Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative Observational Study prospective cohort.

BACKGROUND: Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work). PATIENTS AND METHODS: The Women's Health Initiative Observational Study (WHI-OS) was a prospective cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999. Among 93 676 multiethnic participants aged 50-79, 76 304 women with complete smoking and covariate data comprised the analytic cohort. Lung cancer incidence was calculated by Cox proportional hazards models, stratified by smoking status. RESULTS: Over 10.5 mean follow-up years, 901 lung cancer cases were identified. Compared with never smokers (NS), lung cancer incidence was much higher in current [hazard ratio (HR) 13.44, 95% confidence interval (CI) 10.80-16.75] and former smokers (FS; HR 4.20, 95% CI 3.48-5.08) in a dose-dependent manner. Current and FS had significantly increased risk for all lung cancer subtypes, particularly small-cell and squamous cell carcinoma. Among NS, any passive smoking exposure did not significantly increase lung cancer risk (HR 0.88, 95% CI 0.52-1.49). However, risk tended to be increased in NS with adult home passive smoking exposure ≥30 years, compared with NS with no adult home exposure (HR 1.61, 95% CI 1.00-2.58). CONCLUSIONS: In this prospective cohort of postmenopausal women, active smoking significantly increased risk of all lung cancer subtypes; current smokers had significantly increased risk compared with FS. Among NS, prolonged passive adult home exposure tended to increase lung cancer risk. These data support continued need for smoking prevention and cessation interventions, passive smoking research, and further study of lung cancer risk factors in addition to smoking. CLINICALTRIALS.GOV: NCT00000611.

Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO).

BACKGROUND: The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated. METHODS: We performed a pooled analysis of six case-control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types. RESULTS: A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68-0.97) and HRT ever users (OR=0.77; 95% CI: 0.66-0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61-0.94, and OR=0.66; 95% CI: 0.49-0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37-0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66-0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19-0.71) in HRT users. No interaction with smoking status or BMI was observed. CONCLUSION: Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women.

Quality of life in endometrial cancer survivors by grade of disease.

BACKGROUND: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries, with overall incidence increasing, particularly high-grade disease. There is sparse information regarding quality of life (QOL) in EC survivors with a focus on grade of disease. METHODS: A total of 259 women with EC diagnosed between 2016 and 2020 were identified via the Metropolitan Detroit Cancer Surveillance System and consented to enroll in the Detroit Research on Cancer Survivors cohort study (if African American, n = 138) or completed the baseline interview (if non-Hispanic white, n = 121). Each respondent provided information about their health history, educational attainment, health behaviors, and demographics. The Functional Assessment of Cancer Therapy-General (FACT-G) and Endometrial-specific (FACT-En) were used to assess QOL. RESULTS: Women diagnosed with high-grade (n = 112) and low-grade (n = 147) EC participated in this study. EC survivors with high-grade disease reported significantly lower QOL compared to survivors with low-grade disease (85 vs. 91, respectively, p value = 0.025) as assessed by the FACT-G. This difference was driven by lower physical and functional subscales among women with high-grade disease compared to those with low-grade disease (p value = 0.016 and p = 0.028, respectively). Interestingly, EC-specific QOL measures, as assessed by the FACT-En, did not differ by grade. CONCLUSION: Grade of disease impacts QOL in EC survivors, as well as socioeconomic, psychological, and physical factors. Most of these factors are amenable to interventions and should be assessed in patients after an EC diagnosis.

Caregiving burden among informal caregivers of African American cancer survivors.

PURPOSE: Relatively little is known about caregivers of African American cancer survivors. Our goal was to identify the extent of burden among this group of caregivers. METHODS: Responses from 560 informal caregivers of African American participants of the Research on Cancer Survivors (ROCS) study in Detroit, MI, were analyzed including demographics, assistance provided including activities of daily living (ADLs) and instrumental activities of daily living (IADLs), time spent in caregiving, and caregiver burden (CGB). We assessed relationships between CGB and demographic variables, ADLs/IADLs, and level of care. Multivariable logistic regression determined which ADLs and IADLs were associated with high CGB. RESULTS: Over 75% of caregivers were female and 97% identified as African American. Mean age was 52.6 years. Fifty-six percent were employed outside the home, and 90% were related to the survivor. Caregivers averaged 35.7 h/week providing care, assisting with on average 2.8 ADLs and 5.0 IADLs. Despite the many hours and activities reported, no caregivers rated CGB as severe; only 4% rated it moderate to severe. ADLs associated with the top quartile of CGB were feeding and toileting; IADLs were finances, telephoning, housework, and medications. CONCLUSIONS: Caregivers for African American cancer survivors provide many hours of care, yet most describe their CGB as low. Although ADL assistance is often available through the healthcare system, assistance with IADLs presents an opportunity to lessen the burden for these caregivers and their care recipients. IMPLICATIONS FOR CANCER SURVIVORS: African American cancer survivors receive much care from informal family caregivers, who assist with multiple ADLs and IADLs. Formal IADL assistance programs, similar to those available for ADLs, would benefit both survivors and caregivers.

