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PubMed2006

Common genetic polymorphisms and prognosis of sporadic cancers: prostate cancer as a model.

To date, most molecular epidemiological studies on gene polymorphisms in cancer have focused on the risk of development and susceptibility to cancer. However, interindividual genetic variation may contribute greatly to the treatment outcome and prognosis of cancer by affecting the interaction between cancer cells and hormones, growth factors and factors influencing the tumor microenvironment. In prostate cancer, several recent molecular epidemiological studies suggested the possibility of predicting treatment outcome and prognosis using genetic polymorphisms. Candidate genes are hormone-related, oncogenes, tumor-suppressor and cell cycle-growth control-related genes, as well as genes related to immune response, inflammatory change, neovasculization, and the extracellular matrix, genes involved in drug and xenobiotic metabolism and genes involved in DNA repair and genome stability. There remain a huge number of candidate genes whose polymorphisms may affect the progression and treatment outcome of various kinds of cancer, including that of prostate cancer.

Genetic Predisposition to Disease↗
PubMed1985

Purification and characterization of the human liver cytochromes P-450 involved in debrisoquine 4-hydroxylation and phenacetin O-deethylation, two prototypes for genetic polymorphism in oxidative drug metabolism.

Two forms of cytochrome P-450 were purified to apparent homogeneity from several different preparations of human liver microsomes. One form, designated P-450DB, had relatively high catalytic activity towards the drugs debrisoquine, sparteine, bufuralol (both the (+)- and (-)-isomers), encainide, and propranolol and appears to be the enzyme involved in the polymorphic distribution of oxidative activities towards these substrates in humans. The other form, designated P-450PA, had relatively high phenacetin O-deethylase activity and appears to be involved in the variation of this activity among humans. Polyclonal antibodies raised to the two enzymes were specific for the antigens as judged by immunoelectrophoresis and immuno-inhibition studies. The two enzymes and their activities were distinguished by chromatographic separation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, amino acid composition, immuno-inhibition studies, and steady-state kinetic assays. Immunochemical studies suggest that each form represents only a small fraction of the total cytochrome P-450 in human liver microsomes. These biochemical studies provide a basis for better understanding the mechanisms which underlie genetic polymorphisms involving P-450 cytochromes in humans.

Amino Acids↗
PubMed1999

Genetic polymorphisms of the renin-angiotensin system and atheromatous renal artery stenosis.

Genes that influence the renin-angiotensin system have been investigated in recent years as potential etiologic candidates of cardiovascular and renal diseases. In atheromatous renal artery stenosis (RAS), a condition characterized by persistent activation of the renin-angiotensin system, the study of these genes may be of particular relevance. We evaluated angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, and angiotensin II receptor (ATR) A1166C polymorphisms in relation to the occurrence of RAS. We studied 58 patients with angiographically documented RAS; 102 normotensive subjects with normal coronary arteries and no history or clinical or instrumental evidence of atherosclerosis in other vascular districts were considered the control group. Patients had a significantly higher D allele frequency (0.70 versus 0.55; chi(2) 6.88, P=0.01; odds ratio [OR] 1. 9, 95% CI 1.17 to 3.07) than did the control population; 48.3% of patients were homozygous for DD (chi(2) 6.62, P<0.05; OR 2.04, 95% CI 1.05 to 3.95); and only 8.6% carried the II genotype (OR 0.34, 95% CI 0.19 to 1.47). No significant association was found for AGT M235T and ATR A1166C. Our results suggest a predisposing role for ACE genetic polymorphism in the development and progression of atheromatous RAS.

Adult↗
PubMed2001

MICA genetic polymorphism and linkage disequilibrium with HLA-B in 29 African-American families.

