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M de Andrade

Publications and source records attributed to M de Andrade.

At least 19 recordsLinked to original sources
PubMed2005

Education and occupations preceding Parkinson disease: a population-based case-control study.

OBJECTIVE: To investigate the association of Parkinson disease (PD) with education and occupations using a case-control study design. METHODS: The authors used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. The authors collected information about education and occupations using two independent sources of data: a review of the complete medical records in the system and a telephone interview. Occupations were coded using the 1980 Standard Occupational Classification. RESULTS: Subjects with 9 or more years of education were at increased risk of PD (OR = 2.0; 95% CI = 1.1 to 3.6; p = 0.02), and there was a trend of increasing risk with increasing education (test for linear trend, p = 0.02; medical records data). Physicians were at significantly increased risk of PD using both sources of occupational data. By contrast, four occupational groups showed a significantly decreased risk of PD using one source of data: construction and extractive workers (e.g., miners, oil well drillers), production workers (e.g., machine operators, fabricators), metal workers, and engineers. These associations with increased or decreased risk did not change noticeably after adjustment for education. CONCLUSION: Subjects with higher education and physicians have an increased risk of Parkinson disease (PD), while subjects with some occupations presumed to involve high physical activity have a decreased risk of PD.

Adult↗
PubMed2005

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis.

Interferon-gamma (IFNgamma) treatment is deleterious in multiple sclerosis (MS). MS occurs twice as frequently in women as in men. IFNgamma expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1(761)*CAn], a single nucleotide polymorphism 3' of IFNG [3'(325)*G --> A] and three flanking microsatellite markers spanning a 118 kb region around IFNG. Men carriers of the 3'(325)*A allele have increased susceptibility to MS compared to noncarriers in the USA (P=0.044; OR: 2.58, 95% CI: 0.97-8.08) and Northern Ireland (P=0.019; OR: 2.37, 95% CI: 1.10-5.13). There is a nonsignificant trend in the same direction in Belgian men (P=0.299; OR: 1.50, 95% CI: 0.71-3.26). Men carriers of I1(761)*CA13, which is in strong linkage disequilibrium with the 3'(325)*A, have increased susceptibility (P=0.050; OR: 2.22, 95% CI: 0.98-5.40), while men carriers of I1(761)*CA12 have decreased susceptibility (P=0.022; OR: 0.46, 95% CI: 0.23-0.90) to MS in the USA. Similar associations were reported in Sardinia between the I1(761)*CA12 allele and reduced risk of MS in men. Flanking markers were not associated with MS susceptibility. Polymorphisms of IFNG may contribute to differences in susceptibility to MS between men and women.

3' Flanking Region↗
PubMed2004

A limited role for DJ1 in Parkinson disease susceptibility.

An association study of four common polymorphisms in the DJ1 gene and Parkinson disease (PD) was conducted. PD probands were compared with their unaffected siblings matched by gender and closest age at study (416 vs 416) and with unrelated control subjects (691 vs 190). None of the four haplotype tagging single-nucleotide polymorphisms (SNPs) was associated with PD overall, but SNP1 (position 4,345 bp) and SNP3 (position 16,491 bp) were associated with PD in women (p = 0.03 and p = 0.002).

Adult↗
PubMed2004

A major lung cancer susceptibility locus maps to chromosome 6q23-25.

Lung cancer is a major cause of death in the United States and other countries. The risk of lung cancer is greatly increased by cigarette smoking and by certain occupational exposures, but familial factors also clearly play a major role. To identify susceptibility genes for familial lung cancer, we conducted a genomewide linkage analysis of 52 extended pedigrees ascertained through probands with lung cancer who had several first-degree relatives with the same disease. Multipoint linkage analysis, under a simple autosomal dominant model, of all 52 families with three or more individuals affected by lung, throat, or laryngeal cancer, yielded a maximum heterogeneity LOD score (HLOD) of 2.79 at 155 cM on chromosome 6q (marker D6S2436). A subset of 38 pedigrees with four or more affected individuals yielded a multipoint HLOD of 3.47 at 155 cM. Analysis of a further subset of 23 multigenerational pedigrees with five or more affected individuals yielded a multipoint HLOD score of 4.26 at the same position. The 14 families with only three affected relatives yielded negative LOD scores in this region. A predivided samples test for heterogeneity comparing the LOD scores from the 23 multigenerational families with those from the remaining families was significant (P=.007). The 1-HLOD multipoint support interval from the multigenerational families extends from C6S1848 at 146 cM to 164 cM near D6S1035, overlapping a genomic region that is deleted in sporadic lung cancers as well as numerous other cancer types. Parametric linkage and variance-components analysis that incorporated effects of age and personal smoking also supported linkage in this region, but with somewhat diminished support. These results localize a major susceptibility locus influencing lung cancer risk to 6q23-25.