Effect of Cultural, Folk, and Religious Beliefs and Practices on Delays in Diagnosis of Ovarian Cancer in African American Women.

BACKGROUND: Certain cultural, folk, and religious beliefs that are more common among African Americans (AAs) have been associated with later-stage breast cancer. It is unknown if these beliefs are similarly associated with delays in diagnosis of ovarian cancer. METHODS: Data from a multicenter case-control study of ovarian cancer in AA women were used to examine associations between cultural/folk beliefs and religious practices and stage at diagnosis and symptom duration before diagnosis. Associations between cultural/folk beliefs or religious practices and stage at diagnosis were assessed with logistic regression analyses, and associations with symptom duration with linear regression analyses. RESULTS: Agreement with several of the cultural/folk belief statements was high (e.g., 40% agreed that "if a person prays about cancer, God will heal it without medical treatments"), and ∼90% of women expressed moderate to high levels of religiosity/spirituality. Higher levels of religiosity/spirituality were associated with a twofold increase in the odds of stage III-IV ovarian cancer, whereas agreement with the cultural/folk belief statements was not associated with stage. Symptom duration before diagnosis was not consistently associated with cultural/folk beliefs or religiosity/spirituality. CONCLUSIONS: Women who reported stronger religious beliefs or practices had increased odds of higher stage ovarian cancer. Inaccurate cultural/folk beliefs about cancer treament were not associated with stage; however, these beliefs were highly prevalent in our population and could impact patient treatment decisions. Our findings suggest opportunities for health education interventions, especially working with churches, and improved doctor-patient communication.

Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: a population-based study.

Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a population-based case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sex-matched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 Ile(462)Val and CYP1B1 Leu(432)Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 Msp1 or CYP1B1 Leu(432)Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the IIe/Val genotype at CYP1A1 Ile(462)Val locus were at decreased risk of having lung cancer compared to those with the lle/lle genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR=0.41 95% Cl 0.19-0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.

Secondary cancers after a lung carcinoid primary: a population-based analysis.

Carcinoid tumors of the lung were first described in 1937, yet little is known about their etiology. The aim of the present investigation was to determine if there was excess risk of secondary cancers in a population-based sample after a lung carcinoid tumor diagnosis which may provide insight to the etiology. Subjects were 1882 cases diagnosed with carcinoid tumors of the lung between 1988 and 2000 whose information was obtained from the Surveillance, Epidemiology and End Results (SEER) Program database. Standardized incidence ratios were calculated by dividing the observed number of second primary cancers by the expected number of cancers. Excess risk of breast cancer was seen following diagnosis of a carcinoid tumor (SIR=1.80 95% CI 1.22-2.55). When stratified by time after diagnosis, excess risk of breast cancers in women was seen in the first 5 years after carcinoid diagnosis (SIR=1.68 95% CI 1.08-2.50) but fewer than expected breast cancers were diagnosed greater than 5 years after carcinoid diagnosis (SIR=0.29 95% CI 0.09-0.68). Prostate cancers also occurred 2.8 times more often than expected (95% CI 1.66-4.43), with risk being elevated only in the first 5 years post-carcinoid diagnosis. Development of lung carcinoids may be the result of genetic predisposition or environmental exposures, particularly those that are hormonally related. The role of genetics and sex hormones in lung carcinoid development, as well as the identification of other risk factors, should be explored.

Risk of breast cancer to relatives of young breast cancer patients.