The human major histocompatibility complex (MHC) class I chain-related gene A ( MICA) is located 46 kb upstream of HLA-B and encodes a stress-inducible protein which displays a restricted pattern of tissue expression. MICA molecules interact with NKG2D, augmenting the activation of natural killer cells, CD8(+) alpha beta T cells, and gamma delta T cells. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. We investigated MICA allelic variations and linkage disequilibrium with HLA-A, B, and DRB1 loci on 110 parental haplotypes from 29 African-American families. PCR/sequence-specific oligonucleotide probing (SSOP) was used to define MICA polymorphisms in exons 2, 3, and 4. Ambiguous allelic combinations were resolved by sequencing exons 2, 3, and 4. Exon 5 polymorphisms were analyzed by size sequencing. For HLA-A, B and DRB1 typing, low-resolution PCR/SSOP and allelic PCR/sequence-specific priming techniques were used. Twelve MICA alleles were observed, the most frequent of which were MICA*008, MICA*004, and MICA*002, with gene frequencies of 28.2, 26.4, and 25.5%, respectively. Thirty-eight HLA-B- MICA haplotypic combinations were uncovered, 22 of which have not been reported in the HLA homozygous typing cell lines from the 10th International Histocompatibility Workshop. Significant positive linkage disequilibria were found in 8 HLA-B- MICA haplotypes. Furthermore, haplotypes bearing HLA-B*1503, *1801, *4901, *5201, *5301, and *5703 were found to segregate with at least two different MICA alleles. Our results provide new data about MICA genetic polymorphisms in African-Americans, which will form the basis for future studies of MICA alleles in allogeneic stem cell transplantation outcome.

Alleles↗
PubMed2005

Alterations of liver function test indices of filling station workers with respect of genetic polymorphisms of GSTM1 and GSTT1.

To determine the health effects of gasoline exposure on liver function test indices of filling station workers the present study was done. This case-control study was conducted in Shiraz on 56 male gasoline workers and 56 age- and sex-matched control subjects with no occupational exposure to gasoline. To elucidate the role of hepatic detoxifying enzymes, the genotypes of glutathione-S-transferases (GST) M1 and T1 were determined. Data analysis was done by multiple linear regression analysis and non-parametric Kruskal-Wallis test. The present study showed that all measurements were in normal range, although sub-clinical changes were detected in some indices. In liver function tests, exposure was associated with lower serum albumin (t=-3.88, P<0.001) and total proteins (t=-3.016, P=0.003) but higher alanine aminotransferase (t=2.856, P=0.005) and aspartate aminotransferase (t=2.11, P=0.038) levels in workers comparing to controls. Other investigators reported that GSTs involved in detoxification of several toxins including some of the compounds present in gasoline. Therefore, the possible influence of GSTT1 and GSTM1 genetic polymorphisms on alteration of liver function tests indices was investigated. The present findings showed that the genotype combinations of GSTM1 and GSTT1 did not alter the effects of exposure to gasoline in workers except for serum albumin. Serum albumin significantly decreased in workers with both active GST enzymes who had more than 5 years of employments (P=0.01). It is suggested that GSTM1 and GSTT1 are not involved in detoxification of toxicants present in gasoline which are hazardous to liver. Overall, due to detection of sub-clinical changes in hepatic test in gasoline station workers, exposure limitation and administrating safety device are recommended.

Adolescent↗
PubMed2004

[Genetic polymorphism of human immunodeficiency virus coreceptor CCR5Delta32 and CCR2-64I alleles in Chinese Yi Ethnic group in Sichuan].

OBJECTIVE: To explore genetic polymorphisms CCR5 of HIV coreceptor and CCR2 in Chinese Yi Ethnic group in Sichuan. METHODS: Genomic DNA samples were obtained from 119 healthy individuals and 88 HIV-1 infected individuals of Chinese Yi Ethnic group in Sichuan. Polymerase chain reaction (PCR), cloning and gene sequencing techniques were employed to identify the genotype of CCR5Delta32; PCR-restriction fragment length polymorphism (RFLP) and gene sequencing were employed to identify the CCR2-64I alleles. RESULTS: At CCR5 locus, 2 heterozygotes (CCR5-wt/Delta32) and none homozygote (CCR5-Delta32/Delta32) were observed in 119 healthy individuals, allelic frequency of CCR5-Delta32 was 0.84%; No mutant was found in 88 HIV-1 infected individuals. At CCR2 locus, 26 heterozygotes (CCR2-64V/64I) and two homozygotes (CCR2-64I/64I) were observed in healthy individuals but the allelic frequency CCR2-64I was 12.61%. Among infected individuals, 12 heterozygotes (CCR2-64V/64I) and 7 homozygotes (CCR2-64I/64I) were observed and the allelic frequency CCR2-64I was 13.27%. Statistical analysis revealed that the differences of both loci between healthy and infected individuals were insignificant. Both loci were consistent with the Hardy-Weinberg equilibrium in the two different groups. CONCLUSION: The polymorphism of CCR5Delta32 and CCR2-64I alleles from Chinese Yi Ethnic group was detected which was of significance for the evaluation of genetic resistance to HIV-1 infection in Chinese population.

