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1.
Maturitas ; 38(1): 103-13; discussion 113-6, 2001 Feb 28.
Article in English | MEDLINE | ID: mdl-11311599

ABSTRACT

UNLABELLED: In North America and Northern Europe, breast cancer incidence rates begin increasing in the early reproductive years and continue climbing into the late seventies, whereas rates plateau after menopause in japan and less developed countries. Female gender, age and country of birth are the strongest determinants of disease risk. Family history and mutations in the BRCA1 and BRCA2 genes are important correlates of lifetime risk. Genetic polymorphisms associated with estrogen synthesis and metabolism are currently under study. Atypical hyperplasia and molecular alterations in benign breast lesions appear to be involved in the pathogenesis of invasive carcinoma. In postmenopausal women, increased breast density on mammograms increases risk. Bone density and breast cancer are associated, presumably through the mechanism of endogenous estrogen levels. Serum estrogen levels are higher in breast cancer cases than controls. Many established risk factors for breast cancer may function through and endocrine mechanism. Current use of oral contraceptives and prolonged, current or recent use of hormone replacement therapy moderately increase risk. Tamoxifen and possibly other selective estrogen receptor modulators reduce breast cancer risk in high risk women. Relationships between various dietary micro and macronutrients and breast cancer have been suggested but require evaluation in clinical trials. Whereas alcohol consumption is associated with increased risk, most environmental factors, including polychlorinated compounds and electromagnetic fields, are not. CONCLUSION: Breast cancer etiology is becoming clearer through the study of molecular alterations in germline and somatic cell genes, and the interaction of these genes with steroid hormones and relevant growth factors. This knowledge should be useful for breast cancer prevention.


Subject(s)
Breast Neoplasms/etiology , Hormones , Breast Neoplasms/genetics , Estrogen Receptor Modulators , Female , Hormone Replacement Therapy , Humans , Risk Factors
2.
N Engl J Med ; 342(11): 781-90, 2000 Mar 16.
Article in English | MEDLINE | ID: mdl-10717013

ABSTRACT

BACKGROUND: The postulated relation between silicone breast implants and the risk of connective-tissue and autoimmune diseases has generated intense medical and legal interest during the past decade. The salience of the issue persists, despite the fact that a great deal of research has been conducted on this subject. To provide a stronger quantitative basis for addressing the postulated relation, we applied several techniques of meta-analysis that combine, compare, and summarize the results of existing relevant studies. METHODS: We searched data bases and reviewed citations in relevant articles to identify studies that met prestated inclusion criteria. Nine cohort studies, nine case-control studies, and two cross-sectional studies were included in our meta-analyses. We conducted meta-analyses of the results of these studies, both with and without adjustment for confounding factors, and a separate analysis restricted to studies of silicone-gel-filled breast implants. Finally, we estimated the annual number of new cases of connective-tissue disease that could be attributed to breast implants. RESULTS: There was no evidence that breast implants were associated with a significant increase in the summary adjusted relative risk of individual connective-tissue diseases (rheumatoid arthritis, 1.04 [95 percent confidence interval, 0.72 to 1.51]; systemic lupus erythematosus, 0.65 [95 percent confidence interval, 0.35 to 1.23]; scleroderma or systemic sclerosis, 1.01 [95 percent confidence interval, 0.59 to 1.73]; and Sjögren's syndrome, 1.42 [95 percent confidence interval, 0.65 to 3.11]); all definite connective-tissue diseases combined (0.80; 95 percent confidence interval, 0.62 to 1.04); or other autoimmune or rheumatic conditions (0.96; 95 percent confidence interval, 0.74 to 1.25). Nor was there evidence of significantly increased risk in the unadjusted analyses or in the analysis restricted to silicone-gel-filled implants. CONCLUSIONS: On the basis of our meta-analyses, there was no evidence of an association between breast implants in general, or silicone-gel-filled breast implants specifically, and any of the individual connective-tissue diseases, all definite connective-tissue diseases combined, or other autoimmune or rheumatic conditions. From a public health perspective, breast implants appear to have a minimal effect on the number of women in whom connective-tissue diseases develop, and the elimination of implants would not be likely to reduce the incidence of connective-tissue diseases.


Subject(s)
Breast Implants/adverse effects , Connective Tissue Diseases/etiology , Silicone Gels/adverse effects , Autoimmune Diseases/etiology , Case-Control Studies , Cohort Studies , Confounding Factors, Epidemiologic , Cross-Sectional Studies , Female , Humans , Odds Ratio , Rheumatic Diseases/etiology , Risk
4.
Cancer Epidemiol Biomarkers Prev ; 9(1): 65-71, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10667465

ABSTRACT

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.


