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N Caporaso

Publications and source records attributed to N Caporaso.

At least 19 recordsLinked to original sources
PubMed1998

Alpha-glutathione transferases in HCV-related chronic hepatitis: a new predictive index of response to interferon therapy?

BACKGROUND/AIM: The aim of this study was to evaluate if plasma levels of alpha-glutathione-S-transferases (determined in basal conditions and monthly for 1 year during and 1 year after interferon therapy) could characterize patients who show only a primary response. METHODS: We studied 48 patients with biopsy-proven, hepatitis C virus ribonucleic acid positive chronic hepatitis treated with interferon: 18 were "Sustained Responders", 12 "Relapsers" and 18 "Non-Responders". RESULTS: Relapsers showed higher basal levels of alpha-glutathione-S-transferases, which remained higher than normal even when alanine aminotransferases normalized. No correlation was documented between alpha-glutathione-S-transferase levels and all other parameters examined (alanine aminotransferases, gamma-glutamyl-transpeptidase, viremia, and histological activity index). CONCLUSIONS: These findings suggest that alpha-glutathione-S-transferase levels may be considered a predictive index of response to interferon therapy in chronic hepatitis C patients.

Adult↗
PubMed1998

Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene.

This study evaluated whether there are genetic subgroups of depressed individuals who are more or less predisposed to engage in self-medication smoking practices. Smokers (N = 231) completed self-report questionnaires of depression and smoking practices and were genotyped for the dopamine D4 receptor (DRD4) gene. A significant interaction (DRD4 Genotype x Depression) was found for stimulation smoking and negative-affect reduction smoking. Specifically, these smoking practices were significantly heightened in depressed smokers homozygous for the short alleles of DRD4 but not in those heterozygous or homozygous for the long alleles of DRD4. These preliminary results suggest that the rewarding effects of smoking and the beneficial effects of nicotine replacement therapy for depressed smokers may depend, in part, on genetic factors involved in dopamine transmission.

Adult↗
PubMed1998

Spread of hepatitis C virus infection within families. Investigators of an Italian Multicenter Group.

In 1995, the intrafamilial spread of hepatitis C virus (HCV) was evaluated among 1379 household contacts of 585 HCV antibody-positive HCV RNA-positive subjects (index cases) in Italy. All index cases were patients with histologically proven chronic liver disease. The presence of antibodies to HCV (anti-HCV) was assessed by third-generation enzyme-linked immunosorbent assay (ELISA); the polymerase chain reaction (PCR) was used to test for HCV RNA. The overall anti-HCV prevalence among household contacts of index cases was 7.3% (101/1379); it was 15.6% in spouses and 3.2% in other relatives (P < 0.05; odds ratio (OR), 6.5; 95% confidence interval (CI), 3.5-8.6). Spouses married to index cases for longer than 20 years had a significantly higher anti-HCV prevalence than those married 20 years or less (19.8% vs 8.0%; P< 0.05; OR, 2.8; 95% CI, 1.5-5.3). Parenteral risk factors were more likely to be reported in anti-HCV positive than in anti-HCV negative household contacts. After adjustment for confounders by multiple logistic regression analysis, age greater than 4 5 years (OR, 3.1; 95% CI, 1.6-5.3) and any parenteral exposure (OR, 3.7; 95% CI, 1.7-8.1), were the only independent predictors of the likelihood of anti-HCV positivity among household contacts. Spouses versus other relatives and length of marriage were both no longer associated. These findings suggest that sexual transmission does not seem to play a role in the intrafamilial spread of HCV infection.

Adult↗
PubMed1998

Chronic hepatitis C long-term responders to human leukocyte interferon-alpha therapy: persistence of a sustained biochemical and virological response during 5 years of surveillance.