Adult↗
PubMed2006

Implications of genetic polymorphisms in drug transporters for pharmacotherapy.

Drug transporters are increasingly recognized as a key determinant of drug disposition and response. It is now widely appreciated that expression of the ATP-dependent efflux transporter, MDR1 (ABCB1, P-glycoprotein), in organs such as the gastrointestinal tract, liver and kidney significantly alters the extent of drug absorption and excretion. Moreover, expression of MDR1 at the level of the blood-brain barrier limits the entry of many drugs into the central nervous system. Given such an important role of MDR1 in the drug disposition process, it is not surprising to see increasing focus on the role of single nucleotide polymorphisms (SNPs) in this transporter as a potential determinant of interindividual variability in drug disposition and pharmacological response. However, drug transport is often the result of the concerted action of efflux and uptake pumps located both in the basolateral and apical membranes of epithelial cells. A growing list of membrane-spanning proteins involved in the in- or outward transport of a large variety of drugs has been recognized and characterized over the past few years in almost all tissues, including organic anion and cation transporters (OAT, OCT, solute carrier family SLC22A), organic anion transport proteins (OATP, solute carrier family SLCO, formerly SLC21A), and MRPs (ABCCs), other members of the ATP-binding cassette family. We are just beginning to appreciate their role for drug delivery and disposition and the contribution of genetic polymorphisms in these transport proteins to interindividual variability in the efficacy and safety for pharmacotherapy. This review summarizes the consequences of inherited differences in drug transport for pharmacotherapy. With the main focus on ABCB1, an update of recent advances is given and clinically relevant examples are used to illustrate how heritable differential drug transport can help to explain individual variability in drug response. The pharmacogenetics of other transporters is briefly introduced.

ATP-Binding Cassette Transporters↗
PubMed2002

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms.

Factor XIII and fibrinogen are unusual among clotting factors in that neither is a serine protease. Fibrin is the main protein constituent of the blood clot, which is stabilized by factor XIIIa through an amide or isopeptide bond that ligates adjacent fibrin monomers. Many of the structural and functional features of factor XIII and fibrin(ogen) have been elucidated by protein and gene analysis, site-directed mutagenesis, and x-ray crystallography. However, some of the molecular aspects involved in the complex processes of insoluble fibrin formation in vivo and in vitro remain unresolved. The findings of a relationship between fibrinogen, factor XIII, and cardiovascular or other thrombotic disorders have focused much attention on these 2 proteins. Of particular interest are associations between common variations in the genes of factor XIII and altered risk profiles for thrombosis. Although there is much debate regarding these observations, the implications for our understanding of clot formation and therapeutic intervention may be of major importance. In this review, we have summarized recent findings on the structure and function of factor XIII. This is followed by a review of the effects of genetic polymorphisms on protein structure/function and their relationship to disease.

Blood Coagulation↗
PubMed1977

Genetic polymorphism of chicken 7S immunoglobulins.

A survey of 48 inbred lines derived from five sources in the United States and Europe revealed considerable genetic polymorphism of the CS-1 gene. A minimum of ten alleles were detected as unique combinations of CS-1 specificities. The relationship of some of the alleles would indicate that intracistronic recombination may have played a role in the production of some of the polymorphism.

Alleles↗
PubMed2001

Association of the interleukin-1 beta genetic polymorphism and gastric cancer risk in Japanese.

BACKGROUND: Helicobacter pylori infection is associated not only with gastroduodenal ulcers but with the development of gastric cancer. Interleukin-1 beta (IL-1 beta) is a potent inhibitor of gastric secretion. The -31 C-to-T base transition in the intron of this gene has been reported to be involved in carcinogenic changes within the stomach, especially in H. pylori-infected individuals. METHODS: In this study, the -511 T-to-C polymorphism in the IL-1 beta gene was investigated in 669 patients with gastric diseases. RESULTS: The allelic frequencies of the C allele, which indicates low acid secretion and is a component of a supposedly high-risk genotype for gastric cancer, were 0.48 in H. pylori-negative noncancer controls, 0.52 in H. pylori-positive noncancer controls, 0.57 in subjects with chronic active gastritis (CAG) with H. pylori, 0.58 in subjects with intestinal metaplasia (IM) or CAG without H. pylori, and 0.52 in gastric cancer patients. Significant differences among the groups were observed between the IM or CAG without H. pylori group and the gastric cancer group and between the IM or CAG without H. pylori group and the H. pylori-negative noncancer control group (P < 0.05). CONCLUSIONS: The IL-1 beta-511 genetic polymorphism was not associated with gastric cancer in a multistep carcinogenesis model. However, in view of the results for the IM or CAG without H. pylori group, the presence of the C allele may also indicate a risk of mucosal atrophy of the stomach in the Japanese population.