Subject(s)
Breast Neoplasms/etiology , Gene Amplification/genetics , Genes, erbB-2/genetics , Receptor, ErbB-2/genetics , Adult , Age Factors , Aged , Body Constitution , Breast Feeding , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Case-Control Studies , Confidence Intervals , Female , Humans , Interviews as Topic , Menarche , Menopause , Middle Aged , Neoplasm Invasiveness , Odds Ratio , Ovarian Neoplasms/genetics , Paraffin Embedding , Population Surveillance , Risk Factors
5.
J Clin Oncol ; 18(2): 267-74, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10637239

ABSTRACT

PURPOSE: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. PATIENTS AND METHODS: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. RESULTS: Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio ¿OR = 2.2; 95% confidence interval ¿CI, 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P =.06, Fisher's exact test). CONCLUSION: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.


Subject(s)
Breast Diseases/genetics , Breast Neoplasms/genetics , Gene Amplification , Receptor, ErbB-2/genetics , Adult , Breast Diseases/pathology , Breast Neoplasms/etiology , Breast Neoplasms/pathology , Case-Control Studies , Female , Gene Expression Regulation, Neoplastic , Humans , Receptor, ErbB-2/biosynthesis , Risk Assessment
6.
Am J Epidemiol ; 151(7): 703-14, 2000 Apr 01.
Article in English | MEDLINE | ID: mdl-10752798

ABSTRACT

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.


Subject(s)
Breast Neoplasms/chemistry , Breast Neoplasms/etiology , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Adult , Aged , Breast Neoplasms/epidemiology , Case-Control Studies , Female , Humans , Middle Aged , North Carolina/epidemiology , Odds Ratio , Pregnancy , Risk , Risk Factors
7.
Public Health Nutr ; 2(3): 283-91, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10512563

ABSTRACT

OBJECTIVE: To determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer. DESIGN: This was a clinic-based case-control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing. SETTING: University-based breast referral clinics. SUBJECTS: One hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls. RESULTS: There were significant mean differences in 1,25-D levels (pmol ml(-1)) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference +/-SE: -11.08+/-0.76), and black cases had higher 1.25-D levels than black controls (mean difference +/-SE: 4.54+/-2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case-control differences in 25-D levels in either group. CONCLUSIONS: These data are consistent with a protective effect of 1,25-D for breast cancer in white women.


Subject(s)
Adenocarcinoma/blood , Breast Neoplasms/blood , Vitamin D/analogs & derivatives , Adult , Analysis of Variance , Case-Control Studies , Female , Humans , Logistic Models , Odds Ratio , Radioimmunoassay , Risk Factors , Vitamin D/blood
8.
Am J Epidemiol ; 148(8): 719-27, 1998 Oct 15.
Article in English | MEDLINE | ID: mdl-9786226

ABSTRACT

High maternal serum alpha-fetoprotein (AFP) levels during pregnancy may be instrumental in reducing the subsequent risk of breast cancer. This hypothesis was tested in a nested case-control study using stored frozen sera accrued between 1959 and 1966 by the University of California at Berkeley Child Health and Development Studies (CHDS) group from a cohort of pregnant women. Cases with histologically confirmed breast cancer were identified from California Cancer Registry files covering their date of enrollment in the CHDS until 1994. Controls were selected from the CHDS cohort by using randomized recruitment. Third-trimester maternal serum AFP levels were analyzed by using both a radioimmunoassay and an immunoenzymatic method. After controlling for multiple confounders in logistic regression models, the authors found an inverse association between high levels of maternal serum AFP (top quartile) during the index pregnancy and the risk of breast cancer. The protective effect of high levels of maternal serum AFP varied by age at first full-term pregnancy (age 20 years or less: odds ratio (OR) = 0.43, 95% confidence interval (CI) 0.28-0.65; age 21-23 years: OR = 0.62, 95% CI 0.41-0.92). After age 27 years, the estimated risk exceeded unity (OR = 1.67, 95% CI 1.14-2.45). These study findings suggest that some of the protection against breast cancer conferred by early first full-term pregnancy may result from high levels of maternal serum AFP. After age 27 years, a high maternal serum AFP level is not protective and may increase risk.