Breast cancer risk among sisters and mothers of a population-based series of 1,137 breast cancer patients diagnosed in Metropolitan Detroit before the age of 55 years was compared with risk to the same relatives of 1,001 age-matched, population-based controls. After adjusting for age of the relative, for age of the case or control, and for race, the odds ratio for breast cancer for women with affected sisters was 2.2; for women with affected daughters, 3.2; and for women with affected mothers and sisters, 9.9. Breast cancer in aunts had no independent influence on risk. Among white women, cumulative risk of breast cancer before the age of 50 years was approximately 1% for relatives of controls, 3% for sisters of older cases, but about 17% for women either with sisters diagnosed before the age of 40 years or with affected sisters and mothers. Sisters of the older patients had a 13% risk of breast cancer by 70 years of age, compared to 5% for sisters of controls. White women with affected mothers and sisters were at 50% risk by 65 years of age. This study identifies the criteria for women who could receive particular benefit from screening for breast cancer.

Relationship of leukemia risk to radiation dose following cancer of the uterine corpus.

BACKGROUND: Radiotherapy has been linked infrequently to secondary leukemia despite extensive exposure of the active bone marrow to ionizing radiation. Few studies include substantial numbers of elderly patients. PURPOSE: We evaluated women with cancer of the uterine corpus, the majority of whom were treated at older ages, to gain additional information on cancer risk following partial-body radiotherapy and to examine differences in risk between external-beam therapy and brachytherapy. METHODS: A cohort of 110,000 women with invasive cancer of the uterine corpus who survived at least 1 year following their initial cancer was assembled from nine population-based cancer registries. Cancer diagnoses occurred from 1935 through 1985, and most patients were diagnosed during the 1960s and 1970s. Radiation doses were computed to 17 sections of the active bone marrow for 218 women who developed leukemia and for 775 matched control subjects. RESULTS: Radiotherapy did not increase the risk of chronic lymphocytic leukemia (CLL) (relative risk [RR] = 0.90; 95% confidence interval [CI] = 0.4-1.9). However, for all leukemias except CLL, a significant risk was identified (RR = 1.92; 95% CI = 1.3-2.9). Overall, the pattern of risk in relation to dose was erratic and was most consistent with a constant increased risk across the entire dose range. The risk following continuous exposures from brachytherapy at comparatively low doses and low dose rates (RR = 1.80; 95% CI = 1.1-2.8; mean dose = 1.72 Gy) was similar to that after fractionated exposures at much higher doses and higher dose rates from external-beam treatment (RR = 2.29; 95% CI = 1.4-3.7; mean dose = 9.88 Gy), indicating a large difference in the estimated risk per unit dose. Risk did not vary by age at first exposure; increased risks were apparent for irradiated patients aged 65 years or older (RR = 1.77; 95% CI = 0.9-3.5). CONCLUSION: The leukemia risk associated with partial-body radiotherapy for uterine corpus cancer was small; about 14 excess leukemia cases were due to radiation per 10,000 women followed for 10 years. Women aged 65 years or older had a radiation risk comparable with that found in younger women. The relationship of leukemia risk to radiation dose was found to be complex due to the competing processes of cell killing, transformation, and repair. At very high doses delivered at high rates, destruction of cells likely dominates, and the risk per unit dose is low. In the low dose range, where dose was protracted and delivered at relatively low dose rates, the leukemia risk appears lower than that projected from risk estimates derived from the instantaneous whole-body exposures of atomic bomb survivors.

Familial risk of pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer-related mortality in the United STATES: Although smoking and age are known risk factors for pancreatic cancer, several case reports and case-control studies have suggested that there is also a familial risk. We evaluated whether a family history of pancreatic cancer increases the risk of pancreatic cancer in first-degree relatives and whether smoking and younger age at cancer diagnosis further increase this risk. METHODS: We conducted in-person interviews with 247 patients ("case probands") with pancreatic cancer and 420 population-based control probands to collect risk factor data and pancreatic cancer family history for 1816 first-degree relatives of the case probands and 3157 first-degree relatives of the control probands. We analyzed the data by unconditional logistic regression models, with adjustment for correlated data by use of generalized estimating equations. All statistical tests were two-sided. RESULTS: A positive family history of pancreatic cancer (i.e., being related to a case proband) or ever-smoking cigarettes approximately doubled the risk of pancreatic cancer (relative risk [RR] = 2.49; 95% confidence interval [CI] = 1.32 to 4.69; RR = 2.04; 95% CI = 1.09 to 3.83, respectively). The RR increased to 8.23 (95% CI = 2.18 to 31.07) for relatives who ever smoked and were related to a case proband who was diagnosed before age 60 years. CONCLUSION: Routine questioning of patients about a family history of pancreatic cancer, the age of onset of this cancer in their relatives, and the patient's smoking status may identify individuals at high risk of pancreatic cancer. Future research exploring the genetic and environmental interactions associated with the risk of pancreatic cancer is critically important.

