Biomedical subjects

Jeannette T Bensen

Publications and source records attributed to Jeannette T Bensen.

8 recordsLinked to original sources

PubMed2006

The North Carolina-Louisiana Prostate Cancer Project (PCaP): methods and design of a multidisciplinary population-based cohort study of racial differences in prostate cancer outcomes.

BACKGROUND: The North Carolina-Louisiana Prostate Cancer Project (PCaP) is a multidisciplinary study of social, individual, and tumor-level causes of racial differences in prostate cancer aggressiveness. METHODS: A population-based sample of incident prostate cancer cases from North Carolina and Louisiana will include 1,000 African Americans and 1,000 Caucasian Americans. Study nurses administer structured questionnaires and collect blood, adipose tissue, urine, and toenail samples during an in-home visit. Clinical data are abstracted from medical records, diagnostic biopsies are reviewed and assayed, and tissue microarrays are constructed from prostatectomy samples. Prostate cancer aggressiveness is classified based on PSA, clinical stage, and Gleason grade. RESULTS: Preliminary data demonstrate between- and within-group differences in patient characteristics, screening, and treatment by race and state. Participation exceeds 70% in all groups. CONCLUSIONS: Preliminary data support the feasibility of this comprehensive study to help determine the focus of public health efforts to reduce racial disparities in prostate cancer mortality.

Black People↗

PubMed2006

Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York.

The gene encoding catechol-O-methyltransferase (COMT), critical to the inactivation of reactive catechol estrogens, has several single nucleotide polymorphisms (SNPs) that influence enzyme activity. A 3-SNP haplotype (IVS1+255 C>T; Ex4-12 G>A; 3'UTR-521 A>G), which has been shown to reduce COMT expression in the human brain, has been identified. To evaluate the influence of genetic variation of COMT on breast cancer risk, these 3-SNPs were genotyped in 1052 cases and 1098 controls. We estimated the associations between breast cancer and individual SNPs, as well as, multilocus haplotypes. We also examined surrogates of hormone exposure as potential modifiers of the putatively functional Ex4-12 SNP-breast cancer association. Odds ratios (OR) and 95% confidence intervals (CI) were based on age-adjusted unconditional logistic regression models. We found no association between the individual SNPs alone and breast cancer. When examining the association between breast cancer and the 3-SNP haplotypes, we observed a 19% increase in risk associated with each copy of the TGG haplotype (OR=1.19, 95% CI 0.96-1.49), relative to the common TAA haplotype, which was statistically significant when assuming a dominant model (OR=1.32, 95% CI 1.05-1.67, p-value=0.02). In this report of COMT haplotypes and breast cancer, we found some evidence that additional genetic variability beyond the Ex4-12 G>A SNP contributes to risk of breast cancer among a small subgroup of women; however, these results need to be replicated in additional studies.

Adult↗

PubMed2005

MnSOD Val-9Ala genotype, pro- and anti-oxidant environmental modifiers, and breast cancer among women on Long Island, New York.

Excessive oxidative stress may induce and promote breast carcinogenesis. Manganese superoxide dismutase (MnSOD) is critical to management of oxidative stress by catalyzing the formation of hydrogen peroxide from two superoxide anions. To examine the relationship between MnSOD Val-9Ala polymorphism, breast cancer and potential modifiers, we analyzed data from a large population-based case-control study. Study participants completed an in-home interviewer-administered questionnaire, and self-completed a Block food frequency questionnaire. Age-adjusted unconditional logistic models included 1034 cases and 1084 controls. As compared with Val/Val genotype, we found no association between MnSOD Ala/Val (OR = 0.98, 95% CI: 0.79-1.21) and Ala/Ala (OR = 1.00, 95% CI: 0.79-1.28) genotypes and breast cancer. Results did not differ by menopausal status, stage of tumor, or estrogen and progesterone receptor status. No discernable patterns of interaction were found between this MnSOD variant and anti-oxidative exposures, including fruit and vegetable intake or NSAID use, or pro-oxidant exposures, including smoking and alcohol. This study provides little evidence that variation in Val-9Ala polymorphism of MnSOD alone or through substantial interaction with key exposures believed to be pro- or anti-oxidant properties influences breast cancer risk.