Subject(s)
Breast Neoplasms/blood , Pregnancy/blood , alpha-Fetoproteins/metabolism , Adolescent , Adult , Age Factors , Breast Neoplasms/epidemiology , California/epidemiology , Case-Control Studies , Female , Humans , Logistic Models , Odds Ratio , Risk
9.
Cancer Epidemiol Biomarkers Prev ; 7(6): 483-8, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9641492

ABSTRACT

A nested case-control study was conducted to investigate the hypothesis that women with high levels of high-density lipoprotein cholesterol (HDL-C) are at an increased risk of breast cancer. The source population was a cohort of 95,000 women enrolled in the Kaiser Permanente Medical Care Program who underwent a routine multiphasic health examination between 1964 and 1971. From the more than 2,000 breast cancer cases diagnosed in this cohort, 200 cases were randomly selected for this study. For each case, one control who matched on age and date of examination was chosen. Lipid and lipoprotein levels were measured in archived serum samples collected at the time of the women's examinations. Breast cancer risk factor information was obtained from questionnaires completed by the women when their blood was drawn and was supplemented with information from medical records. HDL-C levels were not significantly different between the cases and controls overall; however, a statistically significant interaction between the HDL-C level and menopausal status at diagnosis was detected. Premenopausal cases had mean HDL-C levels 3.48 mg/dl lower than matched controls [95% confidence interval (CI), -7.05, 0.09], whereas postmenopausal cases had levels 2.05 mg/dl higher than controls (95% CI, -0.94, 5.03). In multivariate conditional logistic regression analyses, the odds ratio associated with each 1 mg/dl increase in HDL-C was 0.96 (95% Cl, 0.93-1.0) for premenopausal women and 1.02 (95% CI, 0.99-1.05) for postmenopausal women. Although many breast cancer risk factors are associated with high HDL-C, the relationship between breast cancer and HDL-C was independent of other factors evaluated.


Subject(s)
Breast Neoplasms/blood , Cholesterol, HDL/blood , Menopause/blood , Adult , Aged , Case-Control Studies , Female , Humans , Middle Aged , Odds Ratio , Risk , Risk Factors , Surveys and Questionnaires
10.
Cancer Epidemiol Biomarkers Prev ; 6(11): 881-6, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9367060

ABSTRACT

In a retrospective cohort study of 262 premenopausal breast cancer patients treated at the Mayo Clinic between 1965 and 1985, we investigated whether survival was associated with the timing of tumor removal during the menstrual cycle. Participants were women < or = 50 years old who had not used exogenous hormones, been pregnant, been lactating, or given birth within 6 months of diagnosis. The menstrual cycle day at surgery was used to assign women to group 1 (cycle days 0-7), group 2 (cycle days 8-15), or group 3 (after cycle day 15). Cox proportional hazards analysis adjusting for age at diagnosis, stage, tumor size, grade, and node involvement showed a nonsignificantly worse survival for group 2 than for group 3 [hazard ratio (HR), 1.41; 95% confidence interval (CI), 0.89-2.23]. Stratification revealed that the association between survival and timing of tumor removal during the menstrual cycle was slightly stronger among patients with stage II disease (adjusted HR, 1.56; 95% CI, 0.92-2.63). The association was the same among patients with stage II disease and node involvement (adjusted HR, 1.57; 95% CI, 0.82-3.03). Prospective studies using hormone measurements to define menstrual cycle status more accurately than the reported day of the menstrual cycle could provide further insight about the postulated association.


Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/surgery , Mastectomy , Menstrual Cycle , Adult , Breast Neoplasms/pathology , Cohort Studies , Female , Humans , Lymphatic Metastasis , Middle Aged , Multivariate Analysis , Neoplasm Staging , Premenopause , Proportional Hazards Models , Retrospective Studies , Survival Analysis
11.
Prog Clin Biol Res ; 396: 17-29, 1997.
Article in English | MEDLINE | ID: mdl-9108587

