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Gallagher L.G.,University of Washington | Rosenblatt K.A.,University of Illinois at Urbana - Champaign | Ray R.M.,Fred Hutchinson Cancer Research Center | Li W.,Fred Hutchinson Cancer Research Center | And 5 more authors.
Cancer Causes and Control | Year: 2013

Purpose: Hormonal factors may play a role in the development of lung cancer in women. This study examined the relationship between lung cancer and reproductive factors in a large cohort of women, most of whom never smoked (97 %). Methods: A cohort of 267,400 female textile workers in Shanghai, China, enrolled in a trial of breast self-examination provided information on reproductive history, demographical factors, and cigarette smoking at enrollment in 1989-91. The cohort was followed until July of 2000 for incidence of lung cancer; 824 cases were identified. Hazard ratios (HR) and 95 % confidence intervals (CI) associated with selected reproductive factors were calculated using Cox proportional hazards modeling, adjusting for smoking, age, and also parity when relevant. Results: Nulliparous women were at increased risk compared to parous women (HR = 1.33, 95 % CI 1.00-1.77). Women who had gone through menopause at baseline were at increased risk compared to women of the same age who were still menstruating. Risk was higher in women with a surgical menopause (HR = 1.64, 95 % CI 0.96-2.79) than in those with a natural menopause (HR = 1.35, 95 % CI 0.84-2.18), and risk was highest in those postmenopausal women with a hysterectomy and bilateral oophorectomy at baseline (HR = 1.39, 95 % CI 0.96-2.00), although the risk estimates were not statistically significant. