Biomedical subjects

Frank D Gilliland

Publications and source records attributed to Frank D Gilliland.

At least 19 recordsLinked to original sources

PubMed2006

Associations between the CYP17, CYPIB1, COMT and SHBG polymorphisms and serum sex hormones in post-menopausal breast cancer survivors.

Several polymorphisms have been identified in genes that code for enzymes involved with estrogen biosynthesis and metabolism. Little is known about the functional relevance of these polymorphisms on sex hormones in vivo. We examined the association between CYP17, CYP1B1, COMT or SHBG genotypes and serum concentrations of estrone, estradiol, free estradiol, sex hormone-binding globulin (SHBG), testosterone, free testosterone and dehyroepiandrosterone in 366 post-menopausal breast cancer survivors in New Mexico, California and Washington. Hormone levels were determined by high performance liquid chromatography and radioimmunoassay in blood drawn approximately 2 years post-diagnosis. We used generalized linear regression to calculate mean hormone levels by genotype, adjusting for age, race/ethnicity, stage, study site, tamoxifen use, number of remaining ovaries, hormone therapy use, marital status and BMI. No associations were observed between any of the genotypes and sex hormones when analyzing the main effects. In subgroup analyses, androgen levels of Hispanic women with the variant (A2) CYP17 genotype were 46-87% higher than those of women with the wild-type; androgen levels were 13-20% lower in non-Hispanic whites with the variant genotype; no difference by genotype was observed for African-American women. Current tamoxifen users with the variant asn(327) SHBG genotype had 81% higher serum SHBG and 39% lower free testosterone concentrations than women with the wild-type genotype. Non-tamoxifen users with the variant SHBG allele had elevated free estradiol levels. These results provide little evidence that the CYP17, CYP1B1, and COMT polymorphisms are associated with different sex hormone levels in post-menopausal breast cancer survivors.

Adolescent↗

PubMed2006

Glutathione s-transferases M1 and P1 prevent aggravation of allergic responses by secondhand smoke.

RATIONALE: Secondhand tobacco smoke (SHS) and traffic-related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione S-transferases (GSTs) metabolize reactive oxygen species and detoxify electrophilic xenobiotics present in SHS and DEPs. OBJECTIVES: We tested the hypotheses that functional GSTM1-null genotype and GSTP1 codon 105 variants (Ile105 and Val105) are determinants of allergic responses to SHS, and that responses to SHS and DEPs are correlated. METHODS AND MEASUREMENTS: In a randomized, placebo-controlled crossover trial, 19 ragweed allergen-sensitive subjects who had previously participated in a DEP trial were challenged intranasally with allergen after having been exposed to either clean air or SHS at separate visits. Nasal allergen-specific IgE, histamine, IL-4, and IFN-gamma levels were measured before and after allergen challenge. MAIN RESULTS: Individuals with GSTM1-null or GSTP1 Ile105 genotypes showed larger nasal responses to allergens with SHS compared with clean air. GSTM1-null subjects had a larger increase in IgE than GSTM1-present subjects (median, 173.3 vs. 46.7 U/ml; p = 0.03), and the Ile105 GSTP1 genotype subjects had increased histamine (median, 10.2 vs. 4.6 nM; p = 0.01) after SHS plus allergen challenge. Responses to SHS and DEPs were correlated. Enhancement of IgE and histamine was greatest in the subjects with both the GSTM1-null and GSTP1 Ile/Ile genotypes. CONCLUSIONS: GSTM1 and GSTP1 are important cytoprotective factors that reduce SHS and DEP exacerbation of allergic responses.

Adult↗

PubMed2006

Regular smoking and asthma incidence in adolescents.

