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PubMed2005

A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C.

BACKGROUND: There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteria based on histology at biopsy in addition to disease duration would be more likely to inherit several genetic polymorphisms associated with disease progression compared with subjects with a low rate of disease progression. METHODS: We examined polymorphisms in eight genes that have been reported to have an association with hepatic fibrosis. RESULTS: Associations between polymorphisms in six genes and more rapidly progressing fibrosis were observed, with individual adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly progressing fibrosis and possession of > or =3, > or =4, or > or =5 progression associated alleles was determined and the adjusted odds ratios increased with increasing number of progression associated alleles (9.1, 15.5, and 24.1, respectively). Using logistic regression analysis, a predictive equation was developed and tested using a second cohort of patients with rapidly progressing fibrosis. The predictive equation correctly classified 80% of patients in this second cohort. CONCLUSIONS: This approach may allow determination of a genetic profile predictive of rapid disease progression in HCV and identify patients warranting more aggressive therapeutic management.

Adult↗
PubMed1997

CYP2D6, NAT2 and CYP2E1 genetic polymorphisms in nonagenarians.

BACKGROUND: enzymatic polymorphisms affecting the metabolic disposition of xenobiotics may modulate the rate of activation or deactivation of carcinogens and other toxic environmental chemicals. Hence, these polymorphisms may influence the risk of suffering some types of cancer and other degenerative diseases that are incompatible with extreme longevity. AIMS: to establish the distribution of three well known enzymatic polymorphisms that affect the CYP2D6, NAT-2 and CYP2E1 genes and the activity of their enzymatic gene products, involved in the disposition of many xenobiotics, in a group of nonagenarians and in much younger controls. PATIENTS: the three genotypes were determined in 41 nonagenarians (10 males, mean age 92.2 years, range 90-98) free of known malignancies or neurodegenerative diseases. The control groups comprised 217 healthy volunteers (128 males, mean age 36.3 years; SD, 12.7) for the CYP2D6 and NAT2 genotypes and 137 (116 males, mean age 32 years; SD, 18.8) for the CYP2E1 genotype. METHODS: after extraction of DNA from white blood cells, polymerase chain reaction and restriction fragment polymorphism methods were used to identify the allelic variants of the three genotypes. RESULTS: we found no qualitative or quantitative difference in the mutations underlying the three genetic polymorphisms studied, nor in the expected enzymatic phenotypes. Instead, a close parallelism exists between advanced age and younger groups. CONCLUSION: longevity does not seem to be related to any special configuration of these three polymorphic traits. Comparisons with younger controls may be adequate when studying the distribution of these polymorphisms in diseases affecting old people. No genetically determined differences in the activation of drugs metabolized by these enzymes are to be expected in very old people.

Aged↗
PubMed1984

Genetic polymorphisms of Pe and Po salivary proteins with probable linkage of their genes to the salivary protein gene complex (SPC).

Two new genetic polymorphisms (Pe and Po) are found in human parotid saliva. Each polymorphism is determined by the autosomal inheritance of one expressed (dominant) and one unexpressed (recessive) allele. Autosomal inheritance is supported by studies of 63 families including 264 children for Pe and 57 families including 242 children for Po. For randomly collected salivas, gene frequencies in 317 whites are Pe+ = 0.76 and Pe- = 0.24; in 408 whites, Po+ = 0.75 and Po- = 0.25; in 51 blacks, Pe+ = 0.76 and Pe- = 0.24; and in 59 blacks, Po+ = 0.77 and Po- = 0.23. Both Pe and Po proteins react immunologically with polyclonal antisera prepared to proline-rich proteins PRPs. The Pe protein has an isoelectric point of approximately pH 6.1-6.3, and the Po protein has an isoelectric point greater than pH 8.0. In randomly collected salivas, the Pe and Po proteins are associated with other known salivary PRPs. The Pe protein is most strongly associated with the CON 1 and Ps proteins, is less strongly associated with the Pr and Pa proteins, and is not significantly associated with the PmF, PmS, PIF, Db, Con 2, or Gl proteins. If it is assumed that the strength of these associations (presumed linkage disequilibrium) may be related in part to map distance, then these data roughly fit the linear order of PRP genes as previously determined from recombination data derived from family linkage studies. The Po protein is associated with the PmS protein. There is evidence for probable linkage of Pe and Po to the SPC (salivary protein gene complex): Pe to Pa (nine families, lod score at theta = 0 is 2.67) and Po to CON 2 (three families, lod score at theta = 0 is 2.35).

