Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter ≤ 2.5 (PM2.5) exposure were associated with morning serum cortisol levels. METHODS: In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1 ± 1.7 years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1 ± 0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12 months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA. RESULTS: Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1-7 months was associated with higher serum morning cortisol (p < 0.05) and longer term PM2.5 exposure (4-10 months) was associated with lower serum morning cortisol levels (p < 0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4-10 month exposure period associated with lower morning serum cortisol (p < 0.05). CONCLUSIONS: Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted.

Living near a freeway is associated with lower bone mineral density among Mexican Americans.

UNLABELLED: We hypothesized that chronic exposures to traffic combustion products may lower bone mineral density (BMD). We found that proximity to freeways was associated with reduced BMD. Our findings suggest that traffic-related pollution may contribute to the occurrence of osteopenia and osteoporosis. INTRODUCTION: Adults residing in rural areas have been linked with higher BMD. We aimed to determine if this difference is due in part to air pollution by examining the relationships between traffic metrics and ambient air pollution with total body and pelvic BMD. METHODS: Mexican American adults (n = 1,175; mean 34 years; 72 % female) who had participated in the BetaGene study of air pollution, obesity, and insulin resistance were included in this analysis. Total body and pelvic BMD were estimated using dual-energy X-ray absorptiometry. Traffic and ambient air pollutant exposures were estimated at residences using location and ambient monitoring data. Variance component models were used to analyze the associations between residential distance to the nearest freeway and ambient air pollutants with BMD. RESULTS: Residential proximity to a freeway was associated with lower total body BMD (p-trend = 0.01) and pelvic BMD (p-trend = 0.03) after adjustment for age, sex, weight, and height. The adjusted mean total body and pelvic BMD in participants living within 500 m of a freeway were 0.02 and 0.03 g/cm(2) lower than participants living greater than 1,500 m from a freeway. These associations did not differ significantly by age, sex, or obesity status. Results were similar after further adjustment for body fat and weekly physical activity minutes. Ambient air pollutants (NO2, O3, and PM2.5) were not significantly associated with BMD. CONCLUSIONS: Traffic-related exposures in overweight and obese Mexican Americans may adversely affect BMD. Our findings indicate that long-term exposures to traffic may contribute to the occurrence of osteoporosis and its consequences.

The effect of ambient air pollution on exhaled nitric oxide in the Children's Health Study.

We assessed the effect of daily variations in ambient air pollutants on exhaled nitric oxide fraction (F(eNO)) using data from a cohort of school children with large differences in air pollutant exposures from the Children's Health Study. Based on a cohort of 2,240 school children from 13 Southern Californian communities, cumulative lagged average regression models were fitted to determine the association between F(eNO) and ambient air pollution levels from central site monitors with lags of up to 30 days prior to F(eNO) testing. Daily 24-h cumulative lagged averages of particles with a 50% cut-off aerodynamic diameter of 2.5 µm (PM2.5; over 1-8 days) and particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10; over 1-7 days), as well as 10:00-18:00 h cumulative lagged average of O3 (over 1-23 days) were significantly associated with 17.42% (p<0.01), 9.25% (p<0.05) and 14.25% (p<0.01) higher F(eNO) levels over the interquartile range of 7.5 µg·m⁻³, 12.97 µg·m⁻³ and 15.42 ppb, respectively. The effects of PM2.5, PM10 and O3 were higher in the warm season. The particulate matter effects were robust to adjustments for effects of O3 and temperature and did not vary by asthma or allergy status. In summary, short-term increases in PM2.5, PM10 and O3 were associated with airway inflammation independent of asthma and allergy status, with PM10 effects significantly higher in the warm season.

Exhaled nitric oxide, susceptibility and new-onset asthma in the Children's Health Study.