RATIONALE: Although involuntary exposure to maternal smoking during the in utero period and to secondhand smoke are associated with occurrence of childhood asthma, few studies have investigated the role of active cigarette smoking on asthma onset during adolescence. OBJECTIVES: To determine whether regular smoking is associated with the new onset of asthma during adolescence. METHODS: We conducted a prospective cohort study among 2,609 children with no lifetime history of asthma or wheezing who were recruited from fourth- and seventh-grade classrooms and followed annually in schools in 12 southern California communities. Regular smoking was defined as smoking at least seven cigarettes per day on average over the week before and 300 cigarettes in the year before each annual interview. Incident asthma was defined using new cases of physician-diagnosed asthma. MEASUREMENTS AND MAIN RESULTS: Regular smoking was associated with increased risk of new-onset asthma. Children who reported smoking 300 or more cigarettes per year had a relative risk (RR) of 3.9 (95% confidence interval [95% CI], 1.7-8.5) for new-onset asthma compared with nonsmokers. The increased risk from regular smoking was greater in nonallergic than in allergic children. Regular smokers who were exposed to maternal smoking during gestation had the largest risk from active smoking (RR, 8.8; 95% CI, 3.2-24.0). CONCLUSIONS: Regular smoking increased risk for asthma among adolescents, especially for nonallergic adolescents and those exposed to maternal smoking during the in utero period.

Adolescent↗

PubMed2006

Health effects of the 2003 Southern California wildfires on children.

RATIONALE: In late October 2003, Southern California wildfires burned more than 3,000 km2. The wildfires produced heavy smoke that affected several communities participating in the University of Southern California Children's Health Study (CHS). OBJECTIVES: To study the acute effects of fire smoke on the health of CHS participants. METHODS: A questionnaire was used to assess smoke exposure and occurrence of symptoms among CHS high-school students (n = 873; age, 17-18 yr) and elementary-school children (n = 5,551; age, 6-7 yr), in a total of 16 communities. Estimates of particulate matter (PM10) concentrations during the 5 d with the highest fire activity were used to characterize community smoke level. MAIN RESULTS: All symptoms (nose, eyes, and throat irritations; cough; bronchitis; cold; wheezing; asthma attacks), medication usage, and physician visits were associated with individually reported exposure differences within communities. Risks increased monotonically with the number of reported smoky days. For most outcomes, reporting rates between communities were also associated with the fire-related PM10 levels. Associations tended to be strongest among those without asthma. Individuals with asthma were more likely to take preventive action, such as wearing masks or staying indoors during the fire. CONCLUSIONS: Exposure to wildfire smoke was associated with increased eye and respiratory symptoms, medication use, and physician visits.

Adolescent↗

PubMed2006

Associations of tumor necrosis factor G-308A with childhood asthma and wheezing.

RATIONALE: Tumor necrosis factor (TNF) mediates a spectrum of airway inflammatory responses, including those to air pollutants, and is an asthma candidate gene. One TNF promoter variant (G-308A) affects expression of TNF and has been associated with inflammatory diseases; however, studies of asthma have been inconsistent. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the -308 TNF polymorphism with asthma may vary by ozone exposure and variants of oxidant defense genes glutathione-S-transferase (GST) M1 and GSTP1. OBJECTIVES: To investigate the association of TNF G-308A with asthma and wheezing and to determine whether these associations vary with ozone exposure and GSTM1 and GSTP1 genotype. METHODS: We studied associations of TNF-308 genotype with lifetime and current wheezing and asthma among 3,699 children in the Children's Health Study. We examined differences in associations with community ozone and by GSTM1 null and GSTP1 105 Ile/Val (A105G) genotype. RESULTS: Children with TNF-308 GG had decreased risk of asthma (odds ratio, 0.8; 95% confidence interval, 0.7-0.9) and lifetime wheezing (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). The protective effects of GG genotype on wheezing outcomes were of greater magnitude in lower compared with higher ozone communities. These findings were replicated in the two cohorts of fourth-grade children recruited in 1993 and 1996. The reduction of the protective effect from the -308 GG genotype with higher ozone exposure was most marked in the GSTM1 null and GSTP1 Ile/Ile groups. CONCLUSIONS: The TNF-308 GG genotype may have a protective role in asthma pathogenesis, depending on airway oxidative stress levels.

Adolescent↗

PubMed2006

Endogenous and exogenous sex steroid hormones and asthma and wheeze in young women.

BACKGROUND: Emerging evidence suggests that both endogenous and exogenous sex steroid hormones may influence the occurrence of asthma and wheeze among women. OBJECTIVE: We investigated the associations between exogenous sex hormone (oral contraceptive [OC]) use and wheezing in young women with and without asthma history. To investigate the role of endogenous sex hormones, we examined the association between age at menarche and the development of asthma after puberty. METHODS: We conducted a study among 905 women who had undergone menarche. Subjects were between 13 and 28 years of age and had participated in the Children's Health Study. RESULTS: In women without asthma, OC use was associated with higher risk of current wheeze (odds ratio [OR], 1.75; 95% CI, 1.15-2.65). In contrast, OC use was associated with a markedly reduced prevalence of current wheeze in women with a history of asthma (OR, 0.18; 95% CI, 0.06-0.56; P value for interaction = .003). These associations showed significant trends with duration of OC use. Age at menarche was associated with new-onset asthma after puberty. Compared with women who had menarche after age 12 years, women with menarche before age 12 years had a 2.08-fold (95% CI, 1.05-4.12) higher risk of asthma after puberty. CONCLUSION: Both endogenous and exogenous sex steroid hormones affect asthma and wheeze occurrences in young women. CLINICAL IMPLICATIONS: Because women have higher asthma risk after puberty, and OC use is common among young women, clinicians may inform women with asthma about the potential effects of OC on asthma-related respiratory symptoms.

Adolescent↗

PubMed2005

Pre-diagnosis physical activity and mammographic density in breast cancer survivors.

PURPOSE: To investigate the association between physical activity (PA) and mammographic density in the year before diagnosis in a population-based sample of 474 women diagnosed with stage 0-IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study. METHODS: We collected information on PA during an interview administered at a baseline visit scheduled within the first year after diagnosis. Participants recalled the type, duration, and frequency of different PAs for the year prior to their diagnosis. Dense area and percent density were estimated, from mammograms imaged approximately 1 year before diagnosis, as a continuous measure using a computer-assisted software program. Analysis of covariance methods were used to obtain mean density across PA tertiles adjusted for confounders. We stratified analyses by menopausal status and body mass index (BMI) because these factors strongly influence density. RESULTS: We observed a statistically significant decline in mammographic dense area (p for trend = 0.046) and percent density (p for trend = 0.026) with increasing level of sports/recreational PA in postmenopausal women with a BMI > or = 30 kg/m2. Conversely, in premenopausal women with a BMI < 30 kg/m2, we observed a statistically significant increase in percent density with increasing level of sports/recreational PA (p for trend = 0.037). CONCLUSIONS: Both mammographic dense area and percent density are inversely related to level of sports/recreational PA in obese postmenopausal women. Increasing PA among obese postmenopausal women may be a reasonable intervention approach to reduce mammographic density.

Adult↗

PubMed2005

A testing framework for identifying susceptibility genes in the presence of epistasis.

An efficient testing strategy called the "focused interaction testing framework" (FITF) was developed to identify susceptibility genes involved in epistatic interactions for case-control studies of candidate genes. In the FITF approach, likelihood-ratio tests are performed in stages that increase in the order of interaction considered. Joint tests of main effects and interactions are performed conditional on significant lower-order effects. A reduction in the number of tests performed is achieved by prescreening gene combinations with a goodness-of-fit chi2 statistic that depends on association among candidate genes in the pooled case-control group. Multiple testing is accounted for by controlling false-discovery rates. Simulation analysis demonstrated that the FITF approach is more powerful than marginal tests of candidate genes. FITF also outperformed multifactor dimensionality reduction when interactions involved additive, dominant, or recessive genes. In an application to asthma case-control data from the Children's Health Study, FITF identified a significant multilocus effect between the nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase gene (NQO1), myeloperoxidase gene (MPO), and catalase gene (CAT) (unadjusted P = .00026), three genes that are involved in the oxidative stress pathway. In an independent data set consisting primarily of African American and Asian American children, these three genes also showed a significant association with asthma status (P = .0008).