Aged↗

PubMed2004

Association analysis of the plasminogen activator inhibitor-1 4G/5G polymorphism in Hispanics and African Americans: the IRAS family study.

OBJECTIVE: Plasminogen activator inhibitor type-1 (PAI-1) plays a central role in fibrolysis and has recently been hypothesized to influence components of the insulin resistance syndrome. We consider whether the 4G/5G polymorphism influences components of insulin resistance and obesity solely through PAI-1 protein levels or also though a secondary pathway. In addition, we explore whether transforming growth factor (TGF-beta1), a key regulator of PAI-1 expression, modifies the influence of the PAI-1 4G/5G polymorphism on these traits. METHODS AND RESULTS: The Insulin Resistance and Atherosclerosis (IRAS) Family Study genotyped 287 African American (18 pedigrees) and 811 Hispanic American (45 pedigrees) individuals for the 4G/5G PAI-1 and two TGF-beta1 polymorphisms (R25P, C-509T). Individuals were recruited from three clinical centers located in San Antonio (urban Hispanic), San Luis Valley (rural Hispanic) and Los Angeles (African American). The presence of the 4G PAI-1 allele was positively associated with PAI-1 protein level (combined sample p < 0.0001). Hispanic Americans average 65% higher PAI-1 protein levels than African Americans (p < 0.0001). Consistently across ethnic groups, increased PAI-1 protein levels were associated with increased insulin resistance and overall and central obesity (p value < 0.0001, combined sample). Adjusting for PAI-1 protein levels, there was evidence of an association of PAI-1 genotype (4G) with insulin sensitivity (p < 0.002) and subcutaneous fat (p < 0.01). These associations were not influenced by TGF-beta1 genotypes. CONCLUSIONS: PAI-1 protein is a strong correlate of insulin resistance (IR) and obesity in Hispanics and African Americans. However, PAI-1 4G/5G polymorphism appears to influence insulin resistance and obesity beyond its direct influence on serum PAI-1 protein levels.

Black or African American↗

PubMed2003

Exploring pleiotropy using principal components.

A standard multivariate principal components (PCs) method was utilized to identify clusters of variables that may be controlled by a common gene or genes (pleiotropy). Heritability estimates were obtained and linkage analyses performed on six individual traits (total cholesterol (Chol), high and low density lipoproteins, triglycerides (TG), body mass index (BMI), and systolic blood pressure (SBP)) and on each PC to compare our ability to identify major gene effects. Using the simulated data from Genetic Analysis Workshop 13 (Cohort 1 and 2 data for year 11), the quantitative traits were first adjusted for age, sex, and smoking (cigarettes per day). Adjusted variables were standardized and PCs calculated followed by orthogonal transformation (varimax rotation). Rotated PCs were then subjected to heritability and quantitative multipoint linkage analysis. The first three PCs explained 73% of the total phenotypic variance. Heritability estimates were above 0.60 for all three PCs. We performed linkage analyses on the PCs as well as the individual traits. The majority of pleiotropic and trait-specific genes were not identified. Standard PCs analysis methods did not facilitate the identification of pleiotropic genes affecting the six traits examined in the simulated data set. In addition, genes contributing 20% of the variance in traits with over 0.60 heritability estimates could not be identified in this simulated data set using traditional quantitative trait linkage analyses. Lack of identification of pleiotropic and trait-specific genes in some cases may reflect their low contribution to the traits/PCs examined or more importantly, characteristics of the sample group analyzed, and not simply a failure of the PC approach itself.

Blood Pressure↗

PubMed2003

Nucleotide variation, haplotype structure, and association with end-stage renal disease of the human interleukin-1 gene cluster.