Electrophoresis, Polyacrylamide Gel↗
PubMed1998

Genetic polymorphisms in human liver phenol sulfotransferases involved in the bioactivation of N-hydroxy derivatives of carcinogenic arylamines and heterocyclic amines.

Three related forms of phenol sulfotransferase (PSULT), thermostable ST1A2 (SULT1A2hum) and ST1A3 (SULT1A1hum) and a thermolabile TL-PST (SULT1A3hum), are known to exist in human livers. Thermostable forms, whose activities are polymorphically distributed, have been shown to mediate the bioactivation of carcinogenic N-hydroxy arylamines and heterocyclic amines. To clarify the nature of the sulfation polymorphism, the study compared the expressed levels of ST1A2, ST1A3 and TL-PST mRNAs in human livers by the method of reverse-transcriptase polymerase chain reaction (RT-PCR), utilizing HindIII, BamHI and SnaBI sites which were unique to the above PSULT cDNAs, respectively. Of the PCR products derived from human liver (n = 26), 43-89, < 1-29 and < 1-21% showed the restriction pattern characteristic for ST1A3, ST1A2 and TL-PST cDNAs, respectively, thus indicating that ST1A3 mRNA is the major transcript. Hepatic p-nitrophenol and dopamine sulfation rates ranged from 440-2670 and < 5-460 pmol/min per mg protein in the 26 individuals, respectively. The observed differences in the ST1A3 and TL-PST mRNA levels were consistent with the differences in p-nitrophenol and dopamine sulfations. Relative levels of hepatic ST1A3 mRNA were non-normally distributed and correlated significantly with p-nitrophenol sulfation. In addition, variant forms of ST1A3 mRNA encoding Arg213His and Met223Val were detected in human livers. With regard to Arg213His, 28 individuals who had homozygous 213Arg alleles, 15 individuals who were heterozygotes and nine homozygous 213His individuals were found by a newly established genotyping method among 52 human liver samples. Frequency of 223Val allele was apparently lower than that of 213His allele, as no homozygous 223Val individual and only three individuals who were heterozygotes (223Met/Val) were observed among 52 individuals. These results suggest that regulation of p-nitrophenol sulfation occurs at the level of gene transcription of ST1A3 which is the major transcript of the three PSULT mRNAs and that a polygenic basis for the apparent genetic polymorphism of sulfation was likely because of the existence of ST1A3 variants.

Amines↗
PubMed1986

Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a prototype of genetic polymorphism in oxidative drug metabolism. Purification and characterization of two similar forms involved in the reaction.

Two forms of cytochrome P-450 (P-450), designated P-450MP-1 and P-450MP-2, were purified to electrophoretic homogeneity from human liver microsomes on the basis of mephenytoin 4-hydroxylase activity. Purified P-450MP-1 and P-450MP-2 contained 12-17 nmol of P-450/mg of protein and had apparent monomeric molecular weights of 48,000 and 50,000, respectively. P-450MP-1 and P-450MP-2 were found to be very similar proteins as judged by chromatographic behavior on n-octylamino-Sepharose 4B, hydroxylapatite, and DEAE- and CM-cellulose columns, spectral properties, amino acid composition, peptide mapping, double immunodiffusion analysis, immunoinhibition, and N-terminal amino acid sequences. In vitro translation of liver RNA yielded polypeptides migrating with P-450MP-1 or P-450MP-2, depending upon which form was in each sample, indicating that the two P-450s are translated from different mRNAs. When reconsituted with NADPH-cytochrome-P-450 reductase and L-alpha-dilauroyl-sn-glyceryo-3-phosphocholine, P-450MP-1 and P-450MP-2 gave apparently higher turnover numbers for mephenytoin 4-hydroxylation than did the P-450 in the microsomes. The addition of purified rat or human cytochrome b5 to the reconstituted system caused a significant increase in the hydroxylation activity; the maximum stimulation was obtained when the molar ratio of cytochrome b5 to P-450 was 3-fold. Rabbit anti-human cytochrome b5 inhibited NADH-cytochrome-c reductase and S-mephenytoin 4-hydroxylase activities in human liver microsomes. In the presence of cytochrome b5, the Km value for S-mephenytoin was 1.25 mM with all five purified cytochrome P-450s preparations, and Vmax values were 0.8-1.25 nmol of 4-hydroxy product formed per min/nmol of P-450. P-450MP is a relatively selective P-450 form that metabolizes substituted hydantoins well. Reactions catalyzed by purified P-450MP-1 and P-450MP-2 preparations and inhibited by anti-P-450MP in human liver microsomes include S-mephenytoin 4-hydroxylation, S-nirvanol 4-hydroxylation, S-mephenytoin N-demethylation, and diphenylhydantoin 4-hydroxylation. Thus, at least two very similar forms of human P-450 are involved in S-mephenytoin 4-hydroxylation, an activity which shows genetic polymorphism.

