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Biomedical subjects

B Newman

Publications and source records attributed to B Newman.

At least 19 recordsLinked to original sources
PubMed2000

Linkage of the cholesteryl ester transfer protein (CETP) gene to LDL particle size: use of a novel tetranucleotide repeat within the CETP promoter.

BACKGROUND: A preponderance of small, dense LDL particles, elevated levels of plasma triglycerides (TG), and low levels of HDL characterize the atherogenic lipoprotein phenotype, which is associated with increased coronary artery disease (CAD) risk. Genetic and environmental factors influence LDL size, cholesteryl ester transfer protein (CETP) being one of the candidate genes. CETP mediates the transfer of cholesteryl ester from HDL to apolipoprotein (apo) B-containing lipoproteins in exchange for TG, promoting reverse cholesterol transfer and remodeling of lipoprotein particles. METHODS AND RESULTS: We have identified a tetranucleotide repeat (fragment sizes from 324 to 464 bp; heterozygosity index = 0.74) within the CETP promoter and used it in quantitative sib-pair linkage analysis in 119 female dizygotic (DZ) twins. Linkage was found to LDL size (P<0.001), TG (P<0.005), and plasma apoB (P = 0.02). The distribution of the tetranucleotide repeats was bimodal, and there was strong allelic association of the "short" alleles with the B2 allele of CETP TaqIB polymorphic site (P<0.001). CONCLUSIONS: This report of linkage of the CETP gene to LDL particle size adds to the list of candidate genes linked to LDL size, supporting the hypothesis of multigenic determination of LDL size heterogeneity. Whether this promoter variation is itself functional or is a marker for a functional site in the CETP gene remains to be determined.

Apolipoproteins↗
PubMed2000

Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status.

Risk factors were examined for subgroups of breast cancer characterized by estrogen receptor (ER) and progesterone receptor (PR) status. Data from the Carolina Breast Cancer Study, a population-based, North Carolina case-control study of 862 breast cancer cases aged 20-74 years diagnosed during 1993-1996 and 790 controls frequency matched on race and age, were obtained by personal interview. ER and PR status was retrieved from medical records (80%) or was determined in the authors' laboratory (11%) but was missing for 9% of cases. The receptor status distribution was as follows: 53% ER+PR+, 11% ER+PR-, 8% ER-PR+, and 28% ER-PR-. Several hormone-related factors were associated with stronger increased risks for ER+PR+ than for ER-PR- breast cancer: the elevated odds ratios were strongest for ER+PR+ breast cancer among postmenopausal women who had an early age at menarche (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.4), nulliparity/late age at first full-term pregnancy (OR = 1.7, 95% CI: 0.9, 3.2 and OR = 1.6, 95% CI: 1.0, 2.7, respectively), or a high body mass index (OR = 1.6, 95% CI: 0.9, 3.0) and among pre-/perimenopausal women who had a high waist-hip ratio (OR = 1.9, 95% CI: 1.2, 3.1). In contrast, family history of breast or ovarian cancer and medical radiation exposure to the chest produced higher odds ratios for ER-PR- than for ER+PR+ breast cancer, especially among pre-/perimenopausal women.

Adult↗
PubMed2000

Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans.

