Factors associated with initial therapy for clinically localized prostate cancer: prostate cancer outcomes study.

BACKGROUND: Because of the lack of results from randomized clinical trials comparing the efficacy of aggressive therapies with that of more conservative therapies for clinically localized prostate cancer, men and their physicians may select treatments based on other criteria. We examined the association of sociodemographic and clinical characteristics with four management options: radical prostatectomy, radiation therapy, hormonal therapy, and watchful waiting. METHODS: We studied 3073 participants of the Prostate Cancer Outcomes Study diagnosed from October 1, 1994, through October 31, 1995, with clinically localized disease (T1 or T2). Participants completed a baseline survey, and diagnostic and treatment information was abstracted from medical records. Multiple logistic regression analysis identified factors associated with initial treatment. All statistical tests were two-sided. RESULTS: Patients with clinically localized disease received the following treatments: radical prostatectomy (47.6%), radiation therapy (23.4%), hormonal therapy (10.5%), or watchful waiting (18.5%). Men aged 75 years or older more often received conservative treatment (i.e., hormonal therapy alone or watchful waiting; 57.9% of men aged 75-79 years and 82.1% of men aged 80 years and older) than aggressive treatment (i.e., radical prostatectomy or radiation therapy) (for all age groups, P

Quality-of-life outcomes after primary androgen deprivation therapy: results from the Prostate Cancer Outcomes Study.

PURPOSE: To compare health-related quality-of-life outcomes after primary androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone-releasing hormone (LHRH) agonists for patients with prostate cancer. PATIENTS AND METHODS: Men (n = 431) newly diagnosed with all stages of prostate cancer from six geographic regions who participated in the Prostate Cancer Outcomes Study and who received primary AD therapy but no other treatments within 12 months of initial diagnosis were included in a study of health outcomes. Comparisons were statistically adjusted for patient sociodemographic and clinical characteristics, timing of therapy, and use of combined androgen blockade. RESULTS: More than half of the patients receiving primary AD therapy had been initially diagnosed with clinically localized prostate cancer. Among these patients, almost two thirds were at high risk of progression on the basis of prognostic factors. Sexual function outcomes were similar by treatment group both before and after implementation of AD therapy. LHRH patients reported more breast swelling than did orchiectomy patients (24.9% v 9.7%, P <.01). LHRH patients reported more physical discomfort and worry because of cancer or its treatment than did orchiectomy patients. LHRH patients assessed their overall health as fair or poor more frequently than did orchiectomy patients (35.4% v 28.1%, P =.01) and also were less likely to consider themselves free of prostate cancer after treatment. CONCLUSION: Most endocrine-related health outcomes are similar after surgical versus medical primary hormonal therapy. Stage at diagnosis had little effect on outcomes. These results provide representative information comparing surgical and medical AD therapy that may be used by physicians and patients to inform treatment decisions.

Health outcomes after external-beam radiation therapy for clinically localized prostate cancer: results from the Prostate Cancer Outcomes Study.

PURPOSE: Studies reporting effects of radiotherapy for prostate cancer on sexual, bowel, and urinary function have been conducted primarily in referral centers or academic institutions. Effects of external-beam radiotherapy for prostate cancer among a population-based cohort were assessed. PATIENTS AND METHODS: The study population included 497 white, Hispanic, and African-American men with localized prostate cancer from six US cancer registries who were diagnosed between October 1, 1994, and October 31, 1995, and treated initially with external-beam radiotherapy. They were interviewed at regular intervals, and medical records were reviewed. Distributions of responses for bowel-, urinary-, and sexual-related functions at 6, 12, and 24 months after diagnosis and adjusted mean composite change scores for each domain were analyzed. RESULTS: Declines of 28.9% in the sexual function score and 5.4% in the bowel function score occurred by 24 months, whereas at this time, the urinary function score was relatively unchanged. A total of 43% of those who were potent before diagnosis became impotent after 24 months. More than two thirds of the men were satisfied with their treatment and would make the same decision again. CONCLUSION: Sexual function was the most adversely affected quality-of-life domain, with problems continuing to increase between 12 and 24 months. Bowel function problems increased at 6 months, with partial resolution observed by 24 months. Despite the side effects, satisfaction with therapy was high. These results are representative of men in community practice settings and may be of assistance to men and to clinicians when making treatment decisions.

Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study.

BACKGROUND: African-Americans have twice the risk of non-Hispanic whites for presenting with advanced-stage prostate cancer. To investigate the reasons for this difference, we evaluated the association between race/ethnicity and advanced-stage prostate cancer, adjusting for demographic, socioeconomic, clinical, and pathologic factors. METHODS: A population-based cohort of 3173 men diagnosed with prostate cancer between October 1, 1994, and October 31, 1995, was analyzed. Medical record abstracts and self-administered survey questionnaires were used to obtain information regarding race/ethnicity, age, marital status, insurance status, educational level, household income, employment status, comorbidity, urinary function, prostate-specific antigen level, tumor grade, and clinical stage. The odds ratio (OR) for advanced-stage prostate cancer was estimated with weighted logistic regression analysis. All P: values were two-sided. RESULTS: Clinically advanced-stage prostate cancers were detected more frequently in African-Americans (12.3%) and Hispanics (10.5%) than in non-Hispanic whites (6.3%). Socioeconomic, clinical, and pathologic factors each accounted for about 15% of the increased relative risk. After adjusting for all covariates, the risk remained statistically significantly increased for African-Americans (OR = 2.26; 95% confidence interval [CI] = 1.43 to 3.58) but not for Hispanics (OR = 1.23; 95% CI = 0.73 to 2.08). CONCLUSION: Traditional socioeconomic, clinical, and pathologic factors accounted for the increased relative risk for presenting with advanced-stage prostate cancer in Hispanic but not in African-American men.

Health outcomes after prostatectomy or radiotherapy for prostate cancer: results from the Prostate Cancer Outcomes Study.

BACKGROUND: Radical prostatectomy and external beam radiotherapy are the two major therapeutic options for treating clinically localized prostate cancer. Because survival is often favorable regardless of therapy, treatment decisions may depend on other therapy-specific health outcomes. In this study, we compared the effects of two treatments on urinary, bowel, and sexual functions and on general health-related quality-of-life outcomes over a 2-year period following initial treatment. METHODS: A diverse cohort of patients aged 55-74 years who were newly diagnosed with clinically localized prostate cancer and received either radical prostatectomy (n = 1156) or external beam radiotherapy (n = 435) were included in this study. A propensity score was used to balance the two treatment groups because they differed in some baseline characteristics. This score was used in multivariable cross-sectional and longitudinal regression analyses comparing the treatment groups. All statistical tests were two-sided. RESULTS: Almost 2 years after treatment, men receiving radical prostatectomy were more likely than men receiving radiotherapy to be incontinent (9.6% versus 3.5%; P:<.001) and to have higher rates of impotence (79.6% versus 61.5%; P:<.001), although large, statistically significant declines in sexual function were observed in both treatment groups. In contrast, men receiving radiotherapy reported greater declines in bowel function than did men receiving radical prostatectomy. All of these differences remained after adjustments for propensity score. The treatment groups were similar in terms of general health-related quality of life. CONCLUSIONS: There are important differences in urinary, bowel, and sexual functions over 2 years after different treatments for clinically localized prostate cancer. In contrast to previous reports, these outcome differences reflect treatment delivered to a heterogeneous group of patients in diverse health care settings. These results provide comprehensive and representative information about long-term treatment complications to help guide and inform patients and clinicians about prostate cancer treatment decisions.

Validation study of retrospective recall of disease-targeted function: results from the prostate cancer outcomes study.

OBJECTIVES: This was an ancillary methodological study within the Prostate Cancer Outcomes Study (PCOS) to assess the validity of 6-month retrospective recall of prediagnostic disease-targeted function among men diagnosed with prostate cancer. METHODS: A convenience sample of 133 prostate cancer cases were administered a baseline questionnaire shortly after diagnosis that asked about prediagnostic urinary, sexual, and bowel function. They were surveyed again concerning the same items 6 months later and asked to recall their prediagnostic function. Reports of prediagnostic function obtained at baseline and 6 months are compared, as are measures of change derived from these reports. Percent agreement and weighted kappas are calculated to measure the extent of agreement. RESULTS: Over 70% of the men reported prediagnostic functioning at the highest level on 12 of 17 survey items. For each of these items, recall at 6 months was identical to the baseline survey response for > or =69% of the men. The values of the weighted kappas for changes computed with baseline reports (prospective) and changes computed with 6-month recall (retrospective) ranged from 0.396 to 0.919 for the 17 individual items. Intraclass correlations for the retrospective versus prospective changes in the multi-item function scores were 0.828 for urinary, 0.618 for bowel, and 0.692 for sexual function. CONCLUSIONS: At baseline, men recently diagnosed with prostate cancer report few disease-related problems before diagnosis, and a high percentage of men recall this accurately 6 months later. There is reasonably high agreement between baseline and 6-month estimates of prediagnostic function and between prospective and retrospective measures of change over 6 months.