OBJECTIVES: To define the biochemical and virological course and IgM response to HCV-core protein in long-term responders (LTRs) during a long surveillance (5 years). DESIGN: From 1989 to 1991, 98 patients (pts) with biopsy-proven chronic hepatitis C were enrolled into this study. These pts underwent human leukocyte interferon-alpha (LE-IFN alpha) therapy at the prolonged schedule (3 MU thrice weekly for 1 year). METHODS: Serum alanine-aminotransferases (ALTs) were assessed monthly during and until 1 year after treatment, then every 3 months during the observation period. Qualitative and quantitative HCV RNA and HCV IgM were measured in all pts on baseline samples and in LTRs also after treatment and every following year. RESULTS: Based on serum ALT course, the pts were defined as: LTRs (14 pts), if their serum ALT levels returned to the normal range during therapy and remained so for at least 1 year afterwards; responders with relapse (RRs, 20 pts), if their serum ALT levels returned to the normal range during therapy but increased after ending treatment; and non-responders (NRs, 64 pts), if their serum ALT levels remained abnormal throughout therapy. No significant differences were seen regarding IgM anti-HCV positivity and serum ALT levels among the three groups. LTRs (12 HCV-RNA negative and two HCV-RNA positive at the end of treatment) maintained their virological status and not one of them experienced an elevation of serum ALT levels throughout the surveillance. CONCLUSION: Patients affected by chronic hepatitis C and treated with interferon, but who did not experience a biochemical or virological relapse within the first year of follow-up would not relapse later on; thus, we are able to conclude that these subjects made a complete recovery.

Adult↗
PubMed1998

The role of the serotonin transporter gene in cigarette smoking.

Data from twin studies have suggested that cigarette smoking has a significant heritable component. The serotonin transporter gene (5-HTT) is a plausible candidate gene for smoking predisposition because of its association with psychological traits relevant to smoking behavior. The present investigation evaluated the associations of smoking practices and smoking cessation with a common polymorphism in the upstream regulatory region of 5-HTT that is manifested as either an inserted (long) variant or a deleted (short) variant. The short variant of the polymorphism is associated with reduced transcription of the gene promoter and diminished uptake. A case-control study design (268 smokers and 230 controls) was used to evaluate the associations of 5-HTT genotype with smoking status. Case series analysis of smokers was used to evaluate the role of 5-HTT in age at smoking initiation, previous quitting history, current smoking rate, and 12-month quit rate following a minimal-contact smoking cessation program. There were no significant differences in the distribution of 5-HTT genotypes in smokers as compared with nonsmokers in either Caucasians or African Americans, nor was the 5-HTT genotype associated with the smoking outcome variables. However, the results did reveal significant racial differences in the distribution of 5-HTT genotypes: Caucasians were significantly more likely to carry the short variant of the 5-HTT gene than were African Americans (P = 0.005). These findings suggest that the 5-HTT gene may not play a significant role in cigarette smoking practices.

Adult↗
PubMed1997

Heredity and prostate cancer: a study of World War II veteran twins.

BACKGROUND: Increased risk of prostate cancer among men with a family history of the disease has been observed in several epidemiological studies, and family studies have identified hereditary prostate cancer characterized by early onset and autosomal dominant inheritance. METHODS: In this study, we examine prostate cancer heritability among twins in the NAS-NRC Twin Registry, with cases ascertained from a number of sources: recent telephone interviews, Medicare and Department of Veterans Affairs hospitalizations, previous mail questionnaires, and death certificates. A total of 1,009 prostate cancer cases were identified among the cohort of 31,848 veteran twins born in the years 1917-1927. RESULTS: Probandwise concordance for prostate cancer was substantially higher among monozygous twin pairs, 27.1%, than among dizygous twin pairs, 7.1% (P < 0.001). CONCLUSIONS: These data suggest that genetic influences account for approximately 57%, and environmental influences for 43%, of the variability in twin liability for prostate cancer.

Aged↗
PubMed1997

Frequency of the variant allele CYP2D6(C) among North American Caucasian lung cancer patients and controls.