Black or African American↗

PubMed2005

Mode of delivery is associated with asthma and allergy occurrences in children.

PURPOSE: A growing body of evidence indicates that perinatal factors modulate immune development and thereby may affect childhood asthma risk. In this study, we examined the associations between birth by cesarean section (C-section) and atopic disease occurrence in childhood. METHODS: Subjects were born in California between 1975 and 1987 and were 8 to 17 years old during their enrollment in the Children's Health Study. Our analysis was restricted to 3464 children born at or after 37 weeks of gestation with a birth weight of 2500 g or greater based on birth certificate data. Information about sociodemographic factors, reported physician-diagnosed asthma, and other atopic diseases was obtained by using a self-administered structured questionnaire. Logistic regression models were fitted to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Children born by C-section were at increased risk for asthma (OR, 1.33; 95% CI, 1.01-1.75), hay fever (OR, 1.57; 95% CI, 1.24-1.99), and allergy (OR, 1.26; 95% CI, 1.03-1.53) compared with those born vaginally. Risk associated with C-section was the same for children regardless of family history of asthma or allergy. CONCLUSION: We conclude that birth by C-section or processes associated with it may increase the risk for atopic disease in childhood.

Adolescent↗

PubMed2005

Gene promoter methylation in plasma and sputum increases with lung cancer risk.

PURPOSE: Lung cancer is the leading cause of cancer mortality in the United States, due in part to the lack of a validated and effective screening approach for early detection. The prevalence for methylation of seven and three genes was examined in DNA from sputum and plasma, respectively, from women at different risk for lung cancer. EXPERIMENTAL DESIGN: Lung cancer survivors (n = 56), clinically cancer-free smokers (n = 121), and never smokers (n = 74) comprised the study population. Plasma was collected from all three groups, whereas sputum was collected from lung cancer survivors and smokers. RESULTS: Methylation was detected in plasma DNA from 10 of 74 women who never smoked. Prevalence for methylation of the p16 gene in plasma was highest in lung cancer survivors. Lung cancer survivors showed a significant increase in the odds of having at least one or more genes methylated in plasma (odds ratio, 3.6; 95% confidence interval, 1.9-9.1) than never smokers. The prevalence for methylation of the O(6)-methylguanine-DNA methyltransferase, ras effector homologue 1, death associated protein kinase, and PAX5alpha genes in sputum was significantly higher in lung cancer survivors compared with smokers. Lung cancer survivors had 6.2-fold greater odds (95% confidence interval, 2.1-18.5) for methylation of three or more genes in sputum compared with smokers. Methylation was more commonly detected in sputum than plasma for O(6)-methylguanine-DNA methyltransferase and ras effector homologue 1, but not p16, in lung cancer survivors. CONCLUSION: Concomitant methylation of multiple gene promoters in sputum is strongly associated with lung cancer risk.

Adult↗

PubMed2005

TNF-308 modifies the effect of second-hand smoke on respiratory illness-related school absences.

