Showing papers by "Frank E. Speizer published in 2004"

A Prospective Study of Sleep Duration and Mortality Risk in Women

Abstract: adjusting for age, smoking, alcohol, exercise, depression, snoring, obesity, and history of cancer and cardiovascular disease, sleeping less than 6 hours or more than 7 hours remained associated with an increased risk of death. The relative mortality risk for sleeping 5 hours or less was 1.15 (95% confidence interval [CI], 1.02-1.29) for 6 hours, 1.01 (95% CI, 0.941.08), for 7 hours, 1.00 (reference group), for 8 hours, 1.12 (95% CI, 1.051.20), and for 9 or more hours 1.42 (95% CI, 1.27-1.58). Conclusions: These results confirm previous findings that mortality risk in women is lowest among those sleeping 6 to 7 hours. Further research is needed to understand the mechanisms by which short and long sleep times can affect health.

Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies.

Abstract: BACKGROUND: Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent. OBJECTIVE: To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association. DESIGN: Pooled analysis of primary data from 8 cohort studies in 5 countries. SETTING: North America and Europe. PARTICIPANTS: 489,979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline. MEASUREMENTS: Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire. RESULTS: During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages. LIMITATIONS: The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use. CONCLUSIONS: A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.

Lung Cancer Rates in Men and Women With Comparable Histories of Smoking

Abstract: Background: Recent case-control studies suggest that, given equal smoking exposure, women may have a higher relative risk of developing lung cancer than men. Despite prospective data that conflict with this hypothesis, mechanistic studies to find a biologic basis for a sex difference continue. Methods: We addressed the hypothesis directly by analyzing prospective data from former and current smokers in two large cohorts-the Nurses' Health Study of women and the Health Professionals Follow-up Study of men. We calculated incidence rates and hazard ratios of lung cancer in women compared with men, adjusting for age, number of cigarettes smoked per day, age at start of smoking, and time since quitting, using Cox proportional hazards models. We also reviewed published results from prospective analyses. Results: From 1986 through 2000, 955 and 311 primary lung cancers were identified among 60 296 women and 25 397 men, respectively, who ranged in age from 40 to 79 years. Incidence rates per 100 000 person-years for women and men were 253 and 232, respectively, among current smokers and 81 and 73, respectively, among former smokers. The hazard ratio in women ever smokers compared with men was 1.11 (95% confidence interval = 0.95 to 1.31). Six published prospective cohort studies allowed assessment of comparative susceptibility to lung cancer by sex. None supported an excess risk of lung cancer for women. Conclusions: Women do not appear to have a greater susceptibility to lung cancer than men, given equal smoking exposure. Research should be focused on enhancing preventive interventions for all.

Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women.

Abstract: OBJECTIVE —Inflammation plays a key role in chronic obstructive pulmonary disease (COPD) and asthma. Increasing evidence points toward a role of inflammation in the pathogenesis of type 2 diabetes. We wanted to determine the relation of COPD and asthma with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS —The Nurses’ Health Study is a prospective cohort study. From 1988–1996, 103,614 female nurses were asked biennially about a physician diagnosis of emphysema, chronic bronchitis, asthma, and diabetes. RESULTS —During 8 years of follow-up, we documented a total of 2,959 new cases of type 2 diabetes. The risk of type 2 diabetes was significantly higher for patients with COPD than those without (multivariate relative risk 1.8, 95% CI 1.1–2.8). By contrast, the risk of type 2 diabetes among asthmatic patients was not increased (1.0, 0.8–1.2). The asthma results remained nonsignificant even when we evaluated diabetes risk by duration of asthma exposure. CONCLUSIONS —Our findings suggest that COPD may be a risk factor for developing type 2 diabetes. Differences in the inflammation and cytokine profile between COPD and asthma might explain why COPD, but not asthma, is associated with increased risk of type 2 diabetes.

The transforming growth factor-β1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD)

Abstract: Although cigarette smoking is the primary environmental risk factor, genetic risk factors likely influence the development of chronic obstructive pulmonary disease (COPD). Linkage analysis between short-tandem repeat markers on chromosome 19 and COPD phenotypes was followed by association analysis of single nucleotide polymorphisms in a gene on chromosome 19q [transforming growth factor-beta1 (TGFB1)] and COPD phenotypes in a family-based sample and a case-control study (cases with severe COPD and control subjects with significant history of smoking but no COPD). Stratification by smoking status substantially improved the evidence of linkage to chromosome 19q for COPD phenotypes. Among former and current smokers in the Boston Early-Onset COPD Study, there was significant evidence of linkage between chromosome 19q and pre-bronchodilator (pre-BD) FEV(1) (LOD=3.30) and suggestive evidence of linkage between chromosome 19q and other COPD phenotypes. In these families, a SNP in the promoter region of TGFB1 (rs2241712) and two SNPs in the 3' genomic region of TGFB1 (rs2241718 and rs6957) were significantly associated with pre- and post-BD FEV(1) (P<0.05). Among smokers in the COPD cases and control subjects, two SNPs in the promoter region of TGFB1 (rs2241712 and rs1800469) and one SNP in exon 1 of TGFB1 (rs1982073) were significantly associated with COPD (P

Lung cancer in railroad workers exposed to diesel exhaust.

Abstract: Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30-1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort. Key words: diesel exhaust, lung cancer, occupational exposure.

Depressive symptoms and risk of type 2 diabetes in women

Abstract: OBJECTIVE —To explore the relationship between depressive symptoms and incidence of type 2 diabetes in women. RESEARCH DESIGN AND METHODS —We conducted an analysis of 72,178 female nurses aged 45–72 years who did not have diagnosed diabetes and who answered the Medical Outcomes Study 36-Item Short-Form Health Status Survey (SF-36) at baseline in 1992. We calculated relative risks (RR) of type 2 diabetes for women with presence of depressive symptoms (i.e., Five-Item Mental Health Index [MHI-5] score >52). RESULTS —During 4 years of follow-up (282,317 person-years), 973 incident cases of type 2 diabetes were documented. Age-adjusted RR of developing type 2 diabetes for women with presence of depressive symptoms was 1.55 (95% CI 1.27–1.90). Additional adjustment for BMI resulted in a RR of developing type 2 diabetes of 1.36 (1.11–1.67). The multivariate RR of developing type 2 diabetes was 1.22 (1.00–1.50). After excluding women diagnosed with diabetes between 1992 and 1994, 472 incident cases of type 2 diabetes were documented for the follow-up period from 1994 to 1996 (148,889 person-years). The multivariate RR of developing type 2 diabetes for women with depressive symptoms was 1.29 (0.96–1.72). CONCLUSIONS —Our data suggest that depressive symptoms are associated with a modest increase in the risk of type 2 diabetes.

Prospective study of postmenopausal hormone use and newly diagnosed asthma and chronic obstructive pulmonary disease.

Abstract: Background Female reproductive hormones appear to influence asthma, although data are conflicting, and may modulate development of chronic obstructive pulmonary disease (COPD). Therefore, in a prospective cohort study, we evaluated whether postmenopausal hormone use was associated with an increased rate of newly diagnosed asthma and, separately, newly diagnosed COPD. Methods Postmenopausal hormone use was assessed by questionnaire biennially from 1976 onward. New physician diagnoses of asthma or COPD were reported on questionnaires from 1988 to 1996 and confirmed in 1998 using supplementary questionnaires. Grades of diagnostic certainty were established from reports of medication use and pulmonary function using validated definitions. Results During 546 259 person-years of follow-up, current use of estrogen alone was associated with an increased rate of asthma (multivariate rate ratio, 2.29; 95% confidence interval [CI], 1.59-3.29) compared with those who never used hormones. Current users of estrogen plus progestin had a similarly increased rate of newly diagnosed asthma. Rate ratios increased with certainty of diagnosis of asthma. In contrast, rates of newly diagnosed COPD were the same among hormone users and nonusers (multivariate rate ratio, 1.05; 95% CI, 0.80-1.37). Conclusions Postmenopausal hormone use was associated with an increased rate of newly diagnosed asthma but not newly diagnosed COPD. Female reproductive hormones may contribute to the onset of asthma among adult women, but do not appear to hasten the development of COPD.

Prospective study of acetaminophen use and newly diagnosed asthma among women.

Abstract: Acetaminophen decreases glutathione levels in the lung, which may predispose to oxidative injury and bronchospasm. Acetaminophen use has been associated with asthma in cross-sectional studies and a birth cohort. We hypothesized that acetaminophen use would be associated with newly diagnosed adult-onset asthma in the Nurses' Health Study, a prospective cohort study of 121,700 women. Participants were first asked about frequency of acetaminophen use in 1990. Cases with asthma were defined as those with a new physician diagnosis of asthma between 1990 and 1996 plus reiteration of the diagnosis and controller medication use. Proportional hazard models included age, race, socioeconomic status, body mass index, smoking, other analgesic use, and postmenopausal hormone use. During 352,719 person-years of follow-up, 346 participants reported a new physician diagnosis of asthma meeting diagnostic criteria. Increasing frequency of acetaminophen use was positively associated with newly diagnosed asthma (p for trend = 0.006). The multivariate rate ratio for asthma for participants who received acetaminophen for more than 14 days per month was 1.63 (95% confidence interval, 1.11-2.39) compared with nonusers. It would be premature to recommend acetaminophen avoidance for patients with asthma, but further research on pulmonary responses to acetaminophen is necessary to confirm or refute these findings and to identify subgroups whose asthma may be modified by acetaminophen.

Association between air pollution exposure and exhaled nitric oxide in an elderly population

Abstract: Background: Animal models suggest that the cardiovascular effects of air pollution result in part from inflammation caused by proinflammatory mediators originating in the lung. In a human study of the cardiovascular effects of air pollution, we aimed to evaluate the potential association between air pollution levels and the fraction of exhaled nitric oxide (Fe NO ), a non-invasive measure of airway inflammation. Methods: Breath samples were collected weekly between September and December 2000 in a community based group of elderly subjects (median age 70.7 years) in Steubenville, Ohio. The samples were analysed for NO. Air pollution levels were measured concurrently at a central site monitor. Results: An increase in the 24 hour average PM 2.5 concentration of 17.7 µg/m 3 was associated with an increase in Fe NO of 1.45 ppb (95% CI 0.33 to 2.57) in models adjusted for subject, week of study, day of the week, hour of the day, ambient barometric pressure, temperature, and relative humidity. This represents a change of approximately 15% compared with the mean Fe NO in the cohort (9.9 ppb). A significant association was also observed for a 24 hour moving average of ambient NO (0.83 ppb increase, 95% CI 0.26 to 1.40). In two-pollutant models, the magnitude and precision of the PM 2.5 effect was not reduced and the ambient NO effect was no longer significant. The associations between Fe NO and PM 2.5 were significantly higher in subjects with a doctor’s diagnosis of COPD (p value for interaction = 0.03). Conclusions: Ambient pollution may lead to airway inflammation as measured by Fe NO . These subclinical inflammatory changes may be an important step in the pathogenesis of the cardiopulmonary effects induced by exposure to air pollution.

Familial aggregation of FEF(25-75) and FEF(25-75)/FVC in families with severe, early onset COPD.

Abstract: Background: The Boston Early-Onset COPD study showed that current or ex-smoking first degree relatives of severe early onset COPD probands have significantly lower forced expiratory volume in 1 second (FEV 1 ) and FEV 1 /forced vital capacity (FVC) values than current or ex-smoking control subjects, which suggests the existence of genetic risk factors for the development of COPD in response to cigarette smoking. We hypothesised that first degree relatives of early onset COPD probands may also have lower values of spirometric parameters such as forced expiratory flow at the mid-portion of forced vital capacity (FEF 25–75 ) and FEF 25–75 /FVC. Methods: Using generalised estimating equations, FEF 25–75 and FEF 25–75 /FVC were analysed in 333 first degree relatives of probands with severe early onset COPD and 83 population based controls; analyses were also performed on data stratified by smoking status. Narrow sense heritability estimates were calculated using a variance component approach. Results: Significantly lower FEF 25–75 and FEF 25–75 /FVC were observed in smoking (FEF 25–75 : β −0.788 l/s (95% CI −1.118 to −0.457), FEF 25–75 /FVC: β −20.4% (95% CI −29.3 to −11.6, p 25–75 : β −0.357 l/s (95% CI −0.673 to −0.041, p = 0.0271), FEF 25−75 /FVC: β −9.5% (95% CI −17.1 to −1.9, p = 0.0145)) first degree relatives of early onset COPD probands. Narrow sense heritability estimates for FEF 25–75 ( h 2 = 0.38) and FEF 25–75 /FVC ( h 2 = 0.45) were similar to those for FEV 1 and FEV 1 /FVC. Conclusion: Lower values of FEF 25–75 and FEF 25–75 /FVC in non-smoking first degree relatives of early onset COPD probands than in controls suggest a genetic susceptibility to develop obstructive lung disease, independent of smoking, which is magnified by exposure to deleterious environments as suggested by the further decrements in FEF 25–75 and FEF 25–75 /FVC seen in smoking first degree relatives. FEF 25–75 and FEF 25–75 /FVC have high heritability and are important intermediate phenotypes for inclusion in genetic epidemiological studies of COPD.

Genome-wide linkage of forced mid-expiratory flow in Chronic Obstructive Pulmonary Disease

Abstract: Familial aggregation of forced expiratory flow during the middle half of the FVC (FEF25–75%) and FEF25–75%/FVC has been observed in the Boston Early-Onset Chronic Obstructive Pulmonary Disease Study, but linkage results have not been reported for these phenotypes. An autosomal whole genome-wide linkage scan was performed in 72 pedigrees ascertained through a proband with severe, early-onset chronic obstructive pulmonary disease, and linkage analyses of FEF25–75% and FEF25–75%/FVC were performed using Sequential Oligogenic Linkage Analysis Routines. There was suggestive evidence for linkage of FEF25–75%/FVC with chromosome 2 (LOD 2.60 at 216 cM). In a smokers-only analysis, evidence for linkage was observed for postbronchodilator FEF25–75% with chromosome 12 (LOD 5.03 at 35 cM) and chromosomes 2 and 12 for FEF25–75%/FVC (LOD 4.12 at 221 cM and LOD 3.46 at 35 cM, respectively); in the smokers-only model, evidence for linkage also was robust for FEV1/FVC on chromosome 2 (LOD 4.13 at 229 cM) and FEV1 on chrom...

A prospective study of dietary lactose and ovarian cancer

Abstract: The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each 11-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study.

ARTICLES Lung Cancer Rates in Men and Women With Comparable Histories of Smoking

Abstract: Background: Recent case– control studies suggest that, given equal smoking exposure, women may have a higher relative risk of developing lung cancer than men. Despite prospective data that conflict with this hypothesis, mechanistic studies to find a biologic basis for a sex difference continue. Methods: We addressed the hypothesis directly by analyzing prospective data from former and current smokers in two large cohorts—the Nurses’ Health Study of women and the Health Professionals Follow-up Study of men. We calculated incidence rates and hazard ratios of lung cancer in women compared with men, adjusting for age, number of cigarettes smoked per day, age at start of smoking, and time since quitting, using Cox proportional hazards models. We also reviewed published results from prospective analyses. Results: From 1986 through 2000, 955 and 311 primary lung cancers were identified among 60 296 women and 25 397 men, respectively, who ranged in age from 40 to 79 years. Incidence rates per 100 000 person-years for women and men were 253 and 232, respectively, among current smokers and 81 and 73, respectively, among former smokers. The hazard ratio in women ever smokers compared with men was 1.11 (95% confidence interval 0.95 to 1.31). Six published prospective cohort studies allowed assessment of comparative susceptibility to lung cancer by sex. None supported an excess risk of lung cancer for women. Conclusions: Women do not appear to have a greater susceptibility to lung cancer than men, given equal smoking exposure. Research should be focused on enhancing preventive interventions for all. [J Natl Cancer Inst 2004;96:826 –34]