A substantial body of evidence suggests an aetiological role of inflammation, and oxidative and nitrosative stress in asthma pathogenesis. Exhaled nitric oxide fraction (F(eNO)) may provide a noninvasive marker of oxidative and nitrosative stress, and aspects of airway inflammation. We examined whether children with elevated F(eNO) are at increased risk for new-onset asthma. We prospectively followed 2,206 asthma-free children (age 7-10 yrs) who participated in the Children's Health Study. We measured F(eNO) and followed these children for 3 yrs to ascertain incident asthma cases. Cox proportional hazard models were fitted to examine the association between F(eNO) and new-onset asthma. We found that F(eNO) was associated with increased risk of new-onset asthma. Children in the highest F(eNO) quartile had more than a two-fold increased risk of new-onset asthma compared to those with the lowest quartile (hazard ratio 2.1, 95% CI 1.3-3.5). This effect did not vary with the child's history of respiratory allergic symptoms. However, the effect of elevated F(eNO) on new-onset asthma was most apparent among those without a parental history of asthma. Our results indicate that children with elevated F(eNO) are at increased risk for new-onset asthma, especially if they have no parental history of asthma.

Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker of airway inflammation. In the nitric oxide (NO) synthesis pathway, nitric oxide synthases (encoded by NOS1, NOS2A, and NOS3) and arginases (encoded by ARG1 and ARG2) compete for L-arginine. Although FeNO levels are higher in children with asthma/allergy, influence of these conditions on the relationships between variations in these genes and FeNO remains unknown. The aims of the study were to evaluate the role of genetic variations in nitric oxide synthases and arginases on FeNO in children and to assess the influence of asthma and respiratory allergy on these genetic associations. METHODS: Among children (6-11 years) who participated in the southern California Children's Health Study, variations in these five genetic loci were characterized by tagSNPs. FeNO was measured in two consecutive years (N = 2298 and 2515 in Years 1 and 2, respectively). Repeated measures analysis of variance was used to evaluate the associations between these genetic variants and FeNO. RESULTS: Sequence variations in the NOS2A and ARG2 loci were globally associated with FeNO (P = 0.0002 and 0.01, respectively). The ARG2 association was tagged by intronic variant rs3742879 with stronger association with FeNO in asthmatic children (P-interaction = 0.01). The association of a NOS2A promoter haplotype with FeNO varied significantly by rs3742879 genotypes and by asthma. CONCLUSION: Variants in the NO synthesis pathway genes jointly contribute to differences in FeNO concentrations. Some of these genetic influences were stronger in children with asthma. Further studies are required to confirm our findings.

Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children.

BACKGROUND: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesised that glutathione-S-transferase (GST)P1, GSTM1, exercise and ozone exposure have interrelated effects on the pathogenesis of asthma. METHODS: Associations of the well characterised null variant of GSTM1 and four single nucleotide polymorphisms (SNPs) that characterised common variation in the GSTP1 locus with new onset asthma in a cohort of 1610 school children were examined. Children's exercise and ozone exposure were classified using participation in team sports and community annual average ozone levels, respectively. RESULTS: A two SNP model involving putatively functional variants (rs6591255, rs1695 (Ile105Va)) best captured the association between GSTP1 and asthma. The risk of asthma was lower for those with the Val allele of Ile105Val (hazard ratio (HR) 0.60, 95% CI 0.4 to 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95% CI 1.1 to 1.9). The risk of asthma increased with level of exercise among ile(105) homozygotes but not among those with at least one val(105) allele (interaction p value = 0.02). The risk was highest among ile(105) homozygotes who participated in >or=3 sports in the high ozone communities (HR 6.15, 95% CI 2.2 to 7.4). GSTM1 null was independently associated with an increased risk of asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth grade cohorts recruited in 1993 and 1996. CONCLUSION: Children who inherit a val(105) variant allele may be protected from the increased risk of asthma associated with exercise, especially in high ozone communities. GSTM1 null genotype was associated with an increased risk of asthma.

Ambient ozone modifies the effect of tumor necrosis factor G-308A on bronchitic symptoms among children with asthma.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has a recognized role in respiratory pathophysiology. One genetic variant (G-308A) in the promoter region affecting the expression of this cytokine may contribute to airway inflammatory diseases, but the studies on bronchitic symptoms were still inconclusive. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the TNF-308 polymorphism with bronchitic symptoms may vary by ambient ozone exposure. METHODS: We studied associations of TNF-308 genotype with bronchitic symptoms among asthmatic children in Children's Health Study. The association of TNF G-308A polymorphism with bronchitic symptoms was investigated and we also determined whether the associations vary with ambient ozone exposure. RESULTS: Asthmatic children with TNF-308 GG genotype had a significantly reduced risk of bronchitic symptoms with low-ozone exposure (adjusted OR: 0.53; 95% CI: 0.31-0.91). The risk was not reduced in children living in high-ozone communities (adjusted OR: 1.42; 95% CI: 0.75-2.70). This difference in genotypic effects between low- and high-ozone environments was statistically significant among asthmatics (P for interaction = 0.01), but insignificant among nonasthmatic children. CONCLUSION: Our findings suggest a role of gene-environmental interactions on the occurrence of bronchitic symptoms among children with asthma.

