripheral blood, and ADH3 genotype was determined using PCR/RFLP. People with the ADH3 genotype gamma1gamma1 were compared to people with other ADH3 genotypes. Above moderate drinkers (>14 glasses of alcohol per week) were compared to moderate drinkers. Odds ratios (ORs) and 95% confidence intervals were computed using logistic regression analyses. RESULTS: After correction for sex, age and smoking, ORs for ADH3 genotype and alcohol intake were 2.10 (1.05-4.22) and 1.21 (0.60-2.44), respectively. Moderate drinkers with the 'high-risk' (gamma1gamma1) ADH3 genotype appeared to have a threefold higher risk of bladder cancer compared to moderate drinkers with a 'low-risk' (gamma1gamma2 or gamma2gamma2) genotype. Surprisingly, the ORs for above moderate drinkers with the low-risk genotype (1.95; 95% CI: 0.85-4.48) and with the high-risk genotype (2.18; 95% CI: 0.82-5.77) were almost similar, suggesting no interaction. CONCLUSIONS: ADH3 genotype is a possible risk factor for bladder cancer. Although moderate drinkers with the gamma1gamma1 genotype seem to have the highest risk, we did not get a clear indication that ADH3 genotype modifies the relationship between alcohol intake and bladder cancer.
Subject(s)
Alcohol Dehydrogenase/genetics , Alcohol Drinking/adverse effects , Ethanol/metabolism , Urinary Bladder Neoplasms/genetics , Aged , Female , Genotype , Humans , Logistic Models , Male , Middle Aged , Pilot Projects , Risk Factors , Surveys and Questionnaires , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/epidemiologyABSTRACT
OBJECTIVE: Little is known about risk factors for the development of benign prostatic hyperplasia (BPH). Recently, associations were observed between prostate cancer (CaP) risk and polymorphisms in the vitamin D receptor (VDR) gene and the androgen receptor (AR) gene. Since both receptors are relevant for prostate growth, the VDR and AR are also expected to be involved in the development of BPH. The objective of this study is to establish the relationship between the risk of BPH and a polymorphism in the number of CAG repeats in the AR gene and a TaqI restriction enzyme polymorphism in the VDR gene. METHODS: For this study, 98 patients who had been treated for BPH-related complaints and 61 convenience controls (predominantly bladder cancer patients) were recruited from the outpatient clinic. DNA was isolated from peripheral blood, and genotyping was performed with PCR-based methods. Means as well as odds ratios (ORs) with 95% confidence intervals (CI) were calculated using SPSS software. RESULTS: The mean number of CAG repeats in the AR gene in patients and controls was found to be similar: 21.8 (SD = 2.8) and 21.9 (SD = 2.9), respectively. In the subgroup of patients with a prostate volume of at least 50 cm(3), the mean number of repeats was 21.5 (SD = 2.6). The OR for BPH for individuals with homozygous presence of the VDR TaqI restriction fragment length polymorphism (RFLP) (tt) versus individuals with homozygous absence (TT) or heterozygotes (Tt) was found to be 1.0 (95% CI 0.4-2.4). For individuals with a prostate volume of at least 50 cm(3), the OR was 1.2 (95% CI 0.5-3. 2). CONCLUSION: Unlike earlier observations in prostate cancer, we did not find an association between the CAG repeat polymorphism in the AR gene and the TaqI RFLP polymorphism in the VDR gene and the risk of BPH.