ABSTRACT

This review focuses on etiologic factors and hormonal correlates of the three major gynecologic cancers-uterine cervix, uterine corpus and ovary- and breast cancer. The incidence rate of the three gynecologic cancers combined is only 40 percent of the breast cancer rate (43.6 vs 109.5 per 100,000), whereas the combined mortality rate is half that for breast cancer (14.3 vs 27.3 per 100,000). Cervical cancer is distinctive in that it's hormonal correlates are few; it exhibits the epidemiologic characteristics of a sexually transmitted disease. Integration of Human Papilloma Virus DNA types 16, 18 (or other) within the cellular genome has been identified in more than 80% of high grade cervical intraepithelial neoplasias and invasive carcinomas. Epithelial ovarian cancers occur most commonly in nulliparous, infertile women and familial carriers of BRCA1. Oral contraceptive (OC) use reduces ovarian cancer risk by at least one-half, a benefit which increases with increasing duration of use and persists for at least 15 years after discontinuation. Pregnancy and OCs suppress gonadotropin secretion, whereas fertility drugs enhance follicle-stimulating hormone production. These indicators of alterations in the hypothalmic-pituitary-ovarian axis provide some support for both the excess gonadotropin and the incessant ovulation theories of ovarian carcinogenesis. Endometrial carcinoma is the prototype hormonally-determined disease. Increased estrogen from either endogenous or exogenous sources increases risk. Lowering the estrogen load or adding progestin reduces risk. This explains the marked protection achieved by combined estrogen/progestin OC's and the dramatic increased risk uncurred by long-term estrogen replacement therapy (ERT). Breast tissue, also a target for sex steroid hormones, displays a more complex risk profile. Current ERT use increases breast cancer risk by about 30%; adding a progestin to the estrogen does not improve the situation (40% increased risk). Furthermore, OCs do not reduce breast cancer risk, but may increase it for current OC users under age 45. The magnitude of these hormonal effects is much smaller than that exhibited with endometrial cancer.


Subject(s)
Breast Neoplasms/epidemiology , Genital Neoplasms, Female/epidemiology , Breast Neoplasms, Male/epidemiology , Endometrial Neoplasms/epidemiology , Female , Humans , Incidence , Male , Ovarian Neoplasms/epidemiology , Risk Assessment , Uterine Cervical Neoplasms/epidemiology
12.
Cancer Res ; 56(20): 4773-7, 1996 Oct 15.
Article in English | MEDLINE | ID: mdl-8840997

ABSTRACT

In this report, we describe the sequence allelotyping of the Ha-ras variable number tandem repeat (VNTR) region using a minisatellite variant repeat (MVR)-PCR approach. This method permits the rapid identification of internal sequence variations among the VNTR alleles, exploiting the presence of two polymorphic sites within the 28-bp repeat subunits that give rise to four distinct repeat types. Using MVR-PCR, 20 to 25 repeats at the 5' end of the VNTR can be sequenced rapidly and reliably. MVR typing of the common alleles a1, a2, a3, and a4 shows that the first six repeats at the 5' end of each allele constitutes an invariant region. Beginning with repeat 7, characteristic "signature" MVR patterns emerge for each common allele. The a1 and a2 common alleles were found to consist of specific repeat types 1, 2, and 3, whereas a3 and a4 contain an additional repeat type 4 not present in the smaller alleles. MVR typing of rare-length alleles indicates that they are comprised of disorganized sequences, although they usually bear a resemblance to one of the common alleles at the 5'-most end. These results suggest that the rare alleles may be generated from recombination or gene conversion-type events involving the common progenitor alleles. MVR typing could, therefore, improve the ascertainment of rare Ha-ras alleles and may provide molecular insights into the genesis of cancer-associated alleles.


Subject(s)
Alleles , Genes, ras/genetics , Minisatellite Repeats/genetics , Heterozygote , Homozygote , Humans , Polymerase Chain Reaction/methods , Tumor Cells, Cultured , Urinary Bladder Neoplasms/genetics
14.
Prog Clin Biol Res ; 395: 159-74, 1996.
Article in English | MEDLINE | ID: mdl-8895988

ABSTRACT

Numerous factors have been noted to be associated with risk of breast cancer. Indicators of endogenous hormonal alterations are among them: early age at menarche and late age at menopause, nulliparity, late age at first full term pregnancy and obesity in postmenopausal women. Other established risk factors are family history of breast cancer, histologic characteristics of benign tissue, mammographic patterns, exogenous hormones and alcohol consumption. Endogenous indicators may be a reflection of enhanced susceptibility, whereas exogenous exposures can have both independent effects on risk and the ability to interact with markers of inherited susceptibility. In case control studies of breast cancer, family history confers a risk elevation of two to three fold. The higher risk estimate occurs when first degree rather than second degree relatives are affected, or if more than one relative is affected. A relative diagnosed before age 45 increases risk for early-onset breast cancer. These findings have been obtained using either traditional analytic methods for case control data or an alternative strategy, which uses case control status as the predictor variable and models the risk to relatives in a time-dependent fashion. Risk of breast cancer is greater for the mother and sisters of cases than controls. The magnitude of risk increases with 1) decreasing age of diagnosis of the index case 2) additional family members with diagnosed breast cancer and 3) bilateral breast cancer in the index case. Although these two analytic approaches have somewhat different data requirements and may be subject to different biases, the results produced are quite consistent. Mutated p53 in female family members of patients with Li-Fraumeni syndrome was one of the first identified genetic susceptibility markers for breast cancer. Application of segregation and linkage analyses to pedigrees with multiple affected family members successfully focused the search for BRCA1. Recent cloning and sequencing of BRCA1 will allow for its use in risk assessment, diagnostic evaluation and screening of high risk women. BRCA1 appears to be primarily responsible for early-onset breast cancer in high risk families. Rare alleles of H-ras could account for some of the late-onset cases in unselected populations since at least 85% of breast cancer appears to be sporadic, other genetic markers yet to be identified undoubtedly exist.


