Obesity is associated with atypia in breast ductal lavage of women with proliferative breast disease.

BACKGROUND: Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. METHODS: We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. RESULTS: There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index was also significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. CONCLUSIONS: Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk.

5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children.

BACKGROUND: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism. Polymorphisms at the C677T and A1298C loci are associated with reduced activity; consequently more folate substrates are shunted toward thymidylate and DNA synthesis. Several studies have reported a reduced risk of developing ALL in children with MTHFR polymorphisms. The objective of this study was to determine the association between MTHFR polymorphisms and ALL in Filipino children. PROCEDURE: We conducted a case control study in children diagnosed with ALL at the Philippine General Hospital from 1/2001 through 12/2005. Bone marrow aspirate slides were reviewed by two expert hematologists to verify the morphologic diagnosis of ALL. DNA was isolated from the slides and MTHFR polymorphisms, C677T and A1298C, were determined using Taqman real-time PCR. Cord blood of healthy Filipino newborns served as control. RESULTS: There were a total of 191 ALL and 394 controls genotyped. The distribution of C677T polymorphisms was similar in the two groups (P = 1.0). However, for A1298C, there was significantly more AC and CC genotypes in the ALL compared to controls (P = 0.02; OR 1.57; CI: 1.08-2.28). The 1298C allele frequency for the control group was 36.8% and 677T allele frequency was 9.9%. CONCLUSION: A1298C polymorphisms is associated with an increased risk for ALL in Filipino children. This may be due to a difference in leukemia biology or to a high prevalence of folate deficiency in Filipinos. Our study reiterates the gene and environment interaction in leukemogenesis.

Quality of life as a predictor of weight loss in obese, early-stage breast cancer survivors.

PURPOSE/OBJECTIVES: To investigate whether quality of life (QOL) assessed before weight loss intervention predicts weight loss and, in turn, what the effect of weight loss is on QOL measures after 12 months in early-stage breast cancer survivors. DESIGN: A clinical trial of a weight loss intervention in breast cancer survivors. SETTING: Community-wide recruitment in Detroit, MI. SAMPLE: 39 breast cancer survivors (body mass index = 30-44 kg/m2), within three years of initial diagnosis and at least three months after chemotherapy or radiation therapy. METHODS: Participants were randomized to one of three weight loss methods or a control group. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) QOL questionnaire was administered at baseline and after the intervention. MAIN RESEARCH VARIABLES: Six subscales of the FACT-An and weight change. FINDINGS: Modest but statistically significant associations were found for the physical and functional subscales of the FACT-An with weight loss for 39 subjects who completed 12 months of the study. Those reporting relatively impaired physical or functional QOL at baseline lost more weight, which accounted for 8%-9% of the weight loss variance beyond that resulting from the diet arm assignment. At 12 months, greater weight loss was associated with significant improvements in overall FACT-An score and in the physical, functional, fatigue, and anemia subscales (p < 0.05). CONCLUSIONS: Relatively low physical function at baseline was not a barrier to weight loss; indeed, it may have been a motivating factor in adherence to the weight loss intervention. Weight loss was associated with improvement in several QOL subscale measures in breast cancer survivors, but the emotional and social subscales were not affected. IMPLICATIONS FOR NURSING: Counseling for weight loss that includes recommendations for exercise should not be withheld for patients with relatively low physical functioning.

Genetic determinants of bone mass do not relate with breast cancer risk in US white and African-American women.

INTRODUCTION: The association between high bone mass and increased breast cancer risk has been established. Identification of polymorphisms and the resultant variant receptors suggests the possibility of differential effects on hormone responsive genes when complexed with the hormones. Both estrogen receptor-alpha (ER) and vitamin D receptor (VDR) polymorphisms have been associated with bone density. Thus, we examined these polymorphisms for association with increased breast cancer risk among US African-American and white women. METHODS: A case-control study was conducted to measure ER and VDR polymorphisms and radial bone mineral density (BMD) in African-American and white women, and to examine the association between polymorphisms, bone density and breast cancer risk. Genotypes and bone density were obtained from 412 women (220 cases and 192 controls, with equal distribution between the two ethnic groups). RESULTS: We found no evidence for an association between either the ER or VDR genotypes and breast cancer risk. Also, there was no difference in the risk of breast cancer by genotypes after adjusting for ethnicity. The addition of age, sex and ethnicity-specific BMD (Z-scores) did not significantly change the odds ratio for breast cancer. CONCLUSIONS: Our data suggest that the polymorphisms investigated had no effect on risk of breast cancer in this population. Thus, we found no evidence to support our hypothesis that breast cancer cases and controls would have a different distribution of ER and VDR genotypes. Furthermore, the polymorphisms were not associated with differences in bone mass and its relationship with breast cancer risk.