Genotype↗
PubMed2005

GSTT1, GSTM1 and GSTP1 genetic polymorphisms and interaction with tobacco, alcohol and occupational exposure in esophageal cancer patients from North India.

Glutathione S-transferases(GSTs) are detoxification enzymes that provide critical defense against carcinogens. Our hypothesis was that altered frequencies of GST genotypes and environmental exposures might be associated with increased susceptibility for the development of esophageal cancer. A total of 100 esophageal cancer patients and 137 age and gender matched healthy controls were analyzed for GST polymorphisms. Frequencies of GSTT1 null, GSTM1 null and GSTP1 genotypes did not differ between patients and controls. However, a two-fold risk was observed for GSTM1 null genotype in adenocarcinoma (OR(odds ratio) 2.1; 95% CI(confidence intervals)=0.53-8.6). Further, we used a case only design to study gene-environment interactions in esophageal cancer. In patients with smoking habits, GSTM1 null and GSTP1 ile/ile genotype were at higher risk for esophageal cancer (OR 1.5; 95% CI=0.50-4.4 and OR 1.3; 95% CI=0.40-3.5), respectively. A moderate risk for cancer was observed from alcohol usage along with GSTM1 null(OR 1.3; 95% CI=0.50-3.6) and GSTP1 val/val genotypes(OR 1.2; 95% CI=0.20-5.7). Interaction of GST genotypes with occupational exposure did not affect risk for esophageal cancer. These findings suggest that genetic polymorphisms of GSTT1, GSTM1, and GSTP1 are not associated with higher risk of esophageal cancer. However, interaction of smoking or alcohol with GSTM1 null or GSTP1 ile/ile moderately increases the risk for esophageal cancer in North Indian population.

Alcohol Drinking↗
PubMed1995

Characterization of apolipoproteins B-100, AI and C from plasma lipoprotein in the goose, Anser anser. Evidence for a genetic polymorphism in ApoC-like apolipoproteins.

In this study we have characterized four of the principle goose apolipoproteins and compared their physicochemical properties with human and avian counterparts. Goose ApoB-100 and ApoAI amino acid compositions were very similar to their chicken and human homologous proteins. The partial N-terminal sequence from goose ApoAI was 91% and 82% similar to the corresponding duck and chicken proteins, respectively. Most of the observed amino acid changes detected between the ApoAI sequences were amino acid replacements having the same characteristics and could be the result of a single base mutation. The N-terminal portion of two ApoC-like apolipoproteins were also studied. Goose ApoCa had an electrophoretic mobility of 0.31 and exhibited a nine-residue motif that was well conserved between ApoCIII sequences from different species. We therefore suggest that ApoCa is the equivalent of mammalian ApoCIII. The N-terminal portion of goose ApoCb, the second major ApoC in high-density apolipoprotein, showed no similarity to proteins previously described in the literature. This protein displayed two isomorphs in alkaline urea gel electrophoresis called ApoCb1 and ApoCb2 with Rf values of 0.36 and 0.39, respectively. A genetic polymorphism was detected in the population whereby 25% of the animals carried only one isomorph and 50% exhibited both ApoCb isomorphs. These frequencies were similar in females and males. The transmission mode of these ApoCb isomorphs was consistent with two segregating alleles from a single codominantly expressed gene.

Amino Acid Sequence↗
PubMed2005

Genetic polymorphism of glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India.