Case-control assessment of the association between non-Hodgkin's lymphoma and occupational radiation with doses assessed using a job exposure matrix.

BACKGROUND: Epidemiologic data for an association between radiation exposure and non-Hodgkin's lymphoma (NHL) have been inconclusive though the strongest evidence has been provided by studies of patients treated with radiotherapy. METHODS: We evaluated the association between occupational radiation exposure and non-Hodgkin's lymphoma in men using a population-based case-control study with 1,056 case and 1,860 control subjects sampled from eight geographic areas in the United States. Because dosimetry data were not available, doses were estimated for individuals who reported occupational radiation exposure using a radiation job exposure matrix developed for this purpose. Conditional logistic regression was used to model the association between reported occupational radiation exposure and NHL incidence. RESULTS: We found that most men (> 90%) did not report exposure to occupational sources of radiation. Among those who reported exposure, estimated cumulative doses were low, with an estimated mean of less than 0.02 Gray and a maximum of 0.12 Gray. The risk for NHL was not associated with ever having reported an occupational radiation exposure (OR = 0.90, 95% CI = 0.74-1.10) nor was there evidence of a dose-response relationship between risk and either the estimated cumulative doses or duration of exposure. CONCLUSIONS: The findings in this study are consistent with results from most current research on occupational radiation and NHL risk that have found no increased risk of NHL at low levels of occupational radiation exposure. While it should be noted that exposure misclassification likely biased our results toward the null, this large population-based case-control study adds to existing evidence which suggests that there is little to no increased risk for NHL associated with exposure to low levels of radiation such as that commonly found in many occupational settings.

Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study.

CONTEXT: Patients with prostate cancer and their physicians need knowledge of treatment options and their potential complications, but limited data on complications are available in unselected population-based cohorts of patients. OBJECTIVE: To measure changes in urinary and sexual function in men who have undergone radical prostatectomy for clinically localized prostate cancer. DESIGN: The Prostate Cancer Outcomes Study, a population-based longitudinal cohort study with up to 24 months of follow-up. SETTING: Population-based cancer registries in 6 geographic regions of the United States. PARTICIPANTS: A total of 1291 black, white, and Hispanic men aged 39 to 79 years who were diagnosed as having primary prostate cancer between October 1, 1994, and October 31, 1995, and who underwent radical prostatectomy within 6 months of diagnosis for clinically localized disease. MAIN OUTCOME MEASURES: Distribution of and change in urinary and sexual function measures reported by patients at baseline and 6, 12, and 24 months after diagnosis. RESULTS: At 18 or more months following radical prostatectomy, 8.4% of men were incontinent and 59.9% were impotent. Among men who were potent before surgery, the proportion of men reporting impotence at 18 or more months after surgery varied according to whether the procedure was nerve sparing (65.6% of non-nerve-sparing, 58.6% of unilateral, and 56.0% of bilateral nerve-sparing). At 18 or more months after surgery, 41.9% reported that their sexual performance was a moderate-to-large problem. Both sexual and urinary function varied by age (39.0% of men aged <60 years vs 15.3 %-21.7% of older men were potent at > or =18 months [P<.001]; 13.8% of men aged 75-79 years vs 0.7%-3.6% of younger men experienced the highest level of incontinence at > or =18 months [P = .03]), and sexual function also varied by race (38.4% of black men reported firm erections at > or =18 months vs 25.9% of Hispanic and 21.3% of white men; P = .001). CONCLUSIONS: Our study suggests that radical prostatectomy is associated with significant erectile dysfunction and some decline in urinary function. These results may be particularly helpful to community-based physicians and their patients with prostate cancer who face difficult treatment decisions.