Subject(s)
Breast Neoplasms/epidemiology , Adult , Age Factors , Aged , Biomarkers , Breast/pathology , Breast Diseases/epidemiology , Breast Neoplasms/genetics , Disease Susceptibility , Epidemiologic Methods , Ethnicity/genetics , Female , Genes, Tumor Suppressor , Humans , Hyperplasia , Middle Aged , Obesity , Oncogenes , Pregnancy , Reproductive History , Risk , Risk Factors
15.
Environ Health Perspect ; 103 Suppl 8: 185-9, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8741781

ABSTRACT

A number of hormonal approaches for prevention of endometrial and breast cancers have been proposed. Because of the hormonal responsiveness of both tumors, much attention has focused on effects of exogenous hormone use. Although estrogens in hormone replacement therapy increase the risk of endometrial cancer, the disease is substantially reduced by long-term use of oral contraceptives. The issues with breast cancer are more complex, mainly because of a variety of unresolved effects. Long-term estrogen use is associated with some increase in breast cancer risk, and certain patterns of oral contraceptives appear to predispose to early-onset disease. With respect to estrogens, preventive approaches for both tumors would include use for as limited periods of time as possible. Addition of a progestin appears to lower estrogen-associated endometrial disease, but its effect on breast cancer risk remains less clear. Additional studies on effects of detailed usage parameters should provide useful insights into etiologic mechanisms. Other preventive approaches for endometrial cancer that may work through hormonal mechanisms include staying thin, being physically active, and maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by extended periods of breastfeeding, restriction of intake of alcoholic beverages, remaining thin later in life, and being physically active. Additional research is needed to clarify the biologic mechanisms of these associations. The bridging of epidemiology with the biologic sciences should clarify many unresolved issues and lead to better preventive approaches.


Subject(s)
Breast Neoplasms/prevention & control , Endometrial Neoplasms/prevention & control , Estrogens/administration & dosage , Progestins/administration & dosage , Breast Neoplasms/etiology , Endometrial Neoplasms/etiology , Estrogens/adverse effects , Female , Forecasting , Humans , Progestins/adverse effects , Research
16.
Lancet ; 346(8979): 883-7, 1995 Sep 30.
Article in English | MEDLINE | ID: mdl-7564675
17.
Breast Cancer Res Treat ; 35(1): 97-104, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7612910

ABSTRACT

Over the last several years, evidence has accumulated to support the idea that rare Ha-ras polymorphisms are associated with inherited susceptibility to certain human cancers. A recent epidemiologic study conducted at our institution found a significant association specifically with breast cancer, although the mechanism underlying this relationship remains unclear. We have proposed that rare Ha-ras alleles are markers of a genomic instability that predisposes to breast cancer. To address this hypothesis, we are investigating the relationship between the presence of rare alleles and another form of instability, gene amplification, and are developing new methodologies both to improve VNTR allele length detection and to characterize the internal repeat sequence variations of the various alleles. These studies should enable us to more clearly define the role of this region in cancer development by delineating VNTR structure and function and the mechanisms of rare allele generation. Ultimately, we hope to identify VNTR characteristics that will permit more accurate cancer risk assessment.