Amino Acid Sequence↗
PubMed2006

[Genetic polymorphism of gluthation-S transferases and N-acetyl transferases 2 and nasopharyngeal carcinoma: the Tunisia experience].

Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes, which code for enzymes involved in detoxification. This genetic variability seems to be associated with the individual's susceptibility to certain cancers, including nasopharyngeal carcinoma. In this study, we have investigated the genotypic frequencies of DNA polymorphisms of two detoxification's genes: the gluthatione-S-transferase (GST) and the N-acetyl transferase 2 (NAT2). The study has included 45 patients with nasopharyngeal carcinoma compared to 100 healthy Tunisian controls. The presence of the GSTM1 null and GSTT1 null polymorphism was screened by using a multiplex PCR procedure. A PCR-RFLP method was used to detect polymorphism for the most common alleles of the NAT2 gene. Allelic frequencies between the two groups were compared using a chi2 test and odds ratio with 95% confidence intervals were calculated. The results indicate that the genotypic frequency of GSTM10/0 between controls and patients was significantly different. This genotype confers an increased risk of nasopharyngeal carcinoma (Odds Ratio = 2.12, [0.64-4.7]). However, genotypic frequencies of NAT2*6/NAT2*6 were significantly higher in the group of nasopharyngeal carcinoma patients. The calculated Odds Ratio showed an association between this genotype and nasopharyngeal carcinoma. In conclusion, the increase of nasopharyngeal carcinoma risk in Tunisia seems to be associated with GSTM10/0 and NAT2*6/6 genotype.

Arylamine N-Acetyltransferase↗
PubMed2004

[Genetic polymorphisms of three STR loci on chromosome X and their forensic application in a Chinese Han population].

OBJECTIVE: To understand the allele structure and genetic polymorphism at three STR loci on chromosome X in Chinese Han population and make an evalution of their forensic application. METHODS: EDTA-blood samples were collected from the unrelated individuals in Chengdu, China. After being extracted with Chelex method, the DNA samples were amplified by PCR technique. The PCR products were analyzed by PAG electrophoresis and the approach of automated fluorescence detection. Hardy-Weinberg equilibrium of females was tested and every forensic interested value was calculated. RESULTS: The polymorphisms of all 3 STR loci were obtained from 100 unrelated females and 120 unrelated males from Chinese Han ethnic group. Chi-square tests on the genotype frequencies in females did not reveal deviations from Hardy-Weinberg equilibrium. CONCLUSION: The obtained data are beneficial to understanding the population genetics of the three STR loci in Chinese Han population. For forensic genetics, the obtained data can be used to calculate the probabilities dealing with the paternity test and the individual identification.

China↗
PubMed2004

Genetic polymorphisms of CYP2A13 and its relationship to nasopharyngeal carcinoma in the Cantonese population.

