The relationship of body mass index to reproductive factors in pre- and postmenopausal African-American women with and without breast cancer.

To date, there are virtually no existing data on the relationship between obesity, menopausal status, and breast cancer in African-Americans. Therefore, the present study was designed to test the following hypotheses in an African-American population: (1) there exists a positive association between BMI and breast cancer among postmenopausal women; (2) there exists an inverse association between BMI and breast cancer among premenopausal women; and (3) similar associations between BMI and reproductive factors exist for both pre- and postmenopausal breast cancer cases. The study population comprised 357 African-American women (n = 193 breast cancer cases; n = 164 controls). No significant differences were observed between premenopausal cases and controls for BMI, obesity categories, and reproductive factors. Among the postmenopausal women, the cases had significantly lower weight and BMI levels than the controls. Age at first pregnancy and parity were significantly lower among postmenopausal cases than their controls. No significant associations were revealed between body mass index and breast cancer for pre- and postmenopausal women. In the present study, early age at menarche was the only reproductive factor that was an independent predictor of BMI for both pre- and postmenopausal women, irrespective of breast cancer status. Also, these findings strongly suggest the need to consider reproductive factors, particularly age at menarche, as a covariate of BMI and other obesity-related diseases.

The impact of health insurance on an African-American population with colorectal cancer.

This study evaluates the impact of health insurance as a substitute for social class on tumor location, presentation, stage, grade, and age-adjusted survival in an African-American population. Patients were stratified by insurance into two groups: group 1 (private insurance and Medicare parts A & B) and group 2 (Medicaid, Medical Charity, self-pay, uninsured, or unemployed). A total of 212 patients were evaluated. Of these, 210 patients were insured or had Medical Charity, and two were uninsured. The type of health insurance did not significantly affect age-adjusted survival. However, age and stage at presentation were positive predictors of age-adjusted survival. Higher socioeconomic status was associated with group 1 health insurance.

Linkage between the APOB gene and serum ApoB levels in a large pedigree from the Bogalusa Heart Study.

Maximum likelihood linkage analyses were performed to test for linkage between serum apoB levels and several candidate gene markers including apolipoprotein B, lipoprotein lipase, hepatic lipase, cholesterol ester transfer protein, and apolipoprotein AI in a large pedigree. Parameters of general Mendelian inheritance derived from maximum likelihood segregation analysis of the serum apoB levels were used in the linkage analysis. The highest two-point lod score between the quantitative trait and a marker defined by a single restriction digest was 1.86 at recombination fraction (theta) = 0. This was observed for linkage between serum apoB levels and the presence or absence of a PvuII digestion site in the apoB gene. Linkage between serum apoB levels and polymorphisms of the apoB gene defined by the two restriction digests EcoR1 and PvuII was supported by a lod score of 3.30, while inclusion of VNTR typings led to a lod score of 2.33. None of the other candidate genes gave positive evidence of linkage.

Breast cancer risk factors in African-American women: the Howard University Tumor Registry experience.

This retrospective case-control study examines risk factors for breast cancer in African-American women, who recently have shown an increase in the incidence of this malignancy, especially in younger women. Our study involves 503 cases from the Howard University Hospital and 539 controls from the same hospital, seen from 1978 to 1987. Using information culled from medical charts, an analysis of various factors for their effect on breast cancer risk was made. The source of data necessarily meant that some known risk factors were missing. Increases in risk were found for known risk factors such as decreased age at menarche and a family history of breast cancer. No change in risk was observed with single marital status, nulliparity, premenopausal status, or lactation. An increased odds ratio was found for induced abortions, which was significant in women diagnosed after 50 years of age. Spontaneous abortions had a small but significant protective effect in the same subgroup of women. Birth control pill usage conferred a significantly increased risk. It is of note that abortions and oral contraceptive usage, not yet studied in African Americans, have been suggested as possibly contributing to the recent increase in breast cancer in young African-American women.

Descriptive analysis of breast cancer in African-American women at Howard University Hospital, 1960-1987.

This article describes breast cancer cases seen at the Howard University Hospital from 1960 through 1987 using information from the database of the Tumor Registry, established in 1960. Clinical information at presentation is presented as well as a description of reproductive and demographic characteristics. Pre- and postmenopausal women are compared, revealing differences in reproductive experience. This may contribute to the increasing incidence of breast cancer seen among younger women in recent years. This is of particular interest because the classic excess of nulliparous women among breast cancer cases is not seen among the population described here.