A dense gene-based SNP map was constructed across a 360-kb region containing the interleukin-1 gene cluster (IL1A, IL1B, and IL1RN), focusing on IL1RN. In total, 95 polymorphisms were confirmed or identified primarily by direct sequencing. Polymorphisms were precisely mapped to completed BAC and genomic sequences spanning this region. The polymorphisms were typed in 443 case-control subjects from Caucasian and African American groups. Consecutive pair-wise marker linkage disequilibrium was not strictly correlated with distance and ranged from D'=0.0079 to 1.000 and D'=0.0521 to 1.0000 in Caucasians and African Americans, respectively. Single markers and haplotypes in IL1 cluster genes were evaluated for association with end-stage renal disease (ESRD). Eleven SNPs show some evidence of association with ESRD, with the strongest associations in two IL1A variants, one SNP, rs1516792-3, in intron 5 (p=0.0015) and a 4-bp insertion/deletion within the 3'UTR, rs16347-2 (p=0.0024), among African Americans with non-T2DM-associated ESRD.

Black or African American↗

PubMed2003

Exclusion of candidate genes in two families with autosomal dominant hypocalcified amelogenesis imperfecta.

The amelogenesis imperfectas (AI) are a group of hereditary enamel defects characterized by clinical and genetic diversity. The most common AI types are inherited as autosomal traits. Three mutations of the enamelin (ENAM) gene have been found in cases of autosomal dominant hypoplastic AI. The gene(s) responsible for hypocalcified forms of AI have not been identified, although a number of autosomal genes have been proposed as candidates for AI based on their expression by ameloblasts, including ameloblastin and enamelin (chromosome 4q13.3), tuftelin (chromosome 1q21), enamelysin (chromosome 11q22.3-q23) and kallikrein 4 (chromosome 19q13.3-q13.4). To localize the gene(s) responsible for autosomal dominant hypocalcified AI, we evaluated support for/against linkage of AI to genetic markers spanning five AI candidate genes in two extended families. Our data excluded all proposed candidate gene regions as causal for autosomal dominant hypocalcified AI in these families. These linkage findings provide further evidence for genetic heterogeneity among families with autosomal dominant AI and indicate that, at least, some forms of autosomal dominant hypocalcified AI are not caused by a gene in the five most commonly reported AI candidate genes.

Amelogenesis Imperfecta↗

PubMed2003

Association of an IL-1A 3'UTR polymorphism with end-stage renal disease and IL-1 alpha expression.

BACKGROUND: We evaluated polymorphisms in the interleukin-1 alpha 3'-untranslated region (IL-1A 3'[UTR]) for association with type 2 diabetes-associated (DM) and nondiabetic-associated (non-DM) end-stage renal disease (ESRD) in two ethnic groups. METHODS: IL-1A 3'UTR polymorphisms were identified by alignment of overlapping human expressed sequence tags (ESTs). Sequence ambiguities were experimentally confirmed and variants genotyped to test for association with ESRD in 75 unrelated Caucasians with DM ESRD, 95 unrelated Caucasian controls and, in a parallel study, 92 unrelated African Americans with type 2 DM ESRD, 95 unrelated African Americans with non-DM ESRD, and 86 unrelated African American controls. IL-1A 3' UTR genotype and lipopolysaccharide (LPS)-stimulated IL-1 alpha protein levels were measured in healthy Caucasians (N = 112) and African Americans (N = 101) to evaluate association between genotype and protein level. RESULTS: A polymorphism in the 3' UTR of the human IL-1A gene was associated with ESRD and IL-1 alpha protein expression. The polymorphism consists of two single nucleotide polymorphisms (SNPs) and an insertion/deletion generating four different haplotypes: TN7TTCAA, AN7TTCAA, TN7TTCAG and an allele deleted for four internal bases, TN7(delTTCA)A. The 4 bp deletion allele, TN7(delTTCA)A, was significantly less common among Caucasian DM ESRD and African American non-DM ESRD patients (recessive model; P = 0.0364 and P = 0.0293, respectively). In vitro, this polymorphism is associated with the amount of IL-1 alpha protein synthesized in LPS-stimulated lymphocytes from healthy subjects (P = 0.0013, additive model), with the TN7(delTTCA)A haplotype associated with higher levels of stimulated IL-1 alpha. CONCLUSION: The association of the TN7(delTTCA)A haplotype with higher levels of IL-1 alpha expression and reduced risk for ESRD is consistent with involvement of cytokines in risk for developing nephropathy.

3' Untranslated Regions↗