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M de Andrade

Publications and source records attributed to M de Andrade.

At least 37 records · Page 2Linked to original sources
PubMed2000

Gender difference in smoking effect on chromosome sensitivity to gamma radiation in a healthy population.

In the general population, there is variation in radiosensitivity associated with cancer risk. However, data on the role of epigenetic factors in the variation of radiosensitivity are scarce. Thus we investigated the effects of smoking and age on the radiosensitivity of human lymphocytes by measuring the frequency of chromosome aberrations after in vitro exposure to gamma rays in peripheral lymphocytes from 441 healthy subjects (18-95 years old). We analyzed the frequency of both spontaneous (baseline) and in vitro gamma-ray-induced (1.5 Gy) chromatid breaks in 50 well-spread metaphases per subject. The overall mean frequencies of spontaneous and induced breaks were 0.02 and 0.45 per cell, respectively. The mean frequency of induced breaks was significantly higher in men than in women (P = 0.03) but did not differ by age or ethnicity. Donors who had ever smoked showed a small but significantly increased frequency of induced breaks (mean = 0.47) compared to nonsmokers (mean = 0.41; P = 0.005). Further stratification and multivariate analyses revealed that the smoking effect was more pronounced in men than in women. These findings support a smoking effect on radiosensitivity in a healthy population, particularly in men. Therefore, when evaluating the association between radiosensitivity and susceptibility to smoking-related cancers, the effect of smoking should be taken into account.

Adult↗
PubMed2000

Statistical models for analysis of cytogenetic biomarkers.

BACKGROUND: Bleomycin-induced chromosomal breaks (CB) and sister chromatid exchange (SCE) in peripheral blood lymphocytes have been shown to be sensitive cytological markers for susceptibility to DNA damage in patients with various types of cancer and in healthy controls. Factors such as age, sex, smoking, and alcohol consumption could affect the values of some of these biomarkers and should be considered as covariates when analyzing cytogenetic biomarkers because these factors can affect the frequency of CB and SCE. METHODS: We propose a statistical method using negative binomial (NB) distribution to evaluate the numbers of CB and SCE. In order to determine the best model to represent the frequency of CB and SCE, we compared the NB model with the widely used Poisson model and log-transformed normal model by using generalized linear models. To demonstrate the better fit of the NB model, we analyzed three different data sets from studies conducted at The University of Texas M.D. Anderson Cancer Center. The first set was a case-control study of lung cancer in a population of African Americans and Mexican Americans (286 cases and 156 controls), the second set consisted of 311 head and neck cancer patients, and the third set consisted of 105 Hodgkin's disease patients. RESULTS: For CB; the estimates of the variability for Hodgkin's disease, head and neck, and lung cancers were 487.24, 502.82, and 520.15, respectively. For SCE, the estimates of the variability for Hodgkin's disease was 9777.01. For CB, the dispersion estimates under the three models (Poisson, NB, and Normal) for Hodgkin's disease, head and neck, and lung cancers were: 12.30, 1.20, 0.85; 8.94, 1.05, 0.22; and 10.10, 1.05, 0.25, respectively. For SCE (Hodgkin's disease only), the dispersion estimates under the three models (Poisson, NB, and Normal) were 30.91, 1.11, 0.10, respectively. CONCLUSIONS: Our results demonstrate that the NB model provides a better interpretation and fit for the frequency of CB and SCE in different cancer types. Therefore, we recommend it as a model for the analysis of cytogenetic biomarkers.

Biomarkers↗
PubMed2000

Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk.

Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. One proposed mechanism for their protective action is through down-regulation of cytochrome P-450 biotransformation enzyme levels and induction of phase II detoxifying enzymes. Because ITCs also serve as a substrate for GSTs, we evaluated dietary intake of ITCs and GSTM1 and GSTT1 genotype information in a lung cancer case-control study. There were 503 newly diagnosed lung cancer cases (264 men and 239 women) identified from The University of Texas M. D. Anderson Cancer Center and 465 controls (252 men and 213 women) recruited from enrollees in a local managed care organization. Subjects had an in-person interview including a semiquantitative food frequency questionnaire, and blood samples were obtained for genotyping. Cases reported significantly lower ITC intake per day compared with controls (P = 0.009). There was no main effect associated with the GSTM1 null genotype [odds ratio (OR) = 1.09]. However, there was a statistically significant OR of 1.41 associated with the GSTT1 null genotype. On stratified analysis, low ITC intake and the GSTM1 null genotype were associated with increased lung cancer risk in current smokers, with an OR of 2.22 [confidence interval (CI) = 1.20-4.10). For current smokers with the GSTT1 null genotype, the OR with low ITC intake was 3.19 (CI = 1.54-6.62). The comparable OR in the presence of both null genotypes was 5.45 (CI = 1.72-17.22). These effects were not demonstrable for former smokers by GSTM1 genotype, although the risk for low ITC intake and GSTT1 null genotype was 1.79 (CI = 0.95-3.37). Thus, current smokers who are homozygous null for the GST null genotype and who consume less carcinogenic blocking compounds are at higher lung cancer risk. Some of the inconsistencies reported in the role of GST genotypes in lung cancer risk could be due to unexpected confounding from dietary factors.