Adenocarcinoma of the esophagus: role of obesity and diet.

BACKGROUND: In the United States, the incidence of adenocarcinoma of the esophagus, including the esophagogastric junction, has been increasing rapidly over the past two decades. Except for an association with Barrett's esophagus, little is known about the etiology of these cancers. PURPOSE: Our purpose was to investigate dietary and nutritional risk factors for adenocarcinoma of the esophagus. METHODS: A population-based, case-control interview study of 174 white men with adenocarcinoma of the esophagus and 750 control subjects living in three areas of the United States was conducted during 1986 through 1989. RESULTS: Risk was significantly elevated for subjects in the heaviest quartile compared with the lightest quartile of body mass index (odds ratio [OR] = 3.1; 95% confidence interval [CI] = 1.8-5.3). No significant associations were seen with total calories from food, number of meals eaten per day, level of fat intake, or consumption of coffee and tea. Risks were highest for those consuming the least amount of vegetables, with some evidence of a dose response for the subcategories of cruciferous vegetables (P for trend < .001) and vegetables consumed raw (P for trend = .10). A significantly elevated risk was also seen for those consuming the least amount of raw fruit (P for trend = .05). No clear associations were reported for intake of particular micronutrients overall or in supplements, but a significant protective effect was associated with increasing intake of dietary fiber (P for trend = .004). CONCLUSIONS: The findings of an increased risk with obesity and decreased risks with intake of raw fruits and vegetables and dietary fiber provide useful directions to pursue in further investigations of this malignancy. IMPLICATIONS: The finding with respect to obesity is particularly noteworthy, since it may explain at least a portion of the recent epidemic increases reported in the incidence of this tumor.

Are racial differences in squamous cell esophageal cancer explained by alcohol and tobacco use?

BACKGROUND: In the United States, incidence rates of squamous cell esophageal cancer are more than five times higher among black men than among white men. Reasons that might explain this large racial disparity are being sought. PURPOSE: We evaluated whether differential use of alcohol and tobacco can fully account for the excess of squamous cell esophageal cancer among U.S. blacks. METHODS: We conducted a population-based, case-control study with in-person interviews with 373 squamous cell esophageal cancer case patients (124 white males and 249 black males) and 1364 control subjects (750 white males and 614 black males) from three U.S. geographic areas. Histologically confirmed cases of squamous cell esophageal cancer newly diagnosed from August 1, 1986, through April 30, 1989, among white and black men aged 30-79 years were included. RESULTS: Alcohol use of more than one drink per day and/or current cigarette use of at least one pack per day accounted for 92.7% (95% confidence interval [CI] = 86.8%-98.5%) of the squamous cell esophageal cancers in blacks, versus 86.3% (95% CI = 75.5%-97.1%) in whites, and for 94% of the difference between the black and white annual incidence rates. The interaction between race and the continuous drinking/smoking variable in a logistic regression analysis was statistically significant (two-sided, P = .02). Exposure rates among controls at all levels of combined alcohol and tobacco use examined were slightly higher among blacks and accounted for a small portion of the racial differences in incidence rates. CONCLUSION: Although the vast majority of esophageal cancers in both blacks and whites in our data can be explained by use of alcohol and tobacco, it is not clear why heavy consumption of alcohol and/or tobacco is responsible for 14.9 per 100,000 per year more cases of squamous cell esophageal cancer among blacks than among whites. The differences in the odds ratios appear to account for more of the racial differences in incidence rates than do the prevalences of exposure to alcohol and tobacco alone. The reasons for this apparent racial difference in carcinogenic risk from the same level of alcohol and tobacco use are unknown, but they may include qualitative differences in alcohol consumption, differences in other environmental exposures that interact with alcohol and/or tobacco to modify risks, or differences in susceptibility to these factors.

Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews.