A comparison of univariate and multivariate tests for genetic linkage.

A variety of robust and model-dependent genetic linkage methods were applied to log transformed lipid levels from a large pedigree in which the LDL receptor defect has been shown to segregate by molecular biologic techniques. Application of the Haseman-Elston and a variance-components based test for linkage identified LDL and cholesterol as cosegregating with the marker C3, which is genetically linked to the LDL receptor defect. Consideration of lipid fractions as a multivariate response identified (0.723 x cholesterol) - (0.551 x triglycerides) as most strongly supporting evidence for linkage with C3. Subsequent segregation and linkage analyses provided support for an autosomal dominant major gene influencing either LDL or the function of cholesterol and triglycerides. Genetic linkage to LDL was only mildly supported, with a maximum lod score of 0.51 at a recombination fraction of theta = 0.33. Genetic linkage of the linear function to C3 was more strongly supported, with a maximum lod score of 1.69 at theta = 0.09. Bivariate analysis of clinical affection (with either type IIa or type IIb hyperlipidemia) and quantitative measures (LDL or the linear function) generally led to decreased lod scores, indicating, in this pedigree, loss of information when using clinical affection.

Numerical comparisons of two formulations of the logistic regressive models with the mixed model in segregation analysis of discrete traits.

Segregation analysis of discrete traits can be conducted by the classical mixed model and the recently introduced regressive models. The mixed model assumes an underlying liability to the disease, to which a major gene, a multifactorial component, and random environment contribute independently. Affected persons have a liability exceeding a threshold. The regressive logistic models assume that the logarithm of the odds of being affected is a linear function of major genotype effects, the phenotypes of older relatives, and other covariates. A formulation of the regressive models, based on an underlying liability model, has been recently proposed. The regression coefficients on antecedents are expressed in terms of the relevant familial correlations and a one-to-one correspondence with the parameters of the mixed model can thus be established. Computer simulations are conducted to evaluate the fit of the two formulations of the regressive models to the mixed model on nuclear families. The two forms of the class D regressive model provide a good fit to a generated mixed model, in terms of both hypothesis testing and parameter estimation. The simpler class A regressive model, which assumes that the outcomes of children depend solely on the outcomes of parents, is not robust against a sib-sib correlation exceeding that specified by the model, emphasizing testing class A against class D. The studies reported here show that if the true state of nature is that described by the mixed model, then a regressive model will do just as well. Moreover, the regressive models, allowing for more patterns of family dependence, provide a flexible framework to understand gene-environment interactions in complex diseases.

The effects of oestrogen administration on tryptophan metabolism in rats and in menopausal women receiving hormone replacement therapy.

The effects of the administration of oestrogens on the activity of hepatic tryptophan oxygenase have been assessed both directly (by measurement of enzyme activity in vitro) and indirectly (by measurement of urinary excretion of tryptophan metabolites) in rats, and indirectly in menopausal women receiving hormone replacement therapy. Intraperitoneal administration of 500 micrograms of oestradiol or ethinyl oestradiol/kg body wt had no effect on the activity of tryptophan oxygenase in homogenates of liver from mature (13-week-old) female rats. Both adrenalectomy and ovariectomy led to a reduction in the activity of tryptophan oxygenase in homogenates of liver from mature rats; again there was no effect of giving 500 micrograms of oestradiol/kg body wt by intraperitoneal injection. Intraperitoneal administration of 210 micrograms of oestrone sulphate/kg body wt for 1 or 2 days before killing, or its incorporation in the diet for up to 8 weeks at an equivalent dose rate, had no effect on the activity of tryptophan oxygenase in homogenates of liver from ovariectomized 6-14-week-old female rats. Intraperitoneal administration of 500 micrograms oestradiol/kg body wt to intact mature female rats together with 500 mg tryptophan/kg body wt caused a reduction in the urinary excretion of xanthurenic and kynurenic acids, kynurenine and N1-methyl nicotinamide. When peri- and post-menopausal women were treated with ethinyl oestradiol (20 micrograms/day) or piperazine oestrone sulphate (3 mg/day) for 3 months, there was an increase in the concn of tryptophan in plasma, with no change in the urinary excretion of xanthurenic and kynurenic acids and kynurenine. This study provides no evidence for the induction of tryptophan oxygenase by oestrogens in rats or human beings.