Aged↗
PubMed1999

Methods to estimate genetic components of variance for quantitative traits in family studies.

The aim of this paper was to compare several methods of estimating the genetic components of a quantitative trait in familial data. The Expectation and Maximization (E-M) algorithm, the Newton-Raphson method, and the scoring method were compared for estimating polygenic and environmental effects on nuclear families. We also compared scoring and quasilikelihood (QL) methods when a linked genetic marker was available to estimate effects from a major gene. Generally, all procedures performed similarly in estimating polygenic and environmental variance components. The E-M algorithm yielded more precise estimators when heritability was low. The scoring method was much faster than the other methods and yielded slightly more precise estimates of mean effects but slightly less precise estimates of the variance components. Estimates of major gene effects were not affected by the number of alleles at the trait locus. For these relatively large sample sizes, QL and scoring had similar precision, but QL took 32 times longer than scoring. Finally, we compared the results of applying these methods to data from the Bogalusa Heart Study. Results showed larger imprecision when the QL method was applied, consistent with earlier studies that showed decreased precision of quasilikelihood compared with maximum likelihood in moderately small sample sizes.

Algorithms↗
PubMed1999

Assessing linkage of monoamine oxidase B in a genome-wide scan using a univariate variance components approach.

We report results when one alcoholism related quantitative trait, monoamine oxidase B (MAOB), is analyzed by the variance components approach for linkage [Amos, 1994; Amos et al., 1996] using the Collaborative Study on the Genetics of Alcoholism data set provided for the Genetic Analysis Workshop 11. We used two different covariate models, one with age at interview, sex, ethnicity, and smoking status and the other with age at interview, sex, and ethnicity. The univariate analysis showed 24 markers on four different chromosomes (1, 4, 9, and 12) to have evidence for linkage with the quantitative trait (single-point and multipoint linkage). However, when outliers for MAOB were removed, the significant evidence for linkage disappeared.

Chromosomes, Human, Pair 1↗
PubMed1999

Genome scans for genetic predisposition to alcoholism by use of transmission disequilibrium test analyses.

We report the results of the analysis of three measures of alcoholism and six associated symptoms using transmission disequilibrium (TDT) analysis on data from the Collaborative Study on the Genetics of Alcoholism data set. Implementation of identity-by-state (IBS) routines for error checking revealed 10 reported full siblings that were rejected as a full sibling to all of their purported full siblings with p < 0.05. TDT analysis revealed two loci with significant transmission disequilibrium (p < 0.001) on chromosomes 1 and 7. Analysis by parental origin found alleles at three loci displaying significant disequilibrium in the transmission of the paternal alleles for at least three of the nine tested traits. These loci are on chromosomes 6, 9, and 13. Analyses of Caucasian families alone and the use of a single affected individual from each family also yielded significant results for the loci on chromosomes 6, 9, and 13.

Alcoholism↗
PubMed1999

A genome-wide search for susceptibility genes linked to alcohol dependence.

We performed two-point linkage analysis during a genome-wide search for susceptibility genes that predispose to alcohol dependence with the Collaborative Study on the Genetics on Alcoholism (COGA) data made available for the Genetic Analysis Workshop 11 (GAW11). For chromosomes 1 and 4 our findings supported results reported by Reich et al. [1998] based on the same data. We found similarity between our findings in regions on chromosomes 8 and 10 and reported results for schizophrenia linkage studies. Differences between our results with COGA data and those obtained by Reich et al. [1998] are due to our use of a lod score method versus their use of the affected relative pair (sib pair) method.

Alcoholism↗
PubMed1999

Alopecia areata in families: association with the HLA locus.