Associations of FcepsilonRIbeta E237G polymorphism with wheezing in Taiwanese schoolchildren.

BACKGROUND: The beta-chain of a high-affinity IgE receptor (FcepsilonRIbeta) has been proposed as a candidate gene for atopic diseases, but previous studies have come to inconsistent conclusions. Because some air pollutants would produce oxidative stress, increase serum IgE, and trigger T-helper type 2 (Th2)-type airway inflammation, the associations of FcepsilonRIbeta polymorphism with wheezing illness may vary by their exposures and variants of oxidant defence genes. The purpose of this study was to investigate the association of FcepsilonRIbeta E237G polymorphism with wheezing illness and to determine whether these associations vary with air pollution and glutathione S-transferase (GST) P1-105 and M1 genotypes. METHODS: In 2001, we conducted a case-control study comprised of 214 children with any history of wheezing and 185 non-wheezing controls, all of whom were selected from 2558 fourth- to ninth-grade schoolchildren in southern Taiwan. We examined differences in associations with ambient air pollution and by GST genotypes. RESULTS: Compared with the FcepsilonRIbeta EE genotype, children with the G allele had a significantly reduced risk of lifetime wheezing with low-ozone exposure [adjusted odds ratio (aOR)=0.25, 95% confidence interval (CI) 0.08-0.69]. The risk was not reduced in children living in high-ozone communities (aOR=0.98, 95% CI 0.57-1.67). This difference in genotypic effects between low- and high-pollution environments was statistically significant. The reduction of the protective effect from the G allele with higher air pollution was most marked in the GSTP1-105 Ile/Val or Val/Val and GSTM1 null groups. CONCLUSION: The FcepsilonRIbeta E237G allele may have a protective role in wheezing illness among Taiwanese schoolchildren, depending on airway oxidative stress levels.

Effects of air pollution exposure on glucose metabolism in Los Angeles minority children.

OBJECTIVES: Growing evidence indicates that ambient (AAP: NO2 , PM2.5 and O3 ) and traffic-related air pollutants (TRAP) contribute to metabolic disease risk in adults; however, few studies have examined these relationships in children. METHODS: Metabolic profiling was performed in 429 overweight and obese African-American and Latino youth living in urban Los Angeles, California. This cross-sectional study estimated individual residential air pollution exposure and used linear regression to examine relationships between air pollution and metabolic outcomes. RESULTS: AAP and TRAP exposure were associated with adverse effects on glucose metabolism independent of body fat percent. PM2.5 was associated with 25.0% higher fasting insulin (p < 0.001), 8.3% lower insulin sensitivity (p < 0.001), 14.7% higher acute insulin response to glucose (p = 0.001) and 1.7% higher fasting glucose (p < 0.001). Similar associations were observed for increased NO2 exposure. TRAP from non-freeway roads was associated with 12.1% higher insulin (p < 0.001), 6.9% lower insulin sensitivity (p = 0.02), 10.8% higher acute insulin response to glucose (p = 0.003) and 0.7% higher fasting glucose (p = 0.047). CONCLUSIONS: Elevated air pollution exposure was associated with a metabolic profile that is characteristic of increased risk for type 2 diabetes. These results indicate that increased prior year exposure to air pollution may adversely affect type 2 diabetes-related pathophysiology in overweight and obese minority children.

Prenatal traffic-related air pollution exposures, cord blood adipokines and infant weight.