We examined the role of constitutional genetic variation at the UDP-glucuronosyltransferase (UGT) 1A1 locus in breast cancer susceptibility. The UGT1A1 enzyme is a major UGT involved in estradiol glucuronidation. To date, four UGT1A1 variant alleles characterized by a variation in the number of TA from five through eight repeats in the atypical TATA box region have been described in the African-American population. Functional analyses of the transcriptional activity in breast and liver cells revealed that the transcription activation of a reporter gene is inversely correlated with the number of repeats. Reverse transcription-PCR analysis confirmed the expression of UGT1A1 in human liver in the hepatocarcinoma cell line HepG2 and provided evidence of the expression of UGT1A1 in breast cancer tissue, where a positive signal was observed in 11 of 12 breast cancer cell lines tested. The population-based case-control study involved 200 women with breast cancer and 200 female controls of African ancestry. We postulated that breast cancer cases might have a higher prevalence of low activity allele-containing genotypes than controls (alleles presenting seven and eight repeats in the A(TA)nTAA motif of the TATA box). The age-adjusted odds ratio (OR) for breast cancer comparing women with seven and eight allele-containing genotypes versus 5/5, 5/6, and 6/6 genotypes was 1.8 [95% confidence interval (CI), 1.0-3.1; P = 0.06] in premenopausal women and 1.0 (95% CI, 0.5-1.7; P = 0.9) in postmenopausal women. The observed 1.8-fold elevated risk in premenopausal women with invasive breast cancer is highly suggestive of a possible interaction between UGT genotype and hormones. Additional analyses suggested a stronger association of UGT1A1 genotype with estrogen receptor (ER)-negative breast cancer. Among premenopausal women, the association was stronger for ER- breast cancer (OR, 2.1; 95% CI, 1.0-4.2; P = 0.04) than ER+ breast cancer (OR, 1.3; 95% CI, 0.6-3.0; P = 0.5). The OR was slightly stronger among women who used oral contraceptives, and the association remained null in postmenopausal women, regardless of whether they took hormone replacement therapy. Our current findings suggest that further investigations are warranted to elucidate the role of UGT1A1 in breast cancer risk.

Adult↗
PubMed2000

The associations of adolescent cigarette smoking, alcoholic beverage consumption, environmental tobacco smoke, and ionizing radiation with subsequent breast cancer risk (United States).

OBJECTIVES: Studies of breast cancer among survivors of the World War II atomic bomb blasts over Japan suggest that the adolescent breast may be particularly sensitive to carcinogenic insult. To further explore that possibility we examined the relationships of cigarette smoking, alcohol consumption, environmental tobacco smoke (ETS) exposure, and medical treatment with ionizing radiation during adolescence with subsequent breast cancer risk. METHODS: Data from the Carolina Breast Cancer Study, a population-based, case-control study of breast cancer in North Carolina women aged 20-74 years (864 cases, 790 controls), were analyzed. RESULTS: A modest increase in breast cancer risk was suggested for women who began to smoke cigarettes between the ages of 10 and 14 years (OR: 1.5, CI: 0.9-2.5), and for women exposed to ionizing radiation between ages 10 and 19 years to treat or monitor a medical condition (OR: 1.6, CI: 0.5-2.5). Neither exposure to ETS at home prior to age 18 years (OR: 1.1, CI: 0.9-1.3) nor initiation of alcoholic beverage consumption between ages 10 and 15 years (OR: 1.1, CI: 0.6-1.8) appeared to increase risk. CONCLUSIONS: Our results are consistent with previous evidence suggesting that some adolescent exposures could influence future breast cancer risk.

Adolescent↗
PubMed2000

Menstrual risk factors and early-onset breast cancer.

OBJECTIVES: Epidemiologic studies provide evidence for increased breast cancer risk among women with prolonged exposure to endogenous estrogens and progesterone. Menstrual cycle characteristics, such as early menarche, rapid initiation of regular ovulatory cycles, short cycle length, and more days of flow, all potentially contribute to higher cumulative ovarian hormone exposure. METHODS: We assessed the associations between these characteristics and breast cancer risk in a population-based, case-control study of 1505 controls and 1647 newly diagnosed cases, all younger than 45 years of age. RESULTS: Compared to women with menarche at > or =15 years, we observed some increase in risk for women with younger ages at menarche, although those with very early ages were not at particularly high risk [odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-1.9 for menarche at age 12 and OR = 1.2, 95% CI = 0.9-1.7 for menarche at age < or =10]. Women who reported having regular menstrual cycles within 2 years of menarche were at increased breast cancer risk (OR = 1.7, 95% CI = 1.2-2.3), compared to those never having regular cycles. Stratification by current body mass index revealed slightly stronger associations with menstrual characteristics among thinner women (< 22.0 kg/m2) compared to heavier women (> 28.8 kg/m2). CONCLUSIONS: These findings suggest that future studies should focus on clarifying how the interrelated effects of body size and menstrual factors, such as age at menarche and cycle regularity, contribute to breast cancer etiology.

