Childhood cancer and nuclear installations.
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Biomedical subjects
Publications and source records attributed to N C Lee.
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BACKGROUND: Nearly all studies have suggested that the use of oral contraceptives (OC) is not associated with the aggregate risk of breast cancer diagnosed in women aged 20-54 years. Because of age-specific differences in the breast cancer-parity relationship and because of age-specific differences in other breast cancer risk factors, the Centers for Disease Control reexamined data from the Cancer and Steroid Hormone Study (CASH) to assess whether OC use has different effects on the risk of breast cancer at different ages of diagnosis. METHODS: This population-based case-control study was designed to examine the relationship between the use of OC and the risk of breast, ovarian, and endometrial cancer. CASH was conducted in eight geographic areas in the United States during 1980-1982. All participants were interviewed at home with a pretested standardized questionnaire including a calendar of life events and a photograph book of all pills marketed in the United States. RESULTS: We found that the relationship between the risk of breast cancer and OC use appeared to vary by the age at diagnosis. Among women aged 20-34 years at diagnosis or interview, those who had ever used OC had a slightly increased risk of breast cancer (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0-2.1) compared with women of the same ages who had never used OC. Among these women, there were no trends of increasing or decreasing risk with any measure of OC use. Among women aged 35-44 years, there was no association between OC use and breast cancer. Among women aged 45-54 years, those who used OC had a slightly decreased risk of breast cancer (OR, 0.9; 95% CI, 0.8-1.0). Among these women, risk estimates decreased significantly with increasing time since first and last use. CONCLUSIONS: Although the slightly increased risk estimates for the youngest women were compatible with findings by other investigators, the decreased risk estimates for the oldest women have not been described in as many studies. Available data provide no reasons to change prescribing practices or the use of OC that are related to the breast cancer risk.
In case-control studies in which case and control enrollment periods are not identical, exposure status for time-dependent variables is often measured relative to a reference date. Using data from a case-control study of the relation between cervical cancer and oral contraceptive (OC) use in which control enrollment began 6 months after the end of case enrollment, we evaluated the effect on odds ratios from using five different reference dates to determine the controls' exposure status. The choice of reference date had little effect on the odds ratios in this study. Reference dates for time-dependent exposure variables should be considered carefully in studies when case and control enrollment periods are not identical.
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Short-term use (less than 1 year) or oral contraceptives has been associated with increased to slightly decreased risks of epithelial ovarian cancer in several studies. To determine what might account for a statistically significant 40% reduction in risk associated with as little as 3 to 6 months of use, a finding previously reported from the Cancer and Steroid Hormone Study, and to consider the implications for mechanisms of pathogenesis, the authors compared numerous characteristics of short-term users of oral contraceptives (41 cases, 412 controls) with those of never users (242 cases, 1,517 controls). The reduced risk among short-term users was consistently restricted to women who stopped using oral contraceptives for medical reasons, which were essentially side effects; there was little evidence of a protective effect among women who stopped for nonmedical reasons. Factors such as age, parity, family history of ovarian cancer, estrogen dose, history of sterilization, and latency (interval from first use) could not account for the finding. These analyses suggest that short-term use of oral contraceptives has little to no effect per se on reducing the risk of epithelial ovarian cancer and that side effects resulting in cessation of oral contraceptive use shortly after it was begun may be indicative of factors that are protective against the disease.