Nasopharyngeal carcinoma (NPC) is characterized by a high prevalence in Southern China, especially among Cantonese individuals of the Guangdong Province. Epidemiological studies have suggested that frequent exposure to high levels of nitrosamine from preserved foods such as salted fish could be a risk factor for NPC. Cytochrome P450 encompasses a family of enzymes that metabolize carcinogens and CYP2A13, a member of this family, is expressed predominantly in the respiratory tract with the highest levels in the nasal mucosa. In an effort to test whether a correlation exists between CYP2A13 genetic polymorphism and the risk of developing NPC, we sequenced all nine exons and the exon-intron junctions of the CYP2A13 gene in 45 NPC patients. We identified a total of 21 single nucleotide polymorphism (SNPs), including 7 novel SNPs. The most frequent functional variant allele was 74A-1757G-3375T-7233G with a haplotype frequency of 7.8% in the 45 NPC cases. In addition, a stop codon mutation was detected in one case. We then selected the 3 most frequent SNPs and one stop codon mutation to expand our study to a case-control analysis within the Cantonese population. A novel haplotype consisting 8 SNPs in introns, and four additional novel SNPs were identified; but no correlation between CYP2A13 genetic polymorphism and individual susceptibility to NPC was observed.

Journal Article↗
PubMed1995

The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins de I'nfarctus du Mycocarde.

We have investigated the interrelationships of plasma PAI-1 activity, the PAI-1 4G/5G polymorphism and risk of myocardial infarction (MI) in the ECTIM study, a case-control study of MI based in Belfast, Lille, Strasbourg and Toulouse. Mean PAI-1 levels in cases were similar across all centres but in controls, levels in the French centres were significantly higher. Only in Belfast were PAIl1 levels higher in cases (11.7 AU/ml) than controls (10.5 AU/ml). The PAI-1 4G allele frequency was similar in cases and controls (0.55 and 0.54). In all groups, 4G homozygotes had the highest mean plasma PAI-1 level (4G4G vs 5G5G; cases overall: 14.2 vs 12.1AU/ml; controls overall: 15.0 vs 12.6AU/ml), with the heterozygotes generally intermediate. The data from Belfast are consistent with the literature implicating PAI-1 level as an MI risk factor. In ECTIM, the PAI-1 4G/5G polymorphism is not a genetic risk factor for MI but is associated with PAI-1 activity. Thus homozygosity for the 4G allele may predispose to elevated PAI-1 and impaired fibrinolysis, perhaps requiring interaction with other genetic or environmental factors to influence MI risk.

Adult↗
PubMed1991

Genetic polymorphism of sorbitol dehydrogenase in the brown hare and the distribution of the variation in central Europe.

A genetic polymorphism of sorbitol dehydrogenase (SDH; EC 1.1.1.14) for two allozymes is demonstrated in the brown hare (Lepus europaeus) by means of horizontal starch gel electrophoresis. Segregation analysis was performed in a sample of four matings with 12 offspring and confirmed the genetic hypothesis: two alleles at an autosomal locus. The calculated gene frequencies in the brown hare breed studied are Sdha = 0.712 and Sdhb = 0.288. The distribution of the polymorphism in free-ranging brown hare populations from Austria, Czechoslovakia, Hungary, and Poland is described.

Alleles↗
PubMedDate not supplied

Genetic polymorphisms of cytokine genes and risk for trichloroethylene-induced severe generalized dermatitis: a case-control study.

Trichloroethylene (TCE)-induced severe generalized dermatitis (SGD) is considered to be a contact allergic disease and is dependent on a cell-mediated immune response. Little is known about its pathogenesis. Several lines of evidence suggest that tumour necrosis factor (TNF) and interleukin 4 (IL-4) are involved in the immunological and inflammatory reactions. To investigate the relation between polymorphisms of TNF and the IL-4 gene and the risk of TCE-induced SGD, a case-control study was conducted consisting of 111 patients diagnosed with SGD and 152 TCE-exposed workers without SGD. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of TNF-alpha (G-238A, G-308A), TNF-beta (intron 1) and IL-4 (C-590T). Logistic regression was applied to calculate the odds ratios (OR) and 95% confidence intervals. The results reveal that the frequency of TNF alpha-308 wild allele in cases was significantly higher than that in control subjects (p=0.049). Individuals with a heterozygous genotype of TNF alpha-308 were associated with the decreased risk of TCE-induced SGD relative to the homozygous genotype (OR=0.398, 95% CI=0.164-0.967). No significant differences in the allele and genotype frequencies could be demonstrated at any other polymorphic loci among both groups. The finding of a possible contribution of a TNF-alpha genetic polymorphism is a primary result because the pathogenesis of TCE-induced SGD is complex and likely to involve the interaction of a number of genes. A further study should be conducted to illustrate the influence of a link between certain relevant alleles in the assessment of genetic susceptibility