RATIONALE: Exposure to second-hand smoke (SHS) has been associated with increased risk of respiratory illness in children including respiratory illness-related school absences. The role of genetic susceptibility in risk for adverse effects from SHS has not been extensively investigated in children. OBJECTIVE: To determine whether the tumor necrosis factor (TNF) G-308A genotype influences the risk for respiratory illness-related school absences associated with SHS exposure. METHODS: Incident school absences were collected, using an active surveillance system, between January and June 1996, as part of the Air Pollution and Absence Study, a prospective cohort study nested in the Children's Health Study. Buccal cells and absence reports were collected on 1,351 students from 27 elementary schools in California. MEASUREMENTS AND MAIN RESULTS: Illness-related school absences were classified as nonrespiratory and respiratory illness-related, which were further categorized into upper or lower respiratory illness-related absences based on symptoms. The effect of SHS exposure on respiratory illness-related absences differed by TNF genotype (p interaction, 0.02). In children possessing at least one copy of the TNF-308 A variant, exposure to two or more household smokers was associated with a twofold risk of a school absence due to respiratory illness (relative risk, 2.13; 95% confidence interval, 1.34, 3.40) and a fourfold risk of lower respiratory illness-related school absence (relative risk, 4.15; 95% confidence interval, 2.57, 6.71) compared with unexposed children homozygous for the common TNF-308 G allele. CONCLUSIONS: These results indicate that a subgroup of genetically susceptible children are at substantially greater risk of respiratory illness if exposed to SHS.

Absenteeism↗

PubMed2005

Intercellular adhesion molecule-1 and childhood asthma.

We investigated the role of intercellular adhesion molecule-1 in childhood asthma by examining associations of functional variants at codons 29 (A --> T), 241 (G --> A), and 469 (A --> G) in Children's Health Study participants. Among African-Americans, 469G carriers had lower risk for asthma (ever asthma OR = 0.4, 95% CI 0.2-0.9) but increased risk among 29T carriers (early onset active asthma OR = 2.2, 95% CI 1.0-4.9). Protective associations with the 241A allele were observed among non-Hispanic and Hispanic whites (ever asthma OR = 0.7, 95% CI 0.6-0.9; early onset active asthma OR = 0.5, 95% CI 0.4-0.8), and these associations were not confounded by population stratification. To gauge the potential impact of confounding by population stratification, we performed analyses by ethnic group and in an independent family-based sample. Regional associations were stable across analyses. Haplotype associations of the four common haplotypes (29A/241G/469A, AGG, TGA, and AAG) with asthma showed that Hispanics with the AAG haplotype had lower asthma risk compared to carriers of two copies of AGA haplotype (OR = 0.6, 95% CI 0.4-0.9). Among non-Hispanic whites, the AAG haplotype was associated with reduced risk for active asthma. For African-Americans, who had a low frequency of the AAG haplotype, carrying one copy of the AGG haplotype was associated with a lower risk of asthma (OR = 0.3, 95% CI 0.1-0.8), as compared with two copies of the AGA haplotype. Consistent with information on variant function, the 241A and 469G variants may indicate haplotypes that are associated with reduced risk for asthma.

Adolescent↗

PubMed2005

Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers.

The prevalence of methylation of the p16, DAPK and RASSF1A genes was investigated in lung adenocarcinoma from smokers, former uranium miners and never smokers. The association between a common genetic alteration in adenocarcinoma, mutation of the K-ras gene and methylation of these genes, as well as survival was examined. Adenocarcinomas from 157 smokers, 46 never smokers and 34 former uranium miners were evaluated for methylation of the p16, DAPK and RASSF1A genes using the methylation-specific PCR assay. Comparisons were also made to prevalences of methylation of the MGMT gene and mutation of the K-ras gene previously examined in these tumors. The prevalence of methylation for all genes was similar between adenocarcinomas from smokers and never smokers, although the prevalence for methylation of the p16 gene tended to be higher in smokers compared to never smokers. A significantly higher prevalence for p16 methylation was seen in central vs. peripheral lung tumors. At least 1 gene was methylated in 35% of stage I tumors, whereas 2 and >/=3 genes were methylated in 40% and 16% of tumors, respectively. Methylation of all genes was independent of K-ras mutation, whereas methylation of the DAPK and RASSF1A genes was positively associated. Environmental tobacco smoke, the strongest lung cancer risk factor among never smokers, induces adenocarcinoma in part through inactivation of the p16, DAPK and RASSF1A genes. Adenocarcinomas may develop through 2 distinct processes: multiple gene inactivations through promoter hypermethylation and activation of the K-ras gene.

