Hormonal risk factors for endometrial cancer: modification by cigarette smoking (United States).

OBJECTIVES: To evaluate whether smoking modifies the risk of endometrial cancer associated with body mass index (BMI), postmenopausal hormone use, and other hormonal factors. METHODS: Using multivariate adjusted models we examined interview data from a population-based case-control study of Wisconsin women (n = 740 cases, n = 2,372 controls). RESULTS: The relative risk for endometrial cancer associated with current smoking was 0.8 (95% CI: 0.6-1.0) compared to never smokers. No clear dose-response relationship was evident for pack-years smoked. When examined according to smoking status the risk associated with the highest quartile of BMI seemed to be greater among non-smokers (OR = 3.6, 95% CI: 2.4-5.3) than among current smokers (OR = 2.8, 95% CI: 1.4-5.6). Among postmenopausal women the risk associated with current use of postmenopausal hormones appeared to be greater among non-smokers (OR = 3.3, 95% CI: 2.3-4.9) than among current smokers (OR = 2.7. 95% CI: 1.3-5.5). Risk for long-term use (10 or more years) compared with never users was 8.3 (95% CI: 4.6-15.1) among never smokers and 2.5 (95% CI: 0.8-7.9) among current smokers. The risk associated with non-insulin-dependent diabetes was greater among non-smokers (OR = 2.5, 95% CI: 1.7-3.6) than current smokers (OR = 1.1, 95% CI: 0.4-3.1). There was no modifying effect of smoking on the risk associated with parity. CONCLUSION: These results suggest that smoking moderates the risk associated with endometrial cancer among women at greatest risk, specifically women who are obese or who use postmenopausal hormones.

The association of fatty acids with prostate cancer risk.

BACKGROUND: Animal studies indicate that omega-6 fatty acids promote and omega-3 fatty acids inhibit tumor development. This pilot study was designed to evaluate whether these fatty acids are associated with human prostate cancer. METHODS: Levels of erythrocyte membrane omega-3 and omega-6 fatty acids were determined for 67 incident prostate cancer cases and 156 population-based controls. RESULTS: Prostate cancer risk was increased in the highest compared to the lowest quartile of alpha-linolenic acid (OR = 2.6, 95% CI = 1.1-5.8, trend P = 0.01). Positive associations were also observed with higher levels of linoleic acid (OR = 2.1, 95% CI = 0.9-4.8) and total omega-6 fatty acids (OR = 2.3, 95% CI = 1.0-5.4). CONCLUSIONS: Results are consistent with other studies showing that linoleic and total omega-6 fatty acids increase risk of prostate cancer. Contrary to animal studies, alpha-linolenic acid was also positively associated with risk. Further research will be required to clarify the role of these fatty acids in human prostate cancer.

Effect of trimethoprim-sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis on bacterial illness, Pneumocystis carinii pneumonia, and death in persons with AIDS.

To measure the effect of trimethoprim-sulfamethoxazole (TMP-SMX) in preventing bacterial illness, Pneumocystis carinii pneumonia (PCP), and death in people with AIDS, we conducted a retrospective medical record review of 1078 persons who were observed for 3 years on average who attended nine outpatient facilities in Seattle, Washington between January 1990 and April 1996. We calculated relative risk estimates to measure the protective effect of TMP-SMX on the development of major bacterial illnesses, PCP, and death. Use of TMP-SMX decreased the risk of PCP (relative risk [RR] = 0.23; 95% confidence interval [CI], 0.14-0.36) and deaths not attributable to PCP (RR = 0.59; 95% CI, 0.47-0.73). Prevention of major bacterial illnesses of known etiology was of borderline significance (RR = 0.77; 95% CI, 0.57-1.05) and became statistically significant with the addition of patients with infections of unknown etiology (RR = 0.77; 95% CI 0.61-0.97). Use of TMP-SMX PCP prophylaxis significantly reduced the risks of death and of PCP and was associated with a trend toward reduced risk of major bacterial infections.

Temporal trends in rates of prostate cancer: declining incidence of advanced stage disease, 1974 to 1994.