Adult↗
PubMed1999

[Genetic polymorphism at D3S1545 locus in Chengdu Han and Dali Bai populations in China].

The objective of this study was to understand the distribution of the genetic polymorphisms of STR locus D3S1545 in Chinese populations. EDTA-blood specimens were collected from 148 healthy unrelated Han individuals in Chengdu and 96 healthy unrelated Bai individuals in Dali. The DNA samples were extracted using Chelex method, and then they were amplified by PCR technique. PAGE horizontal electrophoresis was used for typing the PCR product. The results there were nine alleles at D3S1545 locus in Chengdu Han population and six alleles at D3S1545 locus in Dali Bai population. The allele frequencies of Chengdu Han population were D3S1545 * 8:0.0642; D3S1545 * 9:0.0034; D3S1545 * 10:0.0068; D3S1545 * 11:0.0203; D3S1545 * 12:0.1824; D3S1545 * 13:0.3075; D3S1545 * 14:0.3243; D3S1545 * 15:0.0844; D3S1545 * 16:0.0068; and 23 genotypes were observed. The allele frequencies of Dali Bai population were D3S1545 * 8:0.00781; D3S1545 * 11:0.0261; D3S1545 * 12:0.1719; D3S1545 * 13:0.3906; D3S1545 * 14:0.2448; D3S1545 * 15:0.0885; and 16 genotypes were observed. The results of test for Hardy-Weinberg equilibrium showed that the genotype distributions observed at the populations were correspondent with the expected. These findings suggest that the allele frequencies at D3S1545 locus in Chengdu Hans have not remarkable different from those in the Bai population of Dali. D3S1545 may be a useful marker for paternity test and personal identification of biological stain.

Alleles↗
PubMed2000

[Genetic polymorphism of 10 STR loci on chromosome 9 and its forensic application in Chinese population].

OBJECTIVE: To have a thorough knowledge of the genetic polymorphism of 10 short tandem repeats loci of chromosome 9 in Chinese population and its application in forensic science. METHODS: The 9 STR tetrameric loci and one trimeric tandem repeat locus were chosen from Genome Databank. Eighty-three EDTA-blood samples were collected from the unrelated family in Baiyin city, Gansu province. DNA was extracted by Chelex method and amplified by the polymerase chain reaction(PCR). The PCR products were analyzed by PAGE electrophoresis. RESULTS: The polymorphisms of all 10 STR loci have been obtained in Chinese Han population. The 10 STR loci follow the Mendel ns law. CONCLUSION: The data of all 10 STR loci is beneficial to understanding the population genetics of them in Chinese Han population.

Chromosomes, Human, Pair 9↗
PubMed2001

[Effect of complement 4 genetic polymorphism on complement activation during cardiopulmonary bypass in open heart surgery among children].

OBJECTIVE: To evaluate the relation between complement 4 genetic polymorphism and complement activation during extracorporeal circulation in open heart surgery among children. METHODS: One hundred and fifty-six children to undergo open heart surgery with cardiopulmonary bypass in Wuhan and surrounding areas were investigated. Blood samples were obtained before the operation to analyze the C4 phenotypes by crossed immunoelectrophoresis. Before the initiation of CPB, at the end of CPB, and 10 minutes after protamine infusion, arterial blood samples were drawn to test the C4a and C3a with radioimmunoassay and lung compliance was recorded. RESULTS: The frequencies of C4 genetic phenotypes AABB, AOBB, OOBB, AABO, and AAOO were 51.28%, 17.95%, 4.49%, and 19.80% respectively among the investigated children. At the end of CPB, The C4a levels remained almost the same, and C3a levels increased significantly. Ten minutes after the protamine infusion, significant increase was seen in the levels of both C4a and C3a, especially in the OOBB phenotype group followed by AOBB phenotype group. The lung compliance began to decrease by the end of CPB, most significantly in the OOBB phenotype group, followed by the AOBB group, along with the increase of C4a level. CONCLUSION: The complement system is activated by the alternative pathway during CPB and by the classic way during the formation of protamine-heparin complexes. The complement system is activated and the lung function is damaged the most seriously during CPB among the persons with OOBB phenotype. The frequency of OOBB phenotype is higher among Chinese than among Caucasians.