Alopecia areata (AA) is a T cell mediated disease directed against hair follicles that results in bald patches. It can range in severity from patchy (AA), to total scalp hair loss (alopecia totalis; AT) or body hair loss (alopecia universalis; AU). We have previously shown that HLA-DR4 and DR11 as well as HLA-DQ*03 alleles are increased in unrelated AA patients compared with controls. To study whether class II HLA alleles are linked to AA, we investigated 81 extended families that included 192 AA patients, including 89 with AT or AU. We also performed the transmission disequilibrium test (TDT) in 143 nuclear families. Results showed an association between alleles of HLA-DQB (p = 0.014) and HLA-DR (p = 0.010). We also performed linkage analysis in 75 families whose members' genomic DNA were available for HLA typing. Results from this analysis support linkage between AA and class II loci with a maximal LOD score of 2.42 to HLA-DQB at 5% recombination, and with a maximal LOD score of 2.34 to HLA-DR at 0% recombination. There was an increased incidence of atopic dermatitis and autoimmune thyroiditis in families. AA appears to be a class II HLA restricted organ specific immune response to the hair follicle.

Alleles↗
PubMed1999

Increased chromosomal instability in peripheral lymphocytes and risk of human gliomas.

Brain tumors exhibit considerable chromosome instability (CIN), suggesting that genetic susceptibility may contribute to brain tumorigenesis. To test this hypothesis, in this pilot study, we examined for CIN in short-term lymphocyte cultures from 25 adult glioma patients and 28 age-, sex- and ethnicity-matched healthy controls (all Caucasian). We evaluated CIN by a multicolor fluorescence in situ hybridization assay using two probes: a classic satellite probe for a large heterochromatin breakage-prone region of chromosome 1 and an alpha satellite probe for a smaller region adjacent to the heterochromatin probe. Our results showed a significant increase in the mean number of spontaneous breaks per 1000 cells in glioma patients (mean +/- SD, 2.4+/-0.8) compared with controls (1.4+/-0.9; P < 0.001). By using the median number of breaks per 1000 cells in the controls as the cutoff value, we observed a crude odds ratio (OR) of 8.5 [95% confidence interval (CI) = 2.05-34.9, P < 0.001] for spontaneous breaks and brain tumor risk. After adjustment for age, sex and smoking status, the adjusted OR was 15.3 (95% CI, 2.71-87.8). A significant increase in cells with chromosome 1 aneuploidy (in the form of hyperdiploidy) (P < 0.001) was also observed in the glioma cases, with an adjusted OR of 6.6 (95% CI = 1.5-30, P < 0.05). These findings suggest that CIN can be detected in the peripheral blood lymphocytes of brain tumor patients and may be a marker for identifying individuals at risk.

Aneuploidy↗
PubMed1998

Segregation analysis of idiopathic talipes equinovarus in a Texan population.

"Idiopathic" talipes equinovarus (ITEV) is a nonsyndromal congenital anomaly of one or both feet. Casting and surgery are often necessary to obtain correct foot alignment. In spite of treatment, residual deformities of the feet occur and calf muscles may be hypoplastic. The cause of ITEV is unknown but genetic factors have been postulated. Complex segregation analysis was performed on 173 ITEV families including 93 Caucasian and 48 Hispanic families. The recessive mixed model was the best fitting model and no differences were found based on ethnicity. These results confirm previous studies suggesting that there is a genetic component to the development of ITEV.

Clubfoot↗
PubMed1998

Segregation analysis of squamous cell carcinoma of the head and neck: evidence for a major gene determining risk.

We and others have shown that a family history of squamous cell carcinoma of the head and neck (SCCHN) is a risk factor for this disease. We performed a segregation analysis on a dataset comprised of 1429 first-degree relatives of 242 unselected cases of SCCHN and 934 first-degree relatives of 156 spouse controls. Using the SAGE software, we demonstrated that a Mendelian model was favored and a model postulating a purely environmental cause of SCCHN was rejected. The model suggests that 18% of the population who smoke and drink are susceptible. The lifetime risk for non-smokers and non-drinkers who are heterozygotes for the susceptible allele is close to zero, but for those heterozygotes who smoke and drink the risk is 14% by age 70. These findings suggest that specific genetic factors account for a significant fraction of the risk of SCCHN associated with a family history of SCCHN.