Chromosome Mapping↗
PubMed2004

Glutathione pathway genes and lung cancer risk in young and old populations.

Multiple enzymes with overlapping functions and shared substrates in the glutathione (GSH) metabolic pathway have been associated with host susceptibility to tobacco smoke carcinogens and in lung cancer etiology. However, few studies have investigated the differing and interacting roles of GSH pathway enzymes with tobacco smoke exposure on lung cancer risk in young (<50 years of age) and old (>80 years of age) populations. Between 1997 and 2001, 237 primary lung cancer patients (170 young, 67 old) and 234 controls (165 young, 69 old) were enrolled at the Mayo Clinic. Using PCR amplification of genomic DNA, polymorphic markers for gammaGCS, GPX1, GSTP1 (I105V and A114V), GSTM1 and GSTT1 were genotyped. Recursive partitioning and logistic regression models were used to build binary classification trees and to estimate odds ratios (OR) and 95% confidence intervals for each splitting factor. For the young age group, cigarette smoking had the greatest association with lung cancer (OR = 3.3). For never smokers, the dividing factors of recursive partitioning were GSTT1 (OR = 1.7), GPX1 (OR = 0.6) and GSTM1 (OR = 4.3). For the old age group, smoking had the greatest association with lung cancer (OR = 3.6). For smokers, the dividing factors were GPX1 (OR = 3.3) and GSTP1 (I105V) (OR = 4.1). Results from logistic regression analyses supported the results from RPART models. GSH pathway genes are associated with lung cancer development in young and old populations through differing interactions with cigarette smoking and family history. Carefully evaluating multiple levels of gene-environment and gene-gene interactions is critical in assessing lung cancer risk.

Acyltransferases↗
PubMed2004

Environmental tobacco smoke exposure in women with lung cancer.

BACKGROUND: Investigations on environmental tobacco smoke (ETS) exposure that include source intensity, childhood exposure, and association with histologic subtypes among never smoking lung cancer cases are limited. We report the patterns of ETS exposure history in a clinical cohort of women with newly diagnosed lung cancer. METHODS: From 1997 to 2001, 810 women with lung cancer were interviewed to obtain data including the source, intensity, and duration of ETS exposure. In this descriptive study, relationships between smoking history, ETS exposure, and lung cancer histologic subtypes were analyzed. RESULTS: Among the 810 patients, 773 (95.4%) reported personal smoking or ETS exposure including 170 of 207 (82%) never smokers. Among the never smokers with a history of ETS exposure, the mean years of exposure were 27 from a smoking spouse, 19 from parents, and 15 from co-workers. For each major subtype of lung cancer (adenocarcinoma, squamous cell, unclassified non-small cell lung cancer, small cell, or carcinoids) among never smokers, 75-100% of patients had ETS exposure. Trends for adenocarcinoma, squamous, and small cell carcinoma are statistically significant using the Cochran-Armitage Test for Trend (P<0.001) among never smokers without ETS exposure, never smokers with ETS exposure, former smokers, and current smokers. CONCLUSIONS: Over 95% of women with lung cancer in our study were exposed to tobacco smoke through a personal smoking history or ETS. The cumulative amount of tobacco smoke exposure may be significantly underestimated if only personal smoking history is considered. Our results add to the public health implications of exposure to tobacco smoke and highlight the importance of eliminating tobacco smoking in public and private settings.

Adult↗
PubMed2001

Gamma-radiation sensitivity and risk of glioma.