Predicting extracapsular extension of prostate cancer in men treated with radical prostatectomy: results from the population based prostate cancer outcomes study.

PURPOSE: We investigated whether clinical information routinely available in community practice could predict extracapsular extension of clinically localized prostate cancer in men undergoing radical prostatectomy. MATERIALS AND METHODS: We examined prostate cancer outcomes in a population based sample of 3,826 patients with primary prostate cancer in 6 regions of the United States covered by the Surveillance, Epidemiology, and End Results program. Stratified and weighted logistic regression was used to identify predictors of and probabilities for extracapsular extension of clinically localized tumors treated with radical prostatectomy. RESULTS: Nearly 47% of men undergoing radical prostatectomy had extraprostatic extension. The strongest predictors were elevated prostate specific antigen (PSA) greater than 20 versus less than 4 ng./ml. (odds ratio 5.88, 95% confidence interval 2.90 to 11.15), Gleason score greater than 8 versus less than 6 (1.73, 1.04 to 2.87) and age greater than 70 versus less than 50 years (1.91, 0.98 to 3.70). Ethnicity and region were not associated with increased risk of extraprostatic extension. A nomogram developed from our model predicts extracapsular extension ranging from 24% in men younger than 50 years with PSA less than 4 ng./ml. and a Gleason score of less than 7 to 85% in those 70 years old or older with PSA greater than 20 ng./ml. and a Gleason score of 8 or more. If prostatectomy were limited to patients with less than 60% probability of extraprostatic extension based on the nomogram, 95% of those with organ confined cancers would undergo definitive surgery and 18% of those with extracapsular extension would be spared the morbidity of surgery. CONCLUSIONS: In a population based analysis of prostate cancer practice patterns PSA, Gleason score and age are clinically useful predictors of extracapsular extension. Although extracapsular extension may be an imperfect predictor of cancer outcomes, our nomogram provides more realistic probabilities for extracapsular extension than those based on institutional series.

Racial differences in endometrial cancer survival: the black/white cancer survival study.

OBJECTIVE: To identify factors that explain a lower survival rate among black women with endometrial cancer when compared to white women. METHODS: Data are from the National Cancer Institute's Black/White Cancer Survival Study, a population-based study of racial differences in cancer survival. Subjects included 329 white and 130 black women, ages 20-79 years, residing in the metropolitan areas of Atlanta, New Orleans, or San Francisco-Oakland, diagnosed with endometrial cancer from 1985 to 1987. Known prognostic factors were assessed as potential explanatory variables for the black-white survival difference using proportional hazards regression. Information was derived from interviews, abstracts of hospital and physicians' records, and a centralized review of biopsy and surgical specimens. RESULTS: Adjusting for age and geographic location, risk of death among black women was 4.0 times (95% confidence interval [CI] 2.8, 5.6) that of white women. Approximately 40% of this difference could be attributed to a more advanced stage at diagnosis among black women, and 23% to tumor characteristics and treatment. Further adjustment for all remaining factors reduced the hazard ratio to 1.6 (95% CI 1.0, 2.6). CONCLUSION: Eighty percent of the excess mortality among black women is explained by racial differences in stage at diagnosis, tumor characteristics, treatment, sociodemographic characteristics, hormonal and reproductive factors, and factors related to comorbidities and health behavior. Difference in stage at diagnosis is prominent in explaining the disparity in endometrial cancer survival rates in black and white women. Potential differences in treatment within stage merit further exploration.

Cine-MRI-aided endomyocardectomy in idiopathic hypereosinophilic syndrome.

The idiopathic hypereosinophilic syndrome is a leukoproliferative disorder marked by a predilection to damage specific organs, including the heart. This report describes a patient with extensive endocardial fibrosis accompanying this syndrome. Right ventricular endomyocardectomy with preservation of the tricuspid valve was performed. The procedure was aided by cine-magnetic resonance imaging for preoperative assessment and follow-up of surgical results.

Linking health services research to education at an academic health center.