Impact of a genetic variant in CYP3A4 on risk and clinical presentation of prostate cancer among white and African-American men.

Genes involved in androgen metabolism are strong candidates for having an important role in the pathogenesis of prostate cancer. CYP3A4, a protein in the cytochrome P-450 supergene family, facilitates the oxidative deactivation of testosterone. In previous studies, patients with the G variant of a genetic polymorphism in CYP3A4 had prostate cancers with clinically aggressive characteristics at diagnosis. The association was strongest among elderly men. We investigated whether the CYP3A4 variant was linked with the diagnosis or clinical presentation of prostate cancer in a case control study of a multiethnic urban population. Biologic specimens were genotyped for CYP3A4, and analyzed for the impact of this genotype on risk and tumor characteristics at presentation, controlling for the effect of several cofactors. The CYP3A4 variant was more common among African-Americans than among white men. Race-stratified analyses revealed little association between the CYP3A4 variant and prostate cancer risk among white men but were limited by the small number of white men with the CYP3A4 variant. Of African-American men, while the variant G allele was not associated with prostate cancer that had less aggressive characteristics, it was associated with risk of aggressive prostate cancer when men with the AG genotype (odds ratio = 9.3, 95% confidence interval 1.3-411) or GG genotype (odds ratio = 11.9 95% confidence interval 1.6-533) were compared with those with the AA genotype. The association between the CYP3A4 genotype and aggressive prostate cancer in African-American men is consistent with findings of other studies.

The relationship between blood leptin level and bone density is specific to ethnicity and menopausal status.

Leptin, the obesity hormone, has been linked to bone mineralization and tumorigenesis. In addition, both bone mineral density (BMD) and postmenopausal breast cancer are associated with obesity, but the interrelationships between obesity, leptin, BMD, and breast cancer are not yet clear. In particular, there is little published research comparing white and black women in terms of these variables. We obtained blood specimens for leptin analysis from a group of 320 breast cancer patients and controls with an ethnic composition of 49% white women and 51% black women. Distal and proximal radial BMD (DBMD and PBMD) were measured by dual-energy X-ray absorptiometry, and age- and ethnicity-specific standardized scores (Z-scores) were calculated for bone density. Blood leptin levels were determined by radioimmunoassay. Blood leptin level was not linked to breast cancer risk. Leptin levels were significantly higher in black women than in white women and were also significantly higher in obese and overweight women than in normal-weight women. Black women weighed more and had a higher body mass index (BMI) than white women. After controlling for BMI, leptin was correlated with DBMD ( r = .17; P < .05) and PBMD ( r = .21; P < .05) in whites, but not in blacks. Leptin was also correlated with both distal and proximal Z-scores in postmenopausal women ( r = .14 and .13; P < .05). Thus leptin may be a predictor for BMD in a population that is prone to have a low BMD, and this relationship is independent of the effect of body weight on leptin levels. Our results suggest that ethnicity and menopausal status should be considered when comparing results from different studies.

Relationship of psychiatric diagnosis and weight loss maintenance in obese breast cancer survivors.