OBJECTIVE: Studies suggest that prenatal exposure to traffic-related air pollution (TRAP) may contribute to childhood obesity. While exact mechanisms for this association are unknown, circulating adipokines are hypothesized to contribute to early-life weight gain. METHODS: The Maternal and Child Health Study birth cohort included 136 women from the Los Angeles County + University of Southern California Medical Center. This study estimated prenatal residential TRAP exposure and used linear regression analysis to examine associations between adipokines with TRAP exposure and infant weight change (birth to 6 months). RESULTS: A one standard deviation (1-SD: 2 ppb) increase in prenatal non-freeway nitrogen oxides was associated with 33% (P = 0.01) higher leptin and 9% higher high molecular weight adiponectin levels (P = 0.07) in cord blood. Leptin levels were 71% higher in mothers who lived <75 m than those living >300 m from major roadways (P = 0.03). A 1-SD (10 ng mL-1 ) increase in leptin was associated with a significant increase in infant weight change in female infants (0.62 kg, P = 0.02) but not male infants (0.11 kg, P = 0.48). CONCLUSIONS: Higher TRAP exposures were associated with higher cord blood levels of leptin and high molecular weight adiponectin. These adipokines were associated with increased infant weight change in female infants, which may have implications for future obesity risk.

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.

Biologic characteristics of interval and screen-detected breast cancers.

BACKGROUND: Interval breast cancer is defined as a cancer that is detected within 12 months after a negative mammogram. The failure of mammography to detect breast cancer depends on testing procedures, radiologist interpretation, patient characteristics, and tumor properties. Although errors by radiologists explain some interval cancers, another explanation is that the tumor is rapidly growing and was too small to be detected on the last mammogram. To determine whether markers of tumor growth rate are associated with risk of an interval cancer, we conducted a population-based study with the use of data collected statewide by the New Mexico Mammography Project. METHODS: Among women who received a mammographic examination from 1991 throughout 1993, we ascertained records of all patients with breast cancer diagnosed within 12 months of a negative screening mammographic examination (interval cancers) and corresponding tumor samples, when available. We selected an age- and ethnicity-matched comparison group of control patients with screen-detected breast cancers diagnosed during the same period. In tumor samples, p53, bcl-2, and Ki-67 were examined immunologically and the apoptotic index was assessed histologically. We used logistic regression to determine whether interval cancers were associated with selected demographic, radiologic, and biologic characteristics. RESULTS: It is more likely that mammography did not detect tumors with a high proportion of proliferating cells (>20%) than tumors with a low proportion of proliferating cells (<5%) (odds ratio [OR] = 4.09; 95% confidence interval [CI] = 1.14-14.65). The OR for mammographic failure was 2.96 (95% CI = 1.07-8.20) among cancers that expressed p53 compared with cancers that did not. Interval cancers also had fewer apoptotic cells. Approximately 75% of interval cancers appear to have tumors with 5% proliferating cells or more. Younger women had a higher proportion of rapidly proliferating and aggressive cancers. CONCLUSION: Rapidly growing and aggressive tumors account for a substantial proportion of mammographic failure to detect breast cancer, especially among younger women, who have a high proportion of aggressive cancers.

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

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.

Predicting lung cancer by detecting aberrant promoter methylation in sputum.

Despite the promise of using DNA markers for the early detection of cancer, none has proven universally applicable to the most common and lethal forms of human malignancy. Lung carcinoma, the leading cause of tumor-related death, is a key example of a cancer for which mortality could be greatly reduced through the development of sensitive molecular markers detectable at the earliest stages of disease. By increasing the sensitivity of a PCR approach to detect methylated DNA sequences, we now demonstrate that aberrant methylation of the p16 and/or O6-methyl-guanine-DNA methyltransferase promoters can be detected in DNA from sputum in 100% of patients with squamous cell lung carcinoma up to 3 years before clinical diagnosis. Moreover, the prevalence of these markers in sputum from cancer-free, high-risk subjects approximates lifetime risk for lung cancer. The use of aberrant gene methylation as a molecular marker system seems to offer a potentially powerful approach to population-based screening for the detection of lung cancer, and possibly the other common forms of human cancer.

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.

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.

Public health and clinical implications of high hemoglobin A1c levels and weight in younger adult Native American people with diabetes.