BACKGROUND: The relationship between diet and pancreatic cancer remains unclear. In this study, we assessed the role of diet and nutrition as risk factors for pancreatic cancer, using data obtained from direct interviews only, rather than data from less reliable interviews with next of kin. We evaluated whether dietary factors could explain the higher incidence of pancreatic cancer experienced by black Americans compared with white Americans. METHODS: We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. Reliable dietary histories were obtained for 436 patients and 2003 general-population control subjects aged 30-79 years. RESULTS: Obesity was associated with a statistically significant 50%-60% increased risk of pancreatic cancer that was consistent by sex and race. Although the magnitude of risk associated with obesity was identical in blacks and whites, a higher percentage of blacks were obese than were whites (women: 38% versus 16%; men: 27% versus 22%). A statistically significant positive trend in risk was observed with increasing caloric intake, with subjects in the highest quartile of caloric intake experiencing a 70% higher risk than those in the lowest quartile. A statistically significant interaction between body mass index (weight in kg/height in m2 for men and weight in kg/height in m1.5 for women) and total caloric intake was observed that was consistent by sex and race. Subjects in the highest quartile of both body mass index and caloric intake had a statistically significant 180% higher risk than those in the lowest quartile. CONCLUSIONS: Obesity is a risk factor for pancreatic cancer and appears to contribute to the higher risk of this disease among blacks than among whites in the United States, particularly among women. Furthermore, the interaction between body mass index and caloric intake suggests the importance of energy balance in pancreatic carcinogenesis.

Inhibition of spontaneous breast cancer formation in female C3H(Avy/a) mice by long-term treatment with dehydroepiandrosterone.

Long-term p.o. treatment with dehydroepiandrosterone, an adrenal steroid found in subnormal plasma concentrations in women predisposed to develop breast cancer, inhibits the formation of spontaneous mammary cancer in female C3H(Avy/a) mice.

Protective effect of dehydroepiandrosterone against aflatoxin B1-and 7,12-dimethylbenz(a)anthracene-induced cytotoxicity and transformation in cultured cells.

Dehydroepiandrosterone, an adrenal steroid that has been reported to be produced in subnormal amounts and found in lower plasma concentrations in women with benign and malignant breast tumors, protects cultured rat liver epithelial-like cells against aflatoxin B1-induced cytotoxicity and protects hamster embryonic fibroblasts against aflatoxin B1- and 7,12-dimethylbenz(a)anthracene-induced transformation. Related androgenic steroids show significantly less protective effect. Dehydroepiandrosterone also inhibits the rate of conversion of [3H]-7,12-dimethylbenz(a)anthracene to water-soluble metabolites by rat liver epithelial-like cells, suggesting that the steroid probably exerts its protective effect by inhibiting carcinogen activation.

Novel dehydroepiandrosterone analogues with enhanced biological activity and reduced side effects in mice and rats.

Treatment of laboratory mice and rats with the adrenal steroid, dehydroepiandrosterone (DHEA), produces antiobesity and broad spectrum tumor chemopreventive activity. Certain side effects are associated with DHEA administration which could limit its usefulness as a drug. DHEA can be metabolized into both testosterone and estrone and also increases liver weight and liver catalase activity. We have developed two synthetic steroids, 16 alpha-fluoro-5-androstan-17-one and 16 alpha-fluoro-5 alpha-androstan-17-one, which, unlike DHEA, do not stimulate uterine weight in sexually immature female rats or seminal vesicle weight in castrated male rats, nor stimulate liver weight and liver catalase activity in mice. 16 alpha-Fluoro-5-androsten-17-one is also about three times as potent as DHEA as an antiobesity agent and is more active when administered p.o. in inhibiting [3H]-7,12-dimethylbenz(a)-anthracene binding to skin DNA and tetradecanoylphorbol-13-acetate stimulation of epidermal [3H]thymidine incorporation in the mouse, two effects believed to be important in the tumor preventive action of DHEA. 16 alpha-Fluoro-5 alpha-androstan-17-one is as active as 16 alpha-fluoro-5-androsten-17-one in inhibiting [3H]-7,12-dimethylbenz(a)anthracene binding to skin DNA and tetradecanoylphorbol-13-acetate stimulation in epidermal [3H]thymidine incorporation but, on the contrary, is not more active than DHEA as an antiobesity drug. Compounds such as 16 alpha-fluoro-5-androsten-17-one and 16 alpha-fluoro-5 alpha-androstan-17-one, which lack specific side-effects of DHEA treatment and demonstrate greater potency, may have therapeutic application as drugs for humans.

Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin papillomas and carcinomas by dehydroepiandrosterone and 3-beta-methylandrost-5-en-17-one in mice.

Topical application of the adrenal steroid, dehydroepiandrosterone, or the synthetic steroid, 3-beta-methylandrost-5-en-17-one, which unlike dehydroepiandrosterone is not demonstrably uterotrophic, inhibits 7,12-dimethylbenz(a)anthracene-induced skin papillomas and carcinomas in the CD-1 mouse.