OBJECTIVE: To examine the association of glutathione-S-transferase (GST) gene polymorphisms in patients with sporadic prostate cancer, in a North Indian population, as GSTs are active in detoxifying a wide variety of endogenous or exogenous carcinogens, and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 have been assessed to evaluate the relative risk of various cancers. PATIENTS AND METHODS: We assessed 127 patients with prostate cancer and 144 age-matched controls, all from North India. The GSTT1 and GSTM1 null genotypes were identified by multiplex polymerase chain reaction (PCR) in peripheral blood DNA samples, and GSTP1-313 A/G polymorphism was determined by PCR/restriction fragment length polymorphism. RESULTS: There was a significant association in null alleles of the GSTM1 (odds ratio 2.239, 95% confidence interval 1.37-3.65, P = 0.001) and GSTT1 (1.891, 1.089-3.282, P = 0.026) with prostate cancer risk, and in the -313 G alleles (Val) of the GSTP1 gene (2.48, 1.51-4.08, P < 0.001). The combined analysis of these three genotypes showed a further increase in the risks of prostate cancer (7.23, 2.42-22.6, P < 0.001). CONCLUSION: The GSTP1-313 G polymorphism, and null alleles of GSTM1 and GSTT1, are strong predisposing risk factors for sporadic prostate cancer in North India.

Genetic Predisposition to Disease↗
PubMed1995

A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles.

A group of human cytochrome P450 genes encompassing the CYP2A, CYP2B, and CYP2F subfamilies were cloned and assembled into a 350-kb contig localized on the long arm of chromosome 19. Three complete CYP2A genes--CYP2A6, CYP2A7, and CYP2A13--plus two pseudogenes truncated after exon 5, were identified and sequenced. A variant CYP2A6 allele that differed from the corresponding CYP2A6 and CYP2A7 cDNAs previously sequenced was found and was designated CYP2A6v2. Sequence differences in the CYP2A6v2 gene are restricted to regions encompassing exons 3, 6, and 8, which bear sequence relatedness with the corresponding exons of the CYP2A7 gene, located downstream and centromeric of CYP2A6v2, suggesting recent gene-conversion events. The sequencing of all the CYP2A genes allowed the design of a PCR diagnostic test for the normal CYP2A6 allele, the CYP2A6v2 allele, and a variant--designated CYP2A6v1--that encodes an enzyme with a single inactivating amino acid change. These variant alleles were found in individuals who were deficient in their ability to metabolize the CYP2A6 probe drug coumarin. The allelic frequencies of CYP2A6v1 and CYP2A6v2 differed significantly between Caucasian, Asian, and African-American populations. These studies establish the existence of a new cytochrome P450 genetic polymorphism.

Alleles↗
PubMed1987

Enzymatic basis of the debrisoquine/sparteine-type genetic polymorphism of drug oxidation. Characterization of bufuralol 1'-hydroxylation in liver microsomes of in vivo phenotyped carriers of the genetic deficiency.

The genetically controlled polymorphic oxidation of debrisoquine and sparteine is caused by the absence or functional deficiency of a cytochrome P-450 isozyme. In order to elucidate the mechanisms underlying the differences in cytochrome P-450 function we have studied the 1'-hydroxylation of the prototype drug bufuralol in human liver microsomes of individuals phenotyped in vivo as extensive metabolizers (EM, N = 10), poor metabolizers (PM, N = 5) and in subjects with an intermediate rate of metabolism (IM, N = 4). PM- as compared to EM-microsomes were characterized by a decreased Vmax for (+)-bufuralol 1'-hydroxylation (7.51 +/- 2.03 nmol X mg-1 X hr-1 vs 11.95 +/- 4.80 nmol X mg-1 X hr-1) but not for (-)-bufuralol 1'-hydroxylation (4.72 +/- 0.87 nmol X mg-1 X hr-1 vs 5.55 +/- 1.49 nmol X mg-1 X hr-1). The apparent Km for (+)-bufuralol 1'-hydroxylation was increased in PM microsomes (118 +/- 84.9 microM vs 17.9 +/- 6.30 microM). Inhibition of bufuralol 1'-hydroxylation by quinidine was biphasic in EM microsomes, providing further support for the involvement of at least two cytochrome P-450 isozymes. Quinidine acted as a competitive inhibitor of only the high affinity/stereoselectivity component of the reaction. Our data suggest that the debrisoquine/sparteine type of oxidation polymorphism is caused by an almost complete loss of a minor cytochrome P-450 isozyme which has a high affinity and stereoselectivity for (+)-bufuralol and a high sensitivity to inhibition by quinidine.

Adult↗
PubMed2003

Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia.