Breast and cervical cancer incidence and mortality rates were reviewed for the period 1973-1987. For breast cancer, mortality has been relatively stable, increasing from 26.9/100,000 women in 1973 to 27.1 in 1987. Alternatively, data from the National Cancer Institute's Surveillance, Epidemiology, End Results Program (SEER) showed a 36% increase in the incidence of this malignancy over the same period. In 1987, overall incidence of invasive breast cancer was 111.9/100,000 women. White women experienced lower overall mortality rates and higher overall incidence than black women; however, these differences varied by age. Examination of breast cancer incidence by stage of disease at diagnosis revealed that rates for distant and regional disease have remained relatively stable since 1973. In contrast, rates of localized and in situ cancers exhibited an increase in the 1980s that may correspond to increased use of mammography in this country. The rate of decline in cervical cancer incidence and mortality has slowed in recent years. In 1987, 3.0 cervical cancer deaths/100,000 women occurred. SEER incidence for invasive disease for that year was 8.2/100,000. Rates varied by race, age, state, and stage of disease. In general, black women experienced much higher incidence and mortality from invasive cervical cancer than white women. For both races, rates of in situ disease were highest among young women and decreased rapidly with age. Rates of in situ cervical cancer were consistently higher than rates of invasive cancer for the time period studied.
Specific histologic types of benign breast disease (BBD) may increase breast cancer risk. The authors analyzed data from a population-based, case-control study of women aged 20 to 54 with newly diagnosed breast cancer and control subjects randomly selected from the general population. A panel of pathologists classified the histologic findings of biopsy slides for 433 women with breast cancer and 261 control subjects, all of whom had a history of biopsy for BBD, as to the presence of epithelial hyperplasia, atypia, and other histologic features. When compared with women who had never had a breast biopsy, women with BBD without hyperplasia had an odds ratio of 1.5 (95% confidence limits [CL] 1.3 to 1.9), women with hyperplasia without atypia had an odds ratio of 1.8 (CL = 1.3, 2.4), and women with hyperplasia and atypia had an odds ratio of 2.6 (CL = 1.6, 4.1). Fibroadenoma was an independent risk factor for breast cancer (odds ratio = 1.7; CL = 1.1, 2.5). These findings suggest that women with BBD with epithelial hyperplasia either with or without atypia and women with fibroadenoma should be monitored carefully because of their elevated risk for breast cancer.
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The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined.
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Several hypotheses predict that tubal sterilization and hysterectomy may influence a woman's risk of developing ovarian cancer. To examine the relation between these surgeries and epithelial ovarian cancer, the authors analyzed data from the Cancer and Steroid Hormone Study, a case-control study of women aged 20-54 years. Eight population-based cancer registries in the United States identified women with newly diagnosed epithelial ovarian cancer during 1980-1982 (n = 494). A comparison sample of female residents of these eight areas (n = 4,238) was identified through random digit dialing. Women who had had tubal sterilization (relative risk (RR) = 0.69, 95% confidence interval (Cl) 0.50-0.95), a hysterectomy only (RR = 0.55, 95% Cl 0.38-0.81), or a hysterectomy with unilateral oophorectomy (RR = 0.60, 95% Cl 0.31-1.17) had lower risks of ovarian cancer than did women who had never had any sterilization surgery. However, the negative associations with tubal sterilization and hysterectomy only appeared to wane after two decades. These findings may be partly explained by the screening for occult ovarian pathology that often accompanies pelvic surgery: Women whose ovaries screen as "negative" may be temporarily at low risk of being diagnosed with ovarian cancer. However, because the decreased risks persisted for so long, it is conceivable that hormonal, mechanical, or circulatory sequelae of these sterilization procedures may act to lower ovarian cancer risk.
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The Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study of ovarian, breast, and endometrial cancer in women 20 to 54 years of age, permitted the diagnoses of contributing pathologists to be compared with those of a panel of three gynecologic pathologists. A diagnosis of ovarian cancer was made by contributing pathologists on 477 subjects. Agreement between the two groups of pathologists was 97% for primary epithelial ovarian cancer and 89% for primary nonepithelial ovarian malignancies. Agreement on diagnosis of major cellular subtypes of ovarian malignancy ranged between 73% for endometrioid cancer and 100% for clear cell carcinomas. We conclude that the diagnosis of pathologic features of primary ovarian cancer is highly predictable. Nonetheless, diagnosis by histologic type varies sufficiently that a review process should be considered for clinical or investigative decisions involving specific histologic diagnoses of ovarian cancer.