Alcohol Drinking↗
PubMed1998

Genetic polymorphisms in glutathione S-transferase mu and theta, N-acetyltransferase, and CYP1A1 and risk of gliomas.

The role of genetic polymorphisms in modulating susceptibility to carcinogenic exposures has been well explored for tobacco-related neoplasms but not for other neoplasms including gliomas. It is relevant to explore these polymorphisms because certain carcinogenic exposures such as nitrosamines are implicated in the risk of gliomas. We therefore conducted a pilot case-control study to examine the role of polymorphisms in GSTM1, GSTT1, NAT2 (rapid, intermediate, and slow acetylation), and CYP1A1 and risk of glioma. Ninety patients diagnosed with glioma were ascertained as part of an ongoing genetic epidemiological study and were age, gender, and race matched with 90 healthy controls. We used PCR based methodology to determine the prevalence of the above genetic polymorphisms using sequences and PCR conditions directly adapted from studies reported previously. We calculated univariate odds ratios and performed multiple logistic regression to assess interactions between polymorphisms. We found no statistically significant associations between the null genotypes of GSTM1 and GSTT1, and CYP1A1 and risk of gliomas. However, there was an intriguing pattern with NAT2 acetylation status (odds ratios, 1.81, 1.34, and 0.61 for rapid, intermediate, and slow acetylation, respectively; P = 0.10 for trend). It is unlikely that any single polymorphism is sufficiently predictive of risk, and a panel of markers integrated with epidemiological data should be conducted on a large number of study subjects to fully understand the role of genetic polymorphisms and brain tumor risk.

Adult↗
PubMed1997

Comparison of model-free linkage mapping strategies for the study of a complex trait.

We compared several strategies for identifying and estimating effects from a genetic locus in the etiology of a complex trait. For our analyses we used data from simulated trait 1 and chromosome 5. Results from analysis of the first 20 replicates showed that a components of variance test provided considerably better power for identifying linkage than tests that consider pair differences. We also compared the power from constructing tests with a single marker, an approximate method using five markers jointly, or a multipoint analysis using all 25 markers on chromosome 5 jointly. Results from this analysis showed substantially better power when all markers were jointly used in the analysis. Results from considering all replicates showed that all methods of estimation provided maximal test statistics at the correct marker position, but the components of variance procedure provided more power to detect the correct position than other methods.

Analysis of Variance↗
PubMed1997

Assessing linkage on chromosome 5 using components of variance approach: univariate versus multivariate.

We report results when one disease related quantitative trait (Q1) is analyzed versus multiple related quantitative traits using a components of variance approach [Amos, 1994; de Andrade and Amos, 1996]. In both cases, we used age, sex and environmental factor (EF) as covariates. Analysis with ascertainment correction of samples selected through probands with extremely high trait values was also performed and is presented. Testing procedures to detect linkage using the components of variance approach are discussed. The univariate and multivariate analyses showed effects of locus 15 on chromosome 5 only for Q1. This result was confirmed when using ascertainment correction.

Analysis of Variance↗
PubMed1997

Genetic regulation of the capacity to make immunoglobulin G to pneumococcal capsular polysaccharides.

BACKGROUND: Genetic regulation of immunoglobulin G(IgG) responses to pneumococcal capsular polysaccharides (PPS), has been demonstrated in mice but not in humans. Earlier studies from this laboratory showed that healthy adults have a varying capacity to generate IgG antibody to PPS; this study sought to determine whether this capacity is genetically controlled. METHODS: A 23-valent pneumococcal vaccine was administered to 72 unrelated White adults, 4 nuclear families, and 61 members of an extended Ashkenazic Jewish family. Selected individuals later received one or more doses of the vaccine and/or a single dose of protein-conjugated PPS. Four to six weeks after each vaccination, IgG to PPS was measured by ELISA. Immunoglobulin allotypes and HLA types were determined by standard techniques. RESULTS: After vaccination, 53% of the 72 unrelated White adults had measurable levels of IgG antibody to all of 10 PPS studied (high-level responders), 36% had IgG to 6-9 PPS, and 11% had IgG to < or = 5 of 10 PPS (low-level responders). Persons who did not make IgG to an individual PPS also failed to make IgM or IgA to that antigen. Low-level responders had reduced mean IgG levels to PPS to which they did make IgG; nevertheless, their total serum concentrations of IgG, IgG2, IgA, and IgM were normal, and each made IgG2 to at least one PPS, all indicating that a global defect in Ig production was not responsible. The responder status of offspring was highly associated with that of their parents. Segregation analysis of 61 Ashkenazic family members revealed that the capacity to generate anti-PPS IgG was inherited in a mixed, codominant fashion. Repeated vaccination or administration of protein-conjugated PPS did not elicit measurable IgG in nonresponders. The HLA type was not associated with antibody responses. An association between IgG level and Gm(23)+ allotype was observed in unrelated Whites but not in Ashkenazic Jews. CONCLUSIONS: Thus, humans exhibit a variable capacity to respond to PPS. This response is hereditable in a mixed, codominant fashion. The absence of IgG to a PPS, even after antigen is presented in a protein-conjugate form, may reflect a genetically mediated failure to recognize polysaccharide antigens. Since persons who respond to fewer PPS also have lower levels of IgG to PPS to which they do respond, genetically determined deficiencies in events that involve proliferation of committed B lymphocytes may also play a role.