Adenocarcinoma↗

PubMed2005

Changes in body fat and weight after a breast cancer diagnosis: influence of demographic, prognostic, and lifestyle factors.

PURPOSE: Obese women and women who gain weight after a breast cancer diagnosis are at a greater risk for breast cancer recurrence and death compared with lean women and women who do not gain weight after diagnosis. In this population-based study, we assessed weight and body fat changes from during the first year of diagnosis to during the third year after diagnosis, and whether any changes in weight and body fat varied by demographic, prognostic, and lifestyle factors in 514 women with incident Stage 0-IIIA breast cancer. METHODS: Patients were participants in the Health, Eating, Activity, and Lifestyle (HEAL) study. Weight and body fat (via dual-energy x-ray absorptiometry scans) were measured during the baseline visit and 2 years later at a follow-up visit. Analysis of covariance methods were used to obtain mean weight and body fat changes adjusted for potential cofounders. RESULTS: Women increased their weight and percent body fat by 1.7 +/- 4.7 kg and 2.1% +/- 3.9%, respectively, from during their first year of diagnosis to during their third year of diagnosis. A total of 68% and 74% of patients gained weight and body fat, respectively. Greater increases in weight were observed among women diagnosed with a higher disease stage, younger age, being postmenopausal, and women who decreased their physical activity from diagnosis to up to 3 years after diagnosis (P for trend < .05). CONCLUSION: Weight and body fat increased in the postdiagnosis period. Future research should focus on the effect of physical activity on weight and fat loss and breast cancer prognosis.

Adipose Tissue↗

PubMed2005

5-year urinary and sexual outcomes after radical prostatectomy: results from the prostate cancer outcomes study.

PURPOSE: Prior studies of postoperative outcomes following radical prostatectomy have been limited by selection bias and short-term followup. In this study we assessed temporal changes in urinary and sexual function up to 5 years following radical prostatectomy in a population based cohort. MATERIALS AND METHODS: A sample of 1,288 men with localized prostate cancer who underwent radical prostatectomy and completed a baseline survey within 6 to 12 months of diagnosis were included in the analysis. Two and 5-year functional and quality of life data were collected, as was information on the use of erectile aids. Temporal functional changes and potentially confounding or modifying factors were assessed using longitudinal regression models. RESULTS: Of these men 14% reported frequent urinary leakage or no urinary control 60 months after diagnosis, which was slightly higher than the 10% reporting incontinence at 24 months (p = 0.007). At 60 months 28% of the men had erections firm enough for intercourse compared with 22% at 24 months (p = 0.003). Sildenafil was the most commonly used erectile aid (43% ever used) and 45% of users reported that it helped "somewhat" or "a lot." CONCLUSIONS: Urinary and sexual dysfunction were common 5 years following radical prostatectomy in this large, community based cohort of prostate cancer survivors. While a small minority of subjects experienced changes in urinary or sexual function between years 2 and 5 after prostatectomy, functional outcomes remained relatively stable in the majority of participants.

Adult↗

PubMed2005

Treatment of erectile dysfunction following therapy for clinically localized prostate cancer: patient reported use and outcomes from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study.