BACKGROUND: About 9% of human cancers are brain tumors, of which 90% are gliomas. gamma-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the gamma-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma. METHODS: We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We gamma-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. RESULTS: We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001). CONCLUSION: gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.

Adult↗
PubMed2001

alpha-Synuclein gene haplotypes are associated with Parkinson's disease.

We report haplotype analysis of the alpha-synuclein gene in Parkinson's disease (PD), extending earlier reports of an association with a polymorphism within the gene promoter. This analysis showed significant differences in haplotypes between PD cases and controls. Our analyses demonstrate that genetic variability in the alpha-synuclein gene is a risk factor for the development of PD. These genetic findings are analogous to the tau haplotype over-represented in progressive supranuclear palsy and further extend the similarity in the etiologies and pathogeneses of the synucleinopathies and tauopathies.

Adult↗
PubMed2001

Risk assessment for developing gliomas: a comparison of two cytogenetic approaches.

Chromosome instability (CIN) measured as chromosome aberrations has long been suggested as a cancer susceptibility biomarker. Conventional cytogenetic end-points are now being improved by combining molecular methods, which increases the sensitivity, specificity, and precision of the assay. In this study we examined both spontaneous and gamma-ray induced CIN in lymphocyte cultures from 51 previously untreated glioma patients and 51 age-, sex- and ethnicity-matched controls. CIN was assessed using two parallel methods: (1) the mutagen sensitivity (MS) assay and (2) the multicolor fluorescence in situ hybridization (FISH) assay. The frequency of spontaneous breaks was significantly higher in glioma patients (mean+/-S.D., 2.12+/-1.07) than in controls (1.24+/-0.86, P<0.001) when using the FISH assay but not the MS assay (0.019+/-0.02 and 0.019+/-0.01, respectively; P=0.915). Similarly, the frequency of induced chromatid breaks was significantly higher using the FISH assay (3.39+/-1.72) but not the MS assay (0.42+/-0.16) in the patients versus controls (2.08+/-1.18 and 0.37+/-0.15, respectively; P<0.001 and P=0.10, respectively). By using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (ORs) of 5.13 (95% CI=2.23-12.1) for spontaneous and 4.86 (95% CI=2.08-11.4) for induced CIN using the FISH assay, whereas the ORs were 1.32 (95% CI=0.49-3.58) and 1.28 (95% CI=0.59-2.80) for spontaneous and induced CIN using the MS assay. There was also a significant increase in the frequency of hyperdiploid cells in the glioma cases which could only be detected using the FISH assay (OR=4.0, 95% CL=0.9-17.0). By combining both methods an estimated risk of 7.0 (95% CI=1.7-25.6) was observed. There was no correlation between the breaks detected by the two methods suggesting that each method is a measure of a different event. The results indicate that using the multicolor FISH assay for detection of CIN in peripheral blood lymphocytes in glioma patients is a more useful marker for risk assessment.

Adult↗
PubMed2001

Segregation analysis of cancer in families of glioma patients.

A small proportion of brain tumors are attributed to a genetic predisposition; however, the hereditary proportion is undetermined. This study evaluates the degree of familial aggregation of cancer in a large series of brain tumor patients. Our study included 5,088 relatives of 639 probands (3,810 first- and 1,278 second-degree), diagnosed with a glioma between June 1992 and June 1995 at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, with diagnosis under age 65 years, and residents of the United States or Canada. We conducted an in-person or telephone interview with patients and/or their next-of-kin, and obtained family histories for the probands' first-degree (parents, siblings, offspring) and selected second-degree relatives (aunts, uncles, grandparents) using a sequential sampling strategy. Reported cancers were documented by medical records and/or death certificates (if the relative was deceased and medical records were unavailable). We conducted segregation analysis using the Pedigree Analysis Program (PAP). The analyses were divided into two categories: (1) all 639 families, and (2) a subset of families whose gliomas stained positive on p53 immunohistochemistry analysis. We demonstrated that a multifactorial Mendelian model was favored, while a model postulating a purely environmental cause of brain cancer was rejected. This study indicates that familial cancer in relatives of glioma patients are probably a result of multigenic action, and familial clustering of cancer among relatives of glioma patients may involve unknown environmental exposures.