Etoposide is a substrate for P-glycoprotein, CYP3A4, CYP3A5, and UGT1A1. Glucocorticoids modulate CYP3A and P-glycoprotein in preclinical models, but their effect on clinical etoposide disposition is unknown. We studied the pharmacokinetics of etoposide and its catechol metabolite in children with acute lymphoblastic leukemia, along with polymorphisms in CYP3A4, CYP3A5, MDR1, GSTP1, UGT1A1, and VDR. Plasma pharmacokinetics were assessed at day 29, after 1 month of prednisone (n = 102), and at week 54, without prednisone (n = 44). On day 29, etoposide clearance was higher (47.4 versus 29.2 mL/min/m2, P <.0001) than at week 54. The day 29 etoposide or catechol area under the curve (AUC) was correlated with neutropenia (P =.027 and P =.0008, respectively). The relationship between genotype and etoposide disposition differed by race and by prednisone use. The MDR1 exon 26 CC genotype predicted higher day 29 etoposide clearance (P =.002) for all patients, and the CYP3A5 AA and GSTP1 AA genotypes predicted lower clearance in blacks (P =.02 and.03, respectively). The UGT1A1 6/6, VDR intron 8 GG, and VDR Fok 1 CC genotypes predicted higher week 54 clearance in blacks (P =.039,.036, and.052, respectively). The UGT1A1 6/6 genotype predicted lower catechol AUC. Prednisone strongly induces etoposide clearance, genetic polymorphisms may predict the constitutive and induced clearance of etoposide, and the relationship between genotype and phenotype differs by race.

Base Sequence↗
PubMed2003

The effect of smoking and cytochrome P450 CYP1A2 genetic polymorphism on clozapine clearance and dose requirement.

Clozapine is an atypical antipsychotic drug that is metabolized to a major extent by the cytochrome P450 enzyme CYP1A2. Smoking is a potent inducer of CYP1A2 enzyme activity, resulting in significant lower clozapine serum concentrations in smokers compared with non-smokers, upon a given dose. Recently, a single nucleotide polymorphism identified at position 734 of the CYP1A2 gene, was reported to affect the inducibility of the enzyme. Because this polymorphism in relation to smoking behaviour may be relevant in treatment with clozapine, we studied the effect of CYP1A2 genotype on clozapine clearance and dose requirement in a group of 80 smoking and non-smoking schizophrenic patients on long-term clozapine therapy. Clozapine serum concentration and CYP1A2 genotype had been determined routinely by high-performance liquid chromatography and polymerase chain reaction analyses, respectively. In smokers, the clozapine serum concentration corrected for dose (C/D ratio) was on average 2.5 times lower compared with non-smokers, indicating an enhanced clearance. The mean required maintenance doses of clozapine for smokers and non-smokers were 382 mg/day and 197 mg/day, respectively (P < 0.01). Neither among smokers, nor among non-smokers mean C/D ratios and daily doses did vary significantly between patients with the different CYP1A2 genotypes. The results show that clozapine clearance and daily dose requirement are strongly associated with smoking behaviour, while the CYP1A2 genetic polymorphism seems to have no significant clinical effect. Dosage adjustment based on smoking behaviour would be of value in order to lower the incidence of non-therapeutic serum drug levels and, consequently, intoxication or inadequate antipsychotic response.

Adolescent↗
PubMed1996

Hepatocellular carcinoma associated with alcoholic liver disease: a clinicopathological study and genetic polymorphism of aldehyde dehydrogenase 2.

In this paper, we describe a clinicopathological study of primary hepatocellular carcinoma (HCC) associated with alcoholic liver disease without hepatitis virus infection. In 180 HCC patients who were admitted to Asahikawa Medical College Hospital from 1987 to 1995, 10 patients (6%) had HCC associated with pure alcoholic liver disease (Al-HCC), whereas the HCC in 165 patients was associated with chronic viral liver diseases, in 2 with primary biliary cirrhosis, in 1 each with coexistence of the hepatitis C virus infection and hemochromatosis, and in 2 with cirrhosis of unknown origin. In the Al-HCC group, all patients were male. The diagnosis of HCC was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Four cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in three cases and liver cirrhosis in seven cases. HCC was diagnosed histologically in all cases. Serum alpha-fetoprotein and PIVKA-II were positive in patients with advanced HCC. In cases with small HCC, the tumor was resected surgically in three cases and percutaneous ethanol injection was performed in two cases. In four cases with small HCC, the patients were alive without tumor recurrence during the observation period. In advanced HCC, transcatheter arterial chemolipiodolization was performed. In the analysis of genetic polymorphism of ALDH 2, all Al-HCC had ALDH 2(1)/2(1).

Aged↗