BACKGROUND: Type 2 diabetes mellitus is a major public health issue for Native American people. Because glycemic levels are predictive of diabetes outcome, understanding determinants of high hemoglobin A(1c) (HbA(1c)) levels may provide targets for prevention efforts. OBJECTIVES: To investigate determinants of high HbA(1c) levels in Native American people. METHODS: We conducted a population-based, cross-sectional study of 206 participants with diabetes from 8 Native American communities in New Mexico. We used linear regression to assess the relationship of HbA(1c) level with age, body mass index (BMI), treatment type, duration of diabetes, physical activity, and diet. RESULTS: Age, dietary pattern, and treatment type were determinants of HbA(1c) levels. Participants younger than 55 years had the highest adjusted HbA(1c) levels at 9.5% and those 65 years and older had the lowest levels at 7.8%. According to a participant's dietary intake, HbA(1c) levels were highest for those who consumed the most fat and sugar, and high consumption of fat and sugar affected HbA(1c) levels most among those younger than 55 years. Participants treated with insulin had the highest hemoglobin A(1c) levels. Physical activity was not associated with HbA(1c) level. CONCLUSIONS: We found an increasing severity of diabetes among younger people. To avoid increased morbidity and mortality in the future, young Native American adults with diabetes need vigorous therapy to maintain tight glucose control. Arch Intern Med. 2000;160:3471-3476.

Ethnic variation in prostate cancer survival in New Mexico.

Prostate cancer survival varies markedly by ethnicity. American Indians and blacks have the lowest 5-year relative survival among ethnic groups in the U.S. In New Mexico, relative survival for prostate cancer is lower for ethnic minority groups than for non-Hispanic whites. To examine factors underlying ethnic differences in prostate cancer survival in New Mexico, we analyzed Surveillance, Epidemiology, and End Results Program data collected by the New Mexico Tumor Registry from 1983 to 1992. Unadjusted relative risk (RR) of death after prostate cancer diagnosis was greater for Hispanics [RR = 1.1; 95% confidence interval (CI), 1.0, 1.2], American Indians (RR = 1.4; 95% CI, 1.2, 1.5), and blacks (RR = 1.5; 95% CI, 1.2, 1.7) than for non-Hispanic whites. After adjusting for age, stage, histological grade, year of diagnosis, and initial treatment, the risk for Hispanics (RR = 1.0; 95% CI, 0.9, 1.1), American Indians (RR = 1.0; 95% CI, 0.9, 1.1), and non-Hispanic whites was comparable. Although based on small numbers, adjusted risk ratios among blacks remained elevated (RR = 1.2; 95% CI, 0.9, 1.6), due in part to lower survival during the first 12 months after diagnosis (RR = 2.0; 95% CI, 1.2, 3.3) and poorer survival following radical prostatectomy (RR = 4.2; 95% CI, 1.3, 13). These findings suggest that poorer survival for Hispanics and American Indians may be explained by delayed detection and differences in treatment.

Rapid rise and subsequent decline in prostate cancer incidence rates for New Mexico, 1989-1993.

Beginning in the late 1980s, a large increase in incidence rates for prostate cancer occurred in association with increased prostate-specific antigen (PSA) screening. In New Mexico, the increased screening was associated with earlier detection of cancers and decreased prostate cancer mortality, suggesting that PSA screening may be effective. PSA screening has become a controversial topic of public debate, and anecdotal reports from physicians indicated that prostate cancer screening practice patterns were changing in New Mexico. To assess whether PSA-associated trends in prostate cancer incidence were continuing, we examined incidence rates from 1989 to 1993 among men in New Mexico. From 1989 to 1992, age-adjusted rates increased substantially for non-Hispanic whites (77%), Hispanics (50%), and American Indians (27%). Although rates increased for all stages combined, incidence rates decreased for distant-stage disease, especially for non-Hispanic whites, indicating a continuing trend toward earlier detection. In 1993, incidence rates unexpectedly decreased from 203 to 158/100,000 in non-Hispanic whites, largely as a result of changes in rates in men over age 65 years. Although incidence rates decreased, the trend toward earlier detection was maintained for non-Hispanic whites. In contrast, among Hispanic and American Indians, rates did not change substantially between 1992 and 1993. Because the epidemic in prostate cancer was associated with increased PSA screening, it is likely that the trends for non-Hispanic whites are also related to PSA screening. We suggest that the decrease in rates and the continued stage shift are consistent with repeated screening of men in the population at risk.