Academic health centers (AHCs) face numerous challenges as they prepare students, housestaff, and faculty for the rapidly changing health care environment. An already overburdened curriculum makes it difficult to provide medical students with skills in outcomes assessment, health economics, clinical decision making, epidemiology, and basic statistics. Practicing physicians may find it difficult to expend the time and resources needed for degree programs in public health or the evaluative clinical sciences. AHCs may need to tap into existing resources in the health evaluation sciences, as Emory University (Atlanta, Georgia) has done by establishing the Emory University Center for Clinical Evaluation Sciences. Although the Center's primary missions are to be an analytical resource for Emory's health care delivery system and to promote health services research across the university, the authors illustrate its potential as a resource for training medical students, housestaff, and faculty in the evaluative clinical sciences.

Differences between black and white patients with cancer of the uterine corpus in interval from symptom recognition to initial medical consultation (United States).

To determine whether Black women with symptoms of uterine corpus cancer had longer times from symptom recognition to initial medical consultation than did White women in the United States, 331 newly diagnosed patients living in Atlanta (GA), New Orleans (LA), and San Francisco/Oakland (CA) during 1985-87 were interviewed to collect information on symptoms, dates of recognition and consultation, and other factors that might affect the interval. Data were analyzed to estimate medical consultation rates and rate ratios following symptom recognition. Median recalled times between symptom recognition and consultation were 16 days for Black women and 14 days for White women. Although poverty, having no usual source of healthcare, and other factors were associated with lower consultation rates, the adjusted rate among Black women was only somewhat lower (0.87) than among White women, and the 95 percent confidence interval (CI = 0.58-1.31) was consistent with no true difference between the races. In addition, the median time to consultation for women with stage IV cancer was only 15 days longer than the time (14 days) for the women with stage I cancer. These results suggest that time from symptom recognition to initial medical consultation does not contribute importantly to the more advanced stage cancer of the uterine corpus commonly found among Black women.

High dose cyclophosphamide, fractionated total body irradiation with involved field irradiation and autologous bone marrow transplantation in malignant lymphoma.

The objective of this clinical trial was to determine if radiation to areas of recurrence or bulky disease prior to total body irradiation (TBI) and chemotherapy followed by autologous bone marrow transplantation (ABMT) altered the site of relapse and/or prolonged survival. Forty-eight patients with recurrent or refractory malignant lymphoma were treated with high-dose cyclophosphamide and fractionated TBI followed by ABMT. Thirty-four patients were eligible to receive involved field radiation therapy (IF-RT) to sites of recurrence or bulky disease. The overall response rate in 46 evaluable patients was 89% with 33 complete remissions (CR) and 8 partial remissions (PR). In a multivariant analysis increasing LDH, decreased serum albumin, older age, and lack of sensitivity to prior chemotherapy were associated with poorer survival. There were 10 deaths due to treatment related complications, 8 died of pulmonary complications of whom 6 were in CR. Of 11 who had received IF-RT and subsequently relapsed, 4 recurred in or adjacent to the involved field. We conclude that intensive chemo-radiotherapy proved to be an effective salvage therapy for patients with recurrent malignant lymphoma, resulting in a projected actuarial 33% DFS at 5 years, but was associated with a high transplant-related mortality.

Endometrial cancer: stage at diagnosis and associated factors in black and white patients.

OBJECTIVE: This study examined the relationship of clinicopathologic, health status, medical system, and socioeconomic factors to differences in stage at diagnosis of endometrial cancer in black and white patients. STUDY DESIGN: A population-based study of 130 black and 329 white patients with invasive endometrial cancer was conducted as part of the National Cancer Institute's Black/White Cancer Survival Study. Logistic regression was used to determine the relative importance of factors thought to be related to stage at diagnosis after age and geographic location were adjusted for. RESULTS: High-grade (poorly differentiated) lesions increased the risk for stage III or IV disease (odds ratio 8.3, 95% confidence interval 3.4 to 20.3), as did serous histologic subtype (odds ratio 3.5, 95% confidence interval 1.4 to 8.8) and no usual source of care (odds ratio 5.5, 95% confidence interval 1.4 to 20.9). In the final statistical model these three factors also accounted for the majority of the excess risk of advanced stage for blacks. CONCLUSIONS: Black-white racial disparities in stage at diagnosis appear to be related to higher-grade lesions and more aggressive histologic subtypes occurring more frequently in black patients with endometrial cancer.

Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study.

OBJECTIVE: To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts. DESIGN AND PARTICIPANTS: Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens. MAIN OUTCOME MEASURE: Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors. RESULTS: After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio = 1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer-specific mortality. CONCLUSIONS: Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women.