Previous reports of the association between the debrisoquine polymorphism and lung cancer risk are conflicting. Following the report of an association between lung cancer risk and the variant allele CYP2D6(C), we examined the presence of this allele in 98 incident Caucasian lung cancer patients and 110 age, race, and sex matched hospital controls from a case-control study conducted at the National Naval Medical Center in Bethesda, MD. Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8 h urine collected. Genomic DNA was genotyped by a specific polymerase chain reaction amplification and subsequent restriction enzyme digestion, and Southern analysis. Twenty subjects were heterozygous for the CYP2D6(C) allele but none were homozygous for this allele. There was no significant difference in frequency of CYP2D6(C) between lung cancer patients and controls (5.61% and 4.09%, respectively), and there was no significant heterogeneity among cases by histologic type of lung cancer (P = 0.08). However, 7 of 11 cases (64%) with the CYP2D6(C) allele had small cell lung cancer, and none had squamous cell carcinoma. Carrying the CYP2D6(C) allele did not impair debrisoquine metabolism to the same degree as the known inactivating mutations, CYP2D6(A) and CYP2D6(B), or deletion of CYP2D6. Thus, the CYP2D6(C) allele does not encode a completely inactivating mutation, and the suggestion of a role for this variant allele in the risk for specific histologic types of lung cancer justifies further investigation.

Alleles↗
PubMed1997

Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: issues involved in incorporating putative genetic susceptibility markers into epidemiological studies.

PURPOSE: Heterocyclic amines (HCAs), which are found mainly in well-cooked meat, require metabolic activation to function as mutagens and animal carcinogens. Enzymes such as cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) perform this task and are subject to interindividual variation. The source of this variation may be genetic, as in the case of NAT2, or both genetic and environmental as with CYP1A2. The present study examined the effect of HCAs on the NAT2 and CYP1A2 phenotypes in 33 males and 33 females. METHODS: The subjects consumed a low HCA-containing diet for 1 week followed by a high HCA diet for the subsequent week. The subjects were phenotyped for CYP1A2 and NAT2 at the time of entry into the study (free-living), 1 week later (end of low-HCA or low-induction diet) and 2 weeks later (end of high-HCA or high-induction diet). RESULTS: Consistent with genetic sources of variability, NAT2 showed little effect of a high-HCA diet and exhibited high intraindividual correlation. CYP1A2, in contrast, was induced by a high-HCA diet and exhibited a more modest intraindividual correlation. CONCLUSIONS: Incorporating putative genetic susceptibility makers in population studies requires consideration of issues of induction and inhibition of metabolizing enzymes, and effects of covariates.

Amines↗
PubMed1997

Incorporating biomarkers of exposure and genetic susceptibility into smoking cessation treatment: effects on smoking-related cognitions, emotions, and behavior change.

In this article the authors report on the short-term impact of incorporating biomarker feedback about exposure and genetic susceptibility into minimal-contact quit-smoking counseling (QSC). Four hundred and twenty-seven smokers were randomized to 1 of 3 treatments: (a) QSC, (b) QSC + exposure biomarker feedback (EBF) about carbon monoxide in exhaled breath, or (b) QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer (SBF). We observed significant immediate positive effects of SBF, compared with EBF and QSC on perceived risk, perceived quitting benefits, and fear arousal. However, at the 2-month follow-up, there were no group differences in quit rates. SBF did lead to significant reductions in the number of cigarettes smoked for smokers who were in the preparation stage. Smokers in the EBF and QSC conditions showed reductions in depressive symptoms by 2 months, but smokers in the SBF condition did not. In the context of QSC, genetic feedback may heighten vulnerability and possibly promote distress, but may not immediately enhance quitting in most smokers.

Adolescent↗
PubMed1997

Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer.

Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over-expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer.

Aged↗
PubMed1997

Family history of cancer and risk of lung cancer in lifetime non-smokers and long-term ex-smokers.