OBJECTIVE: Obese breast cancer survivors are a unique population for weight loss counseling because both obesity and a diagnosis of breast cancer can increase the risk of depression. In this pilot study, weight loss maintenance was examined in obese breast cancer survivors with relationship to psychiatric diagnosis. RESEARCH METHODS AND PROCEDURES: Forty-eight subjects were enrolled. The intervention, which used individualized counseling for diet and exercise, lasted 24 months. After a 6-month period of no contact with study subjects, a follow-up body weight was obtained at 30 months. RESULTS: The nine subjects who dropped out of the study before 12 months all failed to complete a structured psychiatric interview. Of the remaining 39 subjects, 9 had major depressive disorder, and 10 had a definable psychiatric disorder of lesser severity such as adjustment disorder. Subjects with any type of psychiatric diagnosis displayed significantly less weight loss at the 12-month time-point than those with no diagnosis (6.3% vs. 12.6% loss of baseline weight, respectively). At the 30-month follow-up visit, subjects with any psychiatric disorder had a mean weight loss of 1.2% of baseline weight compared with 7.8% weight loss in subjects with no diagnosis. DISCUSSION: These results suggest that the presence of psychiatric disorders can interfere with weight loss. Therefore, recognition and treatment of psychiatric disorders may be important in attempts at weight reduction, and this will be especially important in populations such as cancer survivors, who seem to have higher rates of depression and other disorders than the general population.

Combining weight-loss counseling with the weight watchers plan for obese breast cancer survivors.

OBJECTIVE: The objective was to develop effective weight-loss methods for women who have had breast cancer, because obesity may result in an adverse prognosis. RESEARCH METHODS AND PROCEDURES: This randomized pilot study tested an individualized approach toward weight loss in obese women who have had a diagnosis of breast cancer. An individualized approach was applied either alone or combined with the commercial Weight Watchers program. Forty-eight women (body mass index of 30 to 44 kg/m(2)) were enrolled. RESULTS: Weight change after 12 months of intervention was as follows (mean +/- SD): 0.85 +/- 6.0 kg in the control group, -2.6 +/- 5.9 kg in the Weight Watchers group, -8.0 +/- 5.5 kg in the individualized group, and -9.4 +/- 8.6 kg in the comprehensive group that used both individualized counseling and Weight Watchers. Weight loss relative to control was statistically significant in the comprehensive group 3, 6, and 12 months after randomization, whereas weight loss in the individualized group was significant only at 12 months. Weight loss of 10% or more of initial body weight was observed in 6 of 10 women in the comprehensive group at 12 months. In the comprehensive and Weight Watchers-only groups, weight loss was significantly related to frequency of attendance at Weight Watchers meetings, and attendance was more frequent in the comprehensive group. DISCUSSION: These data indicate that the most weight loss was achieved when the counseling approach combined both Weight Watchers and individualized contacts. This was effective even though most of the individualized contacts were by telephone.

A Study of the Efficacy and Safety of Moexipril in Mild to Moderate Hypertension.

This placebo-controlled, double-blind, multicenter study examined the efficacy, safety, and tolerability of the angiotensin-converting enzyme inhibitor, moexipril, in lowering blood pressure in mildly to moderately hypertensive patients. Patients were initially randomized into four groups, two of which received moexipril 7.5 mg per day and two received moexipril 15 mg per day, for first 12 weeks of treatment. Patients then entered a withdrawal phase with one of the groups in each dose category continuing that dose of moexipril and one receiving placebo for 12 more weeks. From 223 patients randomized initially, 190 completed the 12-week withdrawal phase. In the two dosage groups from baseline to 12 weeks, sitting diastolic blood pressure decreased from 101.1 to 92.8 mm Hg for the 7.5-mg group and from 100.7 to 91.3 mm Hg for the 15-mg group (p < 0.05 baseline to week 12 in both groups) with a significant difference between those groups attained at week 12 only (p = 0.03). By the end of the withdrawal phase (24-week evaluation), the group that continued to receive 7.5 mg moexipril decreased diastolic blood pressure by 8.2 mm Hg, whereas the corresponding placebo group decreased diastolic blood pressure by 3.7 mm Hg. Although the difference between these two groups was not significant at the 24-week end point, all other time points differed significantly between groups at p less-than-or-equal 0.017. Similarly, whereas the corresponding placebo group had a mean reduction in diastolic blood pressure of 4.6 mm Hg, the group that continued 15 mg of moexipril showed a mean diastolic blood pressure reduction of 10.6 mm Hg (p < 0.001 between groups). No comparison between the two moexipril dosage groups was significant, however, during the withdrawal phase. These results during medication withdrawal indicate that moexipril is effective in significantly lowering diastolic blood pressure.