PURPOSE: Erectile dysfunction (ED) persists for years following curative therapies for clinically localized prostate cancer. We report use and treatment outcomes in a 5-year interval in a population based cohort from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study. MATERIALS AND METHODS: A sample of 1,977 men with localized prostate cancer who received external beam radiation therapy or radical prostatectomy in 1994 to 1995 were surveyed for 5 outcome measures of ED treatment, namely treatment, perceived helpfulness, erectile sufficiency, sexual activity frequency and erection maintenance. Subjects were surveyed 6, 12, 24 and 60 months after prostate cancer diagnosis. RESULTS: Overall 50.5% of men ever used ED treatment. The use of ED treatments increased during the study course. Subject age, regular sexual partner and baseline sexual activity were factors positively associated with ED treatments. While it was used uncommonly (1.9%), a penile prosthesis was perceived as the most helpful ED treatment (helped a lot in 52% of respondents). Sildenafil helped a lot in 12% of respondents. Erectile fullness, erection maintenance and sexual activity frequency were modestly improved in men using ED treatment compared with those in men not using ED treatment. CONCLUSIONS: Approximately half of the patients in this population based cohort of men used ED treatment during the 5 years following prostate cancer diagnosis. Men using ED treatments had modest improvement in sexual function compared with men that in who did not receive ED treatment at 60 months. More effective treatments for ED following local therapy for prostate cancer are needed.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2005

Relationship of obesity and physical activity with C-peptide, leptin, and insulin-like growth factors in breast cancer survivors.

INTRODUCTION: Obese and physically inactive breast cancer patients may have poorer survival compared with lighter weight and more active women. Several obesity-related and physical activity-related hormones and peptides may explain this association, including insulin, leptin, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Few studies have examined the associations between obesity, physical activity, and these hormones/peptides among breast cancer survivors. PURPOSE: To determine whether obesity and physical activity are associated with insulin, IGFs, and leptin levels in a population-based sample of 710 women diagnosed with in situ to stage IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study. METHODS: We collected a blood sample and information on physical activity among women diagnosed 2 to 3 years earlier using an interview-administered questionnaire. Trained staff measured weight. C-peptide, leptin, and IGFs were assayed by RIA. Mean hormone levels within body mass index and physical activity categories were adjusted for confounders using analysis of covariance methods. RESULTS: We observed higher C-peptide (P for trend = 0.0001) and leptin (P for trend = 0.0001) levels and lower IGF-I levels (P for trend = 0.0001) with higher levels of body mass index. We observed lower C-peptide (P for trend = 0.001) and leptin (P for trend = 0.001) levels and higher IGF-I (P for trend = 0.0037) and IGF-binding protein-3 (P for trend = 0.055) levels with higher levels of physical activity. CONCLUSIONS: Increasing physical activity and decreasing body fat may be a reasonable intervention approach toward changing insulin and leptin, thereby potentially influencing breast cancer prognosis.

Adult↗

PubMed2005

Birth outcomes and prenatal exposure to ozone, carbon monoxide, and particulate matter: results from the Children's Health Study.

Exposures to ambient air pollutants have been associated with adverse birth outcomes. We investigated the effects of air pollutants on birth weight mediated by reduced fetal growth among term infants who were born in California during 1975-1987 and who participated in the Children's Health Study. Birth certificates provided maternal reproductive history and residence location at birth. Sociodemographic factors and maternal smoking during pregnancy were collected by questionnaire. Monthly average air pollutant levels were interpolated from monitors to the ZIP code of maternal residence at childbirth. Results from linear mixed-effects regression models showed that a 12-ppb increase in 24-hr ozone averaged over the entire pregnancy was associated with 47.2 g lower birth weight [95% confidence interval (CI), 27.4-67.0 g], and this association was most robust for exposures during the second and third trimesters. A 1.4-ppm difference in first-trimester carbon monoxide exposure was associated with 21.7 g lower birth weight (95% CI, 1.1-42.3 g) and 20% increased risk of intrauterine growth retardation (95% CI, 1.0-1.4). First-trimester CO and third-trimester O3 exposures were associated with 20% increased risk of intrauterine growth retardation. A 20-microg/m3 difference in levels of particulate matter < or = 10 microm in aerodynamic diameter (PM10) during the third trimester was associated with a 21.7-g lower birth weight (95% CI, 1.1-42.2 g), but this association was reduced and not significant after adjusting for O3. In summary, O3 exposure during the second and third trimesters and CO exposure during the first trimester were associated with reduced birth weight.

Adult↗