BACKGROUND: Genetic factors appear to play a role in the aetiology of lung cancer. METHODS: To examine the association between family history of cancer (all types) and risk of lung cancer among non-smokers, we conducted a case-control study. Cases (n = 618) were identified through the Missouri Cancer Registry for the period 1986 through 1991, and included 432 lifetime non-smokers and 186 ex-smokers who had stopped at least 15 years prior to diagnosis or had smoked for less than one pack-year. Controls (n = 1402) were selected through drivers licence and Medicare files. RESULTS: The risk of lung cancer increased directly in relation to the number of family members affected with cancer. The odds ratio (OR) associated with five or more first-degree relatives with cancer was 2.7 (95% confidence interval [CI] 1.2-6.1), with a significant linear trend in risk according to the number of relatives affected (P = 0.03). Increased lung cancer risk was associated with two or more affected siblings (OR = 1.4; 95% CI: 1.0-1.9) and with two or more affected offspring (OR = 3.2: 95% CI: 1.3-8.1). Risk was slightly elevated for family history of lung cancer (OR = 1.3; 95% CI: 1.0-1.8). CONCLUSIONS: Our study identified a slight increase in risk of lung cancer in relation to five or more relatives with cancer. Preventive implications of this increased risk are unclear because the attributable fraction is low in comparison to a variety of other factors.

Adult↗
PubMed1997

Sample collection, processing and storage.

We review issues related to the inclusion of biospecimens in epidemiological studies. Technical advances and the revolution in molecular biology have rendered the use of biomarkers increasingly feasible in epidemiological investigations, however the cost and complexity require interdisciplinary expertise and careful attention to methodological detail in order to ensure validity. The widespread banking of biospecimens for long-term (cohort) studies requires special attention to be paid to these issues. Blood, urine and tumour tissue are in common use in medicine and at least some aspects of sample handling derives directly from this clinical experience, although special considerations apply in the epidemiological setting. An increasingly broad array of biospecimen types have been studied, including exhaled air, nail clippings, buccal cells, saliva, semen, faeces and breast milk. Relevant issues in the processing, storage, shipping, timing of collection and safety procedures are examined in terms of their potential to distort results. The role of carefully developed quality control protocols is emphasized. In order to take full advantage of the opportunities afforded by the use of biomarkers in epidemiological studies, careful attention to biospecimen processing, the stability of the biomarker and the precautions to be taken during transportation and storage of samples is necessary.

Biomarkers, Tumor↗
PubMed1997

Issues involving biomarkers in the study of the genetics of human cancer.

The investigation of hereditary factors in human cancer was suggested from kindreds that exhibited aggregations of cancer consistent with Mendelian inheritance. A subset of cancer that exhibits strong familial tendencies is due to single genes that 'cause' cancer; more commonly, hereditary factors may influence tumorigenesis in a stepwise probabilistic rather than deterministic manner through a variety of mechanisms, e.g. influencing the disposition of carcinogens. The roles of both common susceptibility genes and rare 'familial' cancer genes are receiving increasing attention in the general population. Population-based studies designed to examine more common genetic variants differ from linkage-based studies. Candidate susceptibility genes may be studied by phenotype or genotype approaches, and the relative advantages and disadvantages of each approach are considered. The issue of gene-environment interaction, implicit in the concept of susceptibility genes, is considered. The influence of genetic factors on individual and attributable risk is addressed.

Biomarkers, Tumor↗
PubMed1995

Cancer genes: single and susceptibility: exposing the difference.

'Single' genes, necessary and sufficient to cause cancer, are contrasted with 'susceptibility' genes that are neither, but may act in the presence of specific environmental exposures to alter the chances of cancer in the host. The former are rare, are of high absolute and relative risks, have minimal dependence on exposures and therefore have low population attributable risks. A small number of such genes are well established in the literature and typically exhibit familial aggregations of disease that serve as a starting point for genetic studies. 'Susceptibility' genes, as typified by the pharmacogenetic model, are common, have low relative and absolute risk, are strongly dependent upon exposure, and may have potentially high population attributable risks. Mechanistic and epidemiologic data are suggestive but currently fall short of confirmation for these associations. Familial aggregation is not a prominent feature and epidemiological study designs with careful exposure assessment is the investigative method of choice. Both approaches require interdisciplinary expertise and benefit from advances in molecular biology.

Environmental Exposure↗