PURPOSE: We examined the temporal trends in prostate cancer incidence and mortality rates in the Seattle-Puget Sound region. MATERIALS AND METHODS: Prostate cancer incidence and treatment data collected by the Cancer Surveillance System, part of the Surveillance, Epidemiology, and End Results program, were analyzed for temporal trends in disease and treatment. Analyses were restricted to white and African-American men 35 years or older residing in the 13-county area of northwestern Washington state and diagnosed between 1974 and 1994. Data for the treatment analyses were limited to the time period 1983 through 1992. RESULTS: Incidence of prostate cancer increased slowly from 1974 (169/100,000) to 1984 (230/100,000) and then rapidly to a peak in 1991 (486/100,000) before declining (293/100,000 in 1994). Mortality increased from 49/100,000 in 1974 to 67/100,000 in 1994. All stages of prostate cancer followed the same incidence trend peaking in 1991, except distant stage disease, which peaked in 1986 and subsequently declined by over 60% (p <0.001). Proportions of men undergoing radical prostatectomy increased from 1983 to 1992 with the biggest increase in men under 65 years old. CONCLUSIONS: The incidence rate of prostate cancer in the Seattle-Puget Sound region is higher than the rate in some other regions of the country. This is likely due to widespread, more intense prostate specific antigen screening of the population in this region compared to other areas of the country. The incidence rate of prostate cancer in the Seattle-Puget Sound region has peaked and is now declining.

Dehydroepiandrosterone sulfate and the risk of myocardial infarction in US male physicians: a prospective study.

High levels of dehydroepiandrosterone sulfate (DHEAS) have been associated with decreased risks of cardiovascular disease. The authors analyzed DHEAS in plasma collected at baseline among 169 participants in the Physicians' Health Study who subsequently had a myocardial infarction and 169 matched controls. The mean prediagnostic plasma DHEAS levels between cases (p = 0.33) (mean, 3.54 mumol/liter; standard deviation, 2.30) and controls (mean, 3.61 mumol/liter; standard deviation, 2.16) did not differ significantly. The relative risk was 1.04 (95 percent confidence interval 0.42-2.60) comparing extreme quintiles after adjustment for several coronary risk factors. In conclusion, these findings do not support the hypothesis that elevated plasma DHEAS is associated with a decreased risk of coronary disease in men, but a small to moderate association cannot be excluded.

A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians.

OBJECTIVE: To assess prospectively the risk of coronary heart disease associated with elevated plasma levels of homocyst(e)ine. DESIGN: Nested case-control study using prospectively collected blood samples. SETTING: Participants in the Physicians' Health Study. PARTICIPANTS: A total of 14,916 male physicians, aged 40 to 84 years, with no prior myocardial infarction (MI) or stroke provided plasma samples at baseline and were followed up for 5 years. Samples from 271 men who subsequently developed MI were analyzed for homocyst(e)ine levels together with paired controls, matched by age and smoking. MAIN OUTCOME MEASURE: Acute MI or death due to coronary disease. RESULTS: Levels of homocyst(e)ine were higher in cases than in controls (11.1 +/- 4.0 [SD] vs 10.5 +/- 2.8 nmol/mL; P = .03). The difference was attributable to an excess of high values among men who later had MIs. The relative risk for the highest 5% vs the bottom 90% of homocyst(e)ine levels was 3.1 (95% confidence interval, 1.4 to 6.9; P = .005). After additional adjustment for diabetes, hypertension, aspirin assignment, Quetelet's Index, and total/high-density lipoprotein cholesterol, this relative risk was 3.4 (95% confidence interval, 1.3 to 8.8) (P = .01). Thirteen controls and 31 cases (11%) had values above the 95th percentile of the controls. CONCLUSIONS: Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors. Because high levels can often be easily treated with vitamin supplements, homocyst(e)ine may be an independent, modifiable risk factor.

Baseline fibrinolytic state and the risk of future venous thrombosis. A prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor.

BACKGROUND: Although isolated abnormalities of plasminogen activation and inhibition have been reported among selected patients with venous thrombosis, it is unclear whether these deficiencies of fibrinolysis are important risk factors for thromboembolic disease. METHODS AND RESULTS: To evaluate whether baseline levels of endogenous tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) predict the future occurrence of venous thrombosis, levels of these proteins were measured in prospectively collected plasma samples from 55 participants in the Physicians' Health Study who later developed deep venous thrombosis or pulmonary embolism and from an equal number of age- and smoking-matched control subjects who remained free of vascular disease during a mean follow-up period of 60.2 months. Overall, there were no statistically significant differences between case patients and control subjects in baseline levels of PAI-1 (50.5 versus 59.5 ng/ml, p = 0.26), t-PA (13.4 versus 13.3 ng/ml, p = 0.94), or PAI-1:t-PA ratio (6.84 versus 6.58, p = 0.82). No evidence of a threshold effect or trend was seen when these data were analyzed by increasing quartiles of PAI-1 (p = 0.73), t-PA (p = 0.62), or PAI-1:t-PA ratio (p = 0.93). These results were unchanged after multivariate analysis that simultaneously controlled for other baseline cardiovascular risk factors. CONCLUSIONS: In contrast to previous uncontrolled case series and smaller retrospective studies, these prospective data provide strong evidence that baseline fibrinolytic state, as measured by t-PA and PAI-1, does not predict the occurrence of future venous thrombosis.