Histological characteristics of breast carcinoma in blacks and whites.

Tumor characteristics of 963 newly diagnosed invasive breast cancer cases from the population-based Black/White Cancer Survival Study were evaluated. Representative slides of the tumors were requested from all participating hospitals of three metropolitan areas and reviewed by one expert pathologist, blinded in regard to the age and race of patients. Nine tumor characteristics were evaluated for black and white patients. After adjusting for age, stage, and metropolitan area, blacks were significantly more likely to have high grade nuclear atypia [odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.27-3.04]; high mitotic activity (OR = 2.05, 95% CI = 1.34-3.14), grade 3 tumors (OR = 1.58, 95% CI = 1.02-2.45), and more necrosis (OR = 1.51, 95% CI = 1.16-1.98); and less likely to have well defined tubular formation (OR = 0.57, 95% CI = 0.42-0.77), marked fibrosis (OR = 0.65, 95% CI = 0.45-0.94), and positive estrogen receptor status (OR = 0.78, 95% CI = 0.58-1.05). These black/white differences remained after controlling for socioeconomic status (SES), body mass index, use of alcohol and tobacco, reproductive experience, and health care access and utilization. No significant racial differences were found for blood vessel invasion and lymphatic invasion. Although white women of high SES had more favorable tumors than those of low SES, the same pattern was not observed for blacks. High SES black women had statistically nonsignificant elevated ORs of a high mitotic index and tumor grade. These racial differences in tumor biology may have etiological and clinical implications.

Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level.

Glutathione may function as an anticarcinogen by acting as an antioxidant or by binding with cellular mutagens. Orally administered glutathione increases plasma glutathione levels, and plasma glutathione is also synthesized in the liver. To investigate the associations between glutathione intake and plasma glutathione level, we compared dietary intake estimates from food frequency questionnaire data and measured concentrations of plasma total glutathione and other serum antioxidants in 69 white men and women. Daily glutathione intake ranged from 13.0 to 109.9 mg (mean 34.8 mg). Fruits and vegetables were found to contribute over 50% of usual dietary glutathione intake, whereas meats contributed less than 25%. Small negative correlations were observed between dietary and plasma glutathione and, although they were usually not statistically significant, they were generally consistent by different time periods of dietary intake assessment. Adjustment for sex, age, caloric intake, and dietary intake of the sulfur-containing amino acids methionine and cystine did not alter the observed associations. The correlations appeared to be modified, however, by serum vitamin C concentration, with little or no association between dietary and plasma glutathione among those with lower levels of serum vitamin C and stronger negative correlations among those with higher serum vitamin C levels. These findings indicate that factors regulating plasma glutathione concentration are complex and not simply related to dietary glutathione intake or supply of precursor amino acids.

Plasma total glutathione in humans and its association with demographic and health-related factors.

The tripeptide glutathione is proposed to be protective against a number of chronic diseases including cardiovascular disease and cancer. However, there have been few studies of plasma glutathione levels in humans and in those studies the numbers of participants have been very small. In an exploratory analysis the determinants of plasma total glutathione (GSHt) were investigated in a group of 100 volunteers aged 18-61 years in Atlanta, Georgia, USA during June and July 1989. Data on demographic and health-related factors were collected by interview and plasma GSHt was measured using a recently modified laboratory method. The mean concentration of plasma GSHt for all 100 participants was 761 micrograms/l, with a standard deviation of 451 micrograms/l, a range of 86-2889 micrograms/l and a median of 649 micrograms/l. Men had significantly higher levels of plasma GSHt than women (924 v. 692 micrograms/l; P = 0.006). Seventh-day Adventists participating in the present study had higher plasma GSHt levels than other subgroups defined by race and/or religion. Among Seventh-day Adventists consumption of a vegetarian diet was associated with increased plasma GSHt concentration (P = 0.002). Plasma GSHt levels also appeared to vary by race, but relationships with race could not be clearly disassociated from relationships with religion. Among white participants plasma GSHt concentration decreased with age in women but increased with age in men (P = 0.05). Few other factors were associated with plasma GSHt concentration, although use of oral contraceptives (P = 0.10) was somewhat associated with decreased plasma GSHt levels. These findings suggest that plasma GSHt levels may vary with several demographic and health-related attributes and support the need for further research on this potentially important disease-preventive compound.