Cardiac Surgical Procedures↗
PubMed1997

Genetic polymorphism of monoamine oxidase B and susceptibility of Parkinson's disease.

BACKGROUND: Monoamine oxidase B (MAO-B) may play a role in the progression and cause of Parkinson's disease (PD), given consideration of the biochemistry and pathophysiology of the disease, and experiments on primates and humans. Assuming that the structural gene determines enzyme activity, an association study was undertaken to examine MAO-B genetic polymorphisms and look for the unique MAO-B gene alleles which occurred at a higher frequency in PD patients. METHODS: Sixty-five PD patients, diagnosed according to the criteria set by a Core Assessment Program for Intracerebral Transplantations Committee, and 108 healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral leukocytes by using a puregene kit. Polymerase chain reaction (PCR) was used to amplify the MAO-B genome. The PCR products were screened by restriction enzyme Hae III digestion and analyzed by single-stranded conformational polymorphism (SSCP). RESULTS: Two bands with different mobility shifts, defined as MAO-B allele 1 and allele 2, were observed in SSCP analysis. Neither genotypes nor allelic frequencies of MAO-B showed a significant difference between PD patients and controls in our study. CONCLUSIONS: Polymorphism of MAO-B genome was demonstrated in this study. It failed to show an association of a genetic marker with PD. However, this did not necessarily exclude the MAO-B locus from playing a role in causing PD because a polymorphism different from the one evaluated here may show some disease association.

Aged↗
PubMed2002

Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility.

Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.

Cytochrome P-450 CYP1A1↗
PubMed2006

Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma.

The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-1B (ADH1B, previously called ADH2), and ADH1C (previously called ADH3) affect the metabolism of alcohol. The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active ADH1B encoded by ADH1B*1/*1 increase the risk of esophageal squamous cell carcinoma in East Asian drinkers. This case-control study involved 96 Japanese men with oral and pharyngeal squamous cell carcinoma (hypopharyngeal cancer in 43 patients and oral/oropharyngeal cancer in 53) and 642 cancer-free Japanese men. The risk of the cancers overall and of hypopharyngeal cancer was increased 3.61- and 10.08-fold, respectively, by ALDH2*1/*2 among moderate-to-heavy drinkers (9+ units/week; one unit = 22 g of ethanol), but the risk of oral/oropharyngeal cancer was not significantly affected by the ALDH2 genotype. The results obtained with a simple alcohol flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping. Among moderate-to-heavy drinkers, men with the less-active ADH1B*1/*1 had a significantly higher risk of the cancers overall, of hypopharyngeal cancer, and of oral/oropharyngeal cancer (OR = 5.56, 7.21 and 4.24, respectively). In view of the linkage disequilibrium between ADH1B and ADH1C, the ADH1C genotype does not significantly affect cancer risk. The significant independent risk factors for oral and pharyngeal cancer overall among moderate-to-heavy drinkers were inactive ALDH2*1/*2, less-active ADH1B*1/*1, frequent drinking of strong alcohol beverages straight, smoking, and lower intake of green-yellow vegetables. Educating these risks for cancer of the upper aerodigestive tract could be a useful new strategic approach to the prevention of these cancers in Japanese.

Adult↗
PubMed2001

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer.

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical-associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (+/-3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15-6.67) as compared with the XRCC1(399) Arg/Gln and XRCC1(399) Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol-associated esophageal cancers.

Adult↗