Antihyperglycemic effect of dehydroepiandrosterone analogue 16 alpha-fluoro-5-androsten-17-one in diabetic mice.

The adrenocortical steroid, dehydroepiandrosterone, has been shown previously to produce an antidiabetic effect in C57BL/KsJ db/db mice. Preliminary clinical data suggest that this steroid may enhance insulin sensitivity in humans. The therapeutic use of dehydroepiandrosterone may be limited by its androgenic action. In a previous study, high-dose dehydroepiandrosterone therapy to postmenopausal women produced marked elevations in plasma testosterone (9-fold) and dihydrotestosterone (20-fold) levels. We previously developed the synthetic steroid, 16 alpha-fluoro-5-androsten-17-one, which lacks the androgenic action of dehydroepiandrosterone yet has retained other biological activities of the native steroid. In this study, administration of 16 alpha-fluoro-5-androsten-17-one in the diet (0.2 and 0.3%) to male C57BL/KsJ db/db mice markedly reduced plasma glucose levels. In contrast, treatment with dehydroepiandrosterone was effective in reducing plasma glucose levels at the 0.2% dose but had no effect at the 0.3% dose, possibly as a result of the androgenic state induced at the higher dose. Dehydroepiandrosterone treatment also produced a 25-fold elevation in plasma testosterone levels and a significant increase in seminal vesicle weights, whereas treatment with 16 alpha-fluoro-5-androsten-17-one had no apparent effect on the weight of the seminal vesicle glands.

Clinical prediction of acute aortic dissection.

BACKGROUND: Clinical criteria for aortic dissection are poorly defined. Thus, 35% of aortic dissections remain unsuspected in vivo, and 99% of suspected cases can be refuted. OBJECTIVE: To identify independent predictors of acute aortic dissection and create a prediction model for facilitated estimation of the individual risk of dissection. METHODS: Two hundred fifty patients with acute chest pain, back pain, or both; absence of an established differential diagnosis of the pain syndrome; and clinical suspicion of acute aortic dissection were evaluated for the presence of 26 clinical variables in a prospective, observational study. Multivariate analysis was performed to create a prediction model of aortic dissection. RESULTS: Aortic pain with immediate onset, a tearing or ripping character, or both; mediastinal widening, aortic widening, or both on chest radiography; and pulse differentials, blood pressure differentials, or both (P<.001 for all) were identified as independent predictors of acute aortic dissection. Probability of dissection was low with absence of all 3 variables (7%), intermediate with isolated findings of aortic pain or mediastinal widening (31% and 39%, respectively), and high with isolated pulse or blood pressure differentials or any combination of the 3 variables (> or = 83%). Accordingly, 4% of all dissections were assigned to the low-probability group, 19% to the intermediate-probability group, and 77% to the high-probability group of aortic dissection. CONCLUSIONS: Assessment of 3 clinical variables permitted identification of 96% of the acute aortic dissections and stratification into high-, intermediate-, and low-probability groupings of disease. With better selection for prompt diagnostic imaging, this prediction model can be used as an aid to improve patient care in aortic dissection. Arch Intern Med. 2000;160:2977-2982

HLA and multiple myeloma among black and white men: evidence of a genetic association.

To evaluate the possibility that genetic factors contribute to the excess rates of multiple myeloma among blacks, serological typing of human leukocyte antigens (HLA) was conducted for black and white male patients and controls who participated in a large population-based case-control interview study. Forty-six black cases, 88 black controls, 85 white cases, and 122 white controls were typed for the Class I antigens (HLA-A, -B, -C) and for the Class II antigens (HLA-DR, HLA-DQ). Black cases had significantly higher gene frequencies than black controls for Bw65, Cw2, and DRw14, while white cases had higher gene frequencies than white controls for A3 and Cw2 and blanks at the DR and DQ loci. Further analysis of the association between Cw2 and multiple myeloma revealed relative risks of 5.7 (95% confidence interval = 1.5-26.6) and 2.6 (95% confidence interval = 1.0-7.2) for blacks and whites, respectively. The frequency of Cw2 in black and white controls was similar. These findings suggest that the Cw2 allele enhances the risk of myeloma in blacks and whites but do not explain the higher incidence of this cancer among blacks. The study also suggests that undefined DQ antigens may play an etiological role, supporting the need for further research into the immunogenetic determinants of myeloma.