Adolescent↗
PubMed2001

A comparison of software packages that assess linkage using a variance components approach.

We report single-point and multipoint results from three statistical genetics software packages using a variance components approach for quantitative traits. When possible, we have shown the effects of covariates. Results from GENEHUNTER, SOLAR, and ACT software packages are compared for the quantitative trait immunoglobulin E (IgE) using chromosome 5 asthma familial data from Oxfordshire (England), Perth (Australia), and Freiburg (Germany), and using the genome-wide German data. Although few differences among variance components results for GENEHUNTER, SOLAR, and ACT were detected on a limited region of chromosome 5, these packages showed larger disagreement in the German data for chromosomes 1, 9, and 14.

Adult↗
PubMed2001

Practical application of residuals from survival models in quantitative trait linkage analysis.

A number of familial diseases have an age-of-onset component, which can be considered as a censored quantitative trait. However, few software resources are available for the use of time-to-event endpoints in linkage analysis. The purpose of this analysis was to examine the use of martingale residuals from Cox survival models as quantitative traits for familial diseases with variable age at onset. We used these residuals as quantitative traits in variance components linkage scans for the 50 replicates of the general population simulated data for chromosomes 6 and 7. The region on chromosome 6 containing markers D06G034 and D06G035 demonstrated evidence for linkage, consistent with the underlying genetic model. This analysis demonstrates the applicability of using martingale residuals as a quantitative trait in linkage analyses of diseases that depend on age of onset.

Adult↗
PubMed2001

Comparison of multivariate tests for genetic linkage.

OBJECTIVES: Multivariate tests for linkage can provide improved power over univariate tests but the type I error rates and comparative power of commonly used methods have not previously been compared. Here we studied the behavior of bivariate formulations of the variance component (VC) and Haseman-Elston (H-E) approaches. METHODS: We compared through simulation studies the bivariate H-E test with the unconstrained bivariate VC approach and with a VC approach in which the major-gene correlation is constrained to +/-1. We also compared these methods to univariate methods. RESULTS: Bivariate approaches are more powerful than univariate analyses unless the traits are very highly positively correlated. The power of the bivariate H-E test was less than the VC procedures. The constrained test was often less powerful than the unconstrained test. The empirical distributions of the bivariate H-E test and the unconstrained bivariate VC test conformed with asymptotic distributions for samples of 100 or more sibships of size 4. CONCLUSIONS: The unconstrained VC test is valuable for testing for preliminary linkages using multivariate phenotypes. The bivariate H-E test was less powerful than the bivariate VC tests.

Computer Simulation↗
PubMed2001

Genetic linkage methods for quantitative traits.

We discuss methods for detecting genetic linkage for quantitative data. The usual LOD score method uses a pseudolikelihood formulation and has optimal power provided all parameters are correctly specified, but can lead to erroneous estimates of the location for the locus influencing a trait under misspecification of parameters describing the variance of the trait. Alternative methods, in which attention focuses upon modelling covariation among relatives as a function of genetic marker, similarity lead to unbiased estimates of the location and major gene heritability of the trait influencing locus. The Haseman-Elston approach uses a regression method to perform linkage analysis and its properties have been widely studied. This method is generally less powerful than variance components procedures, but the maximum likelihood-based variance components procedures require normality of the trait to ensure robustness of the genetic linkage tests (i.e. a correct false positive rate). When samples are non-randomly selected an ascertainment correction is generally required in order to obtain unbiased parameter estimates when applying variance components methods. For quantitative traits, ascertainment corrections usually condition either on the proband exceeding a threshold, or on the trait value of the proband. We summarize simulations that show that both approaches lead to similar efficiencies for estimating genetic effects. Finally, we discuss methods for analysing diseases that include time-to-onset information. A variety of methods are available for the linkage analysis of quantitative traits. Here, we have reviewed the most commonly used methods.

Biometry↗
PubMed2001

The impact of population admixture on traditional linkage analysis.