Subject(s)
Alleles , Breast Neoplasms/genetics , Genes, ras , Disease Susceptibility , Female , Humans , Minisatellite Repeats , Polymerase Chain Reaction , Polymorphism, Genetic , Risk Assessment
18.
Environ Health Perspect ; 103 Suppl 3: 3-8, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7635108

ABSTRACT

A symposium on Human Tissue Monitoring and Specimen Banking: Opportunities for Exposure Assessment, Risk Assessment, and Epidemiologic Research was held from 30 March to 1 April 1993 in Research Triangle Park, North Carolina. There were 117 registered participants from 18 states and 5 foreign countries. The first 2 days featured 21 invited speakers from the U.S. Environmental Protection Agency, the Centers for Disease Control and Prevention, the National Institute of Environmental Health Sciences, various other government agencies, and universities in the United States, Canada, Germany, and Norway. The speakers provided a state-of-the-art overview of human exposure assessment techniques (especially applications of biological markers) and their relevance to human tissue specimen banking. Issues relevant to large-scale specimen banking were discussed, including program design, sample design, data collection, tissue collection, and ethical ramifications. The final group of presentations concerned practical experiences of major specimen banking and human tissue monitoring programs in the United States and Europe. The symposium addressed the utility and research opportunities afforded by specimen banking programs for future research needs in the areas of human exposure assessment, risk assessment, and environmental epidemiology. The third day of the symposium consisted of a small workshop convened to discuss and develop recommendations to the U.S. Environmental Protection Agency regarding applications and utility of large-scale specimen banking, biological monitoring, and biological markers for risk assessment activities.


Subject(s)
Environmental Monitoring , Epidemiologic Methods , Hazardous Substances , Risk Assessment , Tissue Banks , Biomarkers , Epidemiological Monitoring , Europe , Humans , Research , Research Design , Tissue Banks/trends , United States
19.
Obstet Gynecol ; 85(3): 407-11, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7862381

ABSTRACT

OBJECTIVE: To determine the association between various forms of tobacco exposure and ovarian status, as measured by FSH concentrations, in women 38-49 years old. METHODS: Two hundred ninety women between 38-49 years old, who had not had hysterectomy or oophorectomy, completed a self-administered questionnaire that included information on tobacco exposure and had serum FSH levels measured on days 2-4 of the menstrual cycle. Linear regression was used to assess the relation between FSH and tobacco exposure. RESULTS: Controlling for age and other factors, FSH concentrations were 66% higher among current smokers (geometric mean FSH 14.0 mIU/mL) and 39% higher among nonsmokers with passive smoke exposure (11.7 mIU/mL), compared to nonsmoking women without passive smoke exposure (8.4 mIU/mL). The estimated increase in FSH for each year of age was greater for current smokers than for nonsmokers (16 versus 6%, respectively). Ex-smokers did not have higher FSH concentrations, and there was no association between prenatal exposure to tobacco smoke and FSH. CONCLUSION: Both active and passive smoking are associated with elevated FSH concentrations in women 38-49 years old. The effect, limited to women with current exposure, is consistent with a shorter duration of the menopausal transition period.


Subject(s)
Follicle Stimulating Hormone/blood , Smoking/blood , Tobacco Smoke Pollution , Adult , Case-Control Studies , Female , Humans , Linear Models , Middle Aged , Surveys and Questionnaires
20.
Fertil Steril ; 62(6): 1168-75, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7957979

ABSTRACT

OBJECTIVE: To test the hypothesis that high galactose consumption and low activity of galactose-1-phosphate uridyl transferase (transferase) is associated with early ovarian senescence among nongalactosemic women. DESIGN: Cross-sectional study. Data collection consisted of a self-administered questionnaire with sections on diet (food frequency data to measure galactose consumption), reproductive, and medical histories. One blood sample was collected to measure FSH and transferase activity; FSH was used as a measure of ovarian senescence. Among women who were having menstrual periods at least every 8 weeks, the blood sample was drawn in the early follicular phase (days 2 to 4) of a menstrual cycle. PARTICIPANTS: Two hundred ninety-five women volunteers ages 38 to 49 years who had not had a hysterectomy or oophorectomy were recruited through posters and advertisements. MAIN OUTCOME MEASURE: Serum FSH concentrations. RESULTS: Controlling for age, smoking, and body mass, transferase activity and FSH were unrelated. However, FSH levels were 29% higher (95% confidence intervals, 9% to 52%) among women who reported consuming > or = 6 g galactose/d. CONCLUSION: These data do not support the hypothesis that low transferase activity represents a genetic predisposition for early ovarian senescence, as measured by FSH levels in women ages 38 to 49 years. However, the hypothesized positive association between galactose consumption and FSH was supported.


Subject(s)
Aging/metabolism , Follicle Stimulating Hormone/blood , Galactose/administration & dosage , Galactose/metabolism , Adult , Cross-Sectional Studies , Diet , Estrogen Replacement Therapy , Female , Galactose/pharmacology , Humans , Menopause , Menstrual Cycle , Middle Aged , Osmolar Concentration , Transferases/blood
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