Adolescent↗
PubMed1996

Mutagen sensitivity and risk of gliomas: a case-control analysis.

Although the risk factors contributing to the etiology of brain tumors remain largely unknown, this pilot study suggests that genetically determined sensitivity to environmental carcinogens may play a role in the pathogenesis of these tumors. In this study, we examined short-term lymphocyte cultures from 45 adult malignant glioma patients and 117 age-, sex-, and ethnicity-matched healthy controls for mutagen-induced chromatid breaks and evaluated their family history of cancer, smoking, and demographic variables to ascertain the association between mutagen sensitivity and risk of brain tumors. The mutagen selected was gamma-radiation. The mean number of induced breaks/cell was 0.72 (SD=0.45) for the cases and 0.45 (SD = 0.35) for the controls (P < 0.0001). Using the median number of induced breaks/cell in the controls as the breakpoint for defining mutagen sensitivity, we observed an unadjusted odds ratio of 5.36 (95% confidence interval = 2.12-13.69) for mutagen sensitivity and brain tumor risk and an adjusted odds ratio of 5.79 (2.26-14.83), when we controlled for epidemiological risk factors including smoking, race, income, and education. Although a larger study is needed to confirm this intriguing result, these preliminary findings suggest that increased sensitivity to radiation is an independent risk factor for gliomas.

Adult↗
PubMed1996

Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues.

The etiology of the majority of human breast cancers is unknown; however, oxidative stress and lipid peroxidation have been suggested to play a role in breast carcinogenesis. To address this possibility, DNA adducts induced by malondialdehyde (MDA), an end product of lipid peroxidation, were analyzed in surgical specimens of normal breast tissues of 51 breast cancer patients using the nuclease P1-enhanced version of the 32P-postlabeling assay. Normal breast tissue samples from 28 noncancer patients receiving reduction mammoplasty served as controls. Two previously characterized putative MDA-deoxyadenosine (dA) and one MDA-deoxyguanosine adduct were detected in all tissue samples examined. Normal breast tissues from cancer patients exhibited significantly higher levels of the putative MDA adducts [median (42.5) and range (2.2-202.8) of relative adduct labeling x 10(9) values] than those found in noncancer controls (median, 15.67; range, 2.4-382.1; P = 0.0001, Mann-Whitney U test). Ten of the 51 cancer patients and 1 of the 28 controls were found to contain the putative MDA adducts at the level of > 1/10(7) nucleotides, a frequency comparable to that found in human liver. Age and body mass did not significantly influence the levels of these adducts. However, the presence of a previously detected benzo(a)pyrene-like DNA adduct in the breast tissues was associated with higher levels of the putative MDA-dA adducts in cancer patients (P = 0.012). The level of the putative MDA-dA adducts was significantly lower in smokers and former smokers compared to nonsmokers among cases after adjusting for age, body mass index, and status of the benzo(a)pyrene-like adduct (P = 0.009). Tumor tissues (n = 11) displayed significantly lower levels of the putative MDA adducts (median, 10.2; range, 5.3-20.6) than their corresponding normal adjacent tissues (median, 25.5; range, 10.5-138; P < 0.01). These findings provide evidence that lipid peroxidation products can accumulate in human breast tissues and reach relatively high levels in the breast tissues of women with breast cancer. There seems to be an interaction between these endogenous DNA modifications and carcinogen exposure-induced DNA adducts. Detection and quantitation of the putative MDA-DNA adducts may potentially be a useful tool in the understanding of breast cancer etiology.

Adult↗