INTRODUCTION: Families of admixed ancestry are routinely excluded from traditional (Log of the Odds [LOD] score) linkage analysis or are analyzed as being derived from a homogeneous population using the proband's ethnicity. Using traditional linkage analysis with these families can cause complications due to the mixing of different disease rates and allele frequencies that occurs. The presence of admixture violates the key assumptions of Hardy-Weinberg Equilibrium (HWE) and Linkage Equilibrium (LE) invoked in the current methods of linkage analysis. If one or more of these assumptions are violated, incorrect inference for linkage could result. DESIGN AND METHODS: Through simulation, we investigated the effect of admixture of two populations on the LOD score under various conditions, using prostate cancer as our underlying disease model. Four-generation homogeneous and admixed families were simulated with 27 markers and two linked, bi-allelic disease loci. Two different types of admixture were tested: admixture within a family unit and a mixture of homogeneous families within a data set. All mixing was done at the founder level in three different proportions: 30/70, 50/50 and 70/30. RESULTS AND CONCLUSIONS: We observed that the LOD scores under both models of admixture were closest to the homogeneous family scores of the population having the highest mixing proportion. Random sampling of families or ascertainment of families with disease affection status did not affect this observation, nor did the mode of inheritance (dominant/recessive) or sample size. Thus, the presence of families of mixed population ancestry impacts linkage analysis in terms of the LOD score and the estimate of the recombination fraction.

Alleles↗
PubMed2000

Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations.

The purpose of this study was to examine the level of smoking-related aromatic DNA adducts and oxidative DNA damage in current smokers from a lung cancer case-control study in African Americans and Mexican Americans. In addition, mutagen sensitivity (bleomycin-induced chromatid breaks), a marker of genetic susceptibility, was assessed in these patients and correlated with the level of DNA damage. Lymphocyte DNA from cases and age-, sex-, and ethnicity-matched controls was analyzed for aromatic DNA adducts (43 cases and 47 controls) and the level of 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was determined in 46 cases and 48 controls using (32)P-postlabeling. Overall, lung cancer cases had significantly (P < 0.05) higher levels of aromatic DNA adducts and 8-oxo-dG (mean+/-SEM; 6.03+/-1.16/10(8) nucleotides and 5.82+/-0.77/10(5) nucleotides, respectively) compared to the controls (2.80+/-0.36/10(8) nucleotides and 3.65+/-0.56/10(5) nucleotides, respectively). The case-control differences for these two biomarkers were especially evident in current smokers. Both male and female lung cancer cases had higher levels of aromatic DNA adducts compared to the corresponding controls but only in men was the difference statistically significant (P=0.002). Cases who started smoking at earliest age had highest levels of aromatic DNA adducts and 8-oxo-dG. The level of aromatic DNA adducts in lung cancer cases, but not controls, was positively correlated with bleomycin-induced chromatid breaks (P=0.011). In contrast, the level of 8-oxo-dG was not correlated with mutagen sensitivity in either cases or controls or with the level of aromatic DNA adducts. The data suggest that levels of both aromatic DNA adducts and 8-oxo-dG may be useful in predicting risk of lung cancer in these minority populations. The correlation between aromatic DNA adducts and mutagen sensitivity in lung cancer cases and the trend for higher levels of DNA damage in cancer cases who started smoking earliest are particularly interesting and merit further study.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Ascertainment issues in variance components models.

One of the main concerns in the family studies of complex diseases is the effect that ascertainment and correction for it may have on test procedures and estimators. Elston and Sobel [1979] and Hopper and Mathews [1982] proposed two ways to correct for ascertainment in the study of quantitative trait data. For single ascertainment, using a variance components approach, we present results of simulation studies comparing estimates from these two methods for different selection criteria. We also show results from simulations when ascertained families are analyzed either at random or by correcting for ascertainment. For discordant sibpairs, we compare a variance components model that incorporates ascertainment correction with the extreme discordant sib pairs (EDSP) design proposed by Risch and Zhang [1995]. Our results show that there is minimal difference between the two methods of ascertainment correction. In the presence of effects from a large genetic background and the segregation of a rare gene, both ascertainment affected the polygenic and environmental components of variance but had rather little impact on the estimate of the linked major gene component of variance. The results also show the EDSP is slightly more powerful the variance components procedures for common alleles, and the variance components procedure is much more powerful than using EDSP when there is a rare allele segregating in the population.

Family Health↗