Adolescent↗
PubMed2000

Alcohol consumption and breast cancer among black and white women in North Carolina (United States).

OBJECTIVE: The purpose of this study was to investigate the effects of alcohol consumption on breast cancer risk in black and white women. METHODS: We used data from the Carolina Breast Cancer Study, a population-based, case-control study of black and white women in North Carolina. Interviews were conducted with 890 cases and 841 controls frequency-matched on age and race. RESULTS: Overall, the prevalence of moderate to high levels of alcohol consumption was low. Compared with abstainers, the multivariate odds ratio for recent intake of one or two drinks per day was 1.4 (95% CI = 0.9-2.1) and two or more drinks a day was 1.0 (95% CI = 0.6-1.6); increasing consumption was not associated with risk (p for trend = 0.6). The associations were similar, but somewhat weaker, for average lifetime consumption. Among women who consumed 91 g/week or more of alcohol, a nonsignificant increased risk of breast cancer was observed for women reporting binge drinking (OR = 1.5; 95% CI = 0.9-2.3), but not for those who consumed less than 91 g/week reporting binge drinking (OR = 1.0; 95% CI = 0.6-1.5). Odds ratios did not differ meaningfully by race, age, menopausal status, exogenous hormone use, or body mass index. CONCLUSIONS: These data provide little evidence for an association between alcohol consumption and risk of breast cancer among either black or white women.

Adult↗
PubMed2000

Menopausal hormones and breast cancer in a biracial population.

OBJECTIVES: This study examined the association between menopausal hormones and breast cancer in a biracial population. METHODS: Logistic regression was used to calculate odds ratios for breast cancer associated with hormone use among 397 cases and 425 controls, all menopausal women. RESULTS: Odds ratios for ever use of hormones were 0.8 (95% confidence interval [CI] = 0.5, 1.2) for White women and 0.7 (95% CI = 0.4, 1.2) for Black women. Risk was not increased with longer duration of use or more recent use. CONCLUSIONS: Breast cancer risk was not increased among White or Black women who used menopausal hormones, despite patterns of use varying considerably between races.

Adult↗
PubMed2000

Risk of breast cancer according to the status of HER-2/neu oncogene amplification.

We examined risk factors for breast cancer after subdividing cases based on the presence of HER-2/neu oncogene amplification in their tumors. Data were from the Carolina Breast Cancer Study, a population-based, case-control study of 577 invasive breast cancer patients, diagnosed during 1993-1996 and ages 20-74 years, and 790 controls frequency-matched on race and age. Information on breast cancer risk factors was obtained from structured personal interviews. About 20% of paraffin-embedded tissues from the breast cancers of cases were identified as positive for HER-2/neu amplification (HER-2/neu+) by differential PCR. Early age at menarche, higher waist:hip ratio, and family history of breast or ovarian cancer were associated with elevated odds ratios (ORs) for both HER-2/neu+ and HER-2/neu- breast cancers. Breastfeeding for at least 1 year was inversely associated with HER-2/neu+ breast cancer [OR, 0.3; 95% confidence interval (CI), 0.1-0.7] more so than HER-2/neu- breast cancer (OR, 0.8; 95% CI, 0.5-1.2). Most of the remaining risk factors had ORs around 1.0 for both HER-2/neu+ and HER-2/neu- breast cancers, although a few exhibited possible associations with one disease subtype in analyses stratified by menopausal status. These study results suggest that most recognized breast cancer risk factors do not operate through HER-2/neu amplification in breast carcinogenesis. Differential effects of long-term breastfeeding by HER-2/neu amplification status have been observed in earlier studies and are provocative; however, the direction and magnitude of the associations have not been consistent.

Adult↗
PubMed2000

Glutathione S-transferases M1, T1, and P1 and breast cancer.

We examined associations for glutathione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) genotypes and breast cancer in the Carolina Breast Cancer Study, a population-based, case-control study in North Carolina. Odds ratios were close to the null value for each GST locus among African-American women (278 cases and 271 controls) and white women (410 cases and 392 controls), as well as pre- and postmenopausal women. For women with a history of breast cancer in one or more first-degree relatives, odds ratios were 2.1 (95% confidence interval, 1.0-4.2) for GSTM1 null and 1.9 (0.8-4.6) for GSTT1 null genotypes. Among women with a family history, age at diagnosis was significantly earlier for those with the GSTM1 null genotype. We did not observe strong evidence for modification of odds ratios for smoking according to GST genotypes. There was no evidence for combined effects of GSTM1, GSTT1, and GSTP1 genotypes, and there were no combined effects for GST genotypes and the catechol O-methyltransferase genotype. We conclude that GSTM1, GSTT1, and GSTP1 genotypes do not play a strong role in susceptibility to breast cancer. However, the role of GST genotypes in age at onset and risk of breast cancer among women with a family history merits further investigation.

Adult↗
PubMed1999

Exploring the role of environmental factors in association and linkage studies.

We analyzed some simulated data to assess the success of statistical methodologies to establish the role of the environmental factors (EF) and to identify associated and linked markers. We considered five replicates for each of the four studies, and, with the knowledge of the generating model, concentrated our analyses on chromosomes (CH) 1, 3, and 5. To determine the influence of EF and associated markers on the affection status (AS), we utilized chi-square tests for independence and recursive partitioning (via the CART software). To identify linked markers, we scanned the relevant chromosomes with nonparametric multipoint linkage (NPL) and transmission/disequilibrium tests. These analyses were performed on the whole data set as well as on subsets of individuals and families defined by exposure to EF. CART correctly selected the associated marker (D1G024) and EF1 for Study (ST) 1 and did not generate trees for the other studies. NPL identified the relevant regions on CH3 and CH5 but failed to do so for CH1, except in ST4. Stratifying families by exposure to EF1 did not consistently increase sensitivity of NPL to the relevant CH3 markers, but did help characterize the genetic heterogeneity and identify linked families.

Chi-Square Distribution↗
PubMed1999

P57 (KIP2) polymorphisms and breast cancer risk.

A previous report in this journal has suggested that germline deletions in the proline-alanine-rich (PAPA-repeat) region of P57 (KIP2) are associated with increased risk of a variety of cancers, including breast cancer. We have analyzed the association of P57 PAPA-repeat deletion polymorphisms and breast cancer risk as part of a population-based case-control study of breast cancer. We have not observed an association between the presence of one or two copies of deletion polymorphisms in P57 and breast cancer risk (adjusted odds ratio: 1.1, 95% confidence interval: 0.6-2.0). Further investigation is necessary to determine the functional significance of P57 deletion polymorphisms and their potential relationship with disease.

Breast Neoplasms↗
PubMed1999

Imaging of medical disease of the newborn lung.

Surfactant deficiency remains the most common and serious pulmonary affliction of premature infants. Exogenous surfactant and corticosteroid administration have had a major impact in improving survival and morbidity in this disease with consequent alterations in the clinical and radiographic course. Chronic lung disease, although still common, is usually less severe than previously, especially in larger infants. Significant therapeutic strides in treating persistent pulmonary hypertension with or without meconium aspiration have been the use of high-frequency ventilators, inhaled nitric oxide, and ECMO. Prompt recognition and treatment of infection, atelectasis, and air leak whether primary or secondary are important to overall outcome. Less common pulmonary conditions, such as lymphangiectasia, pulmonary hypoplasia, and alveolar proteinosis, may initially masquerade as more common lesions. Persistent pulmonary hypertension is often the initial diagnosis and part of the clinical problem. Attention must be paid to the clinical and radiographic appearance and excursion of the thoracic cage because deformities and malformations may be the cause of respiratory problems.

Humans↗
PubMed1999

Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility.

In order to evaluate the role of inherited variation in the estrogen receptor (ESR1) gene in human breast cancer, we determined intronic sequences flanking each ESRI exon; identified multiple SNPs and length polymorphisms in the ESR1 coding sequence, splice junctions and regulatory regions; and genotyped families at high risk of breast cancer and population-based breast cancer patients and controls. Of 10 polymorphic sites in ESR1, four are synonymous SNPs, two are nonsynonymous SNPs and four are length polymorphisms; five are novel. No ESR1 polymorphisms were associated with breast cancer, either in the high-risk families or the case-control study. We therefore conclude that inherited genetic variation is not a mechanism by which the estrogen receptor is commonly involved in breast cancer development.

5' Untranslated Regions↗
PubMed1999

Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy.

Proximal myotonic myopathy is a recently described autosomal dominant condition characterized by proximal myopathy, cataracts, intermittent myotonia, and myalgia. We report a further family with this condition. The proband and her two sisters presented with myotonia during pregnancy which resolved after each delivery. Two sisters experienced myalgia between each pregnancy. This relationship between pregnancy and symptom exacerbation suggests an intriguing hormonal influence in PROMM.

Adult↗
PubMed1999

Participation rates in a case-control study: the impact of age, race, and race of interviewer.

PURPOSE: Despite concerns about declining participation rates in epidemiologic studies in recent years, relatively few papers have discussed obstacles to recruiting study participants or strategies for optimizing response rates. This report describes factors associated with nonparticipation in a population-based, case-control study of breast cancer and discusses ways to overcome barriers to participation. METHODS: Contact and cooperation rates were calculated for participants in the Carolina Breast Cancer Study (CBCS), stratified by case status, age, race, and race of interviewer. Demographic and breast cancer risk factor characteristics of partial and full responders also were compared. RESULTS: Contact rates and cooperation rates varied by case/control status and demographic characteristics. Contact rates were lower among controls, younger women, and black women. Cooperation rates were lower among controls, older women, and black cases. Cooperation rates were higher among both black and nonblack women when participants and interviewers were concordant on race. CONCLUSIONS: Obstacles to recruitment seem to differ among race and age subgroups, suggesting that recruitment strategies may need to be tailored to potential participants based upon demographic characteristics. Strategies have been implemented to improve response rates in this and other epidemiologic studies; however, additional research and innovation in this area are needed.

Adult↗
PubMed1999

Women, employment status, and hypertension: cross-sectional and prospective findings from the Atherosclerosis Risk in Communities (ARIC) Study.

PURPOSE: This study examined the cross-sectional and prospective associations between employment status and hypertension among middle-aged, African-American (AA) and European-American (EA) women participating in the Atherosclerosis Risk in Communities Study. METHODS: Employed women and homemakers from the baseline examination (1987-89) were included in the cross-sectional study (n = 7351). Associations between employment and the incidence of hypertension ascertained at visit 2 (1990-92) were determined among those who at baseline, had low-normal blood pressure (not hypertensive and systolic blood pressure (SBP) < or = 120 mm Hg systolic and diastolic blood pressure (DBP) < or =80 mm Hg (n = 3194). Logistic regression analysis was used to examine the association between employment status and hypertension by ethnicity, taking into account covariates. RESULTS: At baseline, employed women were less likely to be hypertensive (SBP > or =140 mm Hg or DBP > or =90 mm Hg or current use of antihypertensive drugs) than were homemakers (prevalence odds ratio) (POR) = 0.70; 95% confidence interval (CI) = 0.62-0.79), controlling for age, body mass index, and education. Among the subgroup who had low-normal blood pressure at baseline, employed women were less likely to develop hypertension during the three-year time period than were homemakers (odds ratio (OR) = 0.68; 95% CI = 0.44-1.05). The inverse association was stronger among AA (RR = 0.37; 95% CI = 0.16-0.88) than EA (OR = 0.83; 95% CI = 0.50-1.38) women. CONCLUSIONS: These findings suggest that the inverse association between hypertension and employment status is not due to a healthy worker effect, and that employment may confer protection against incident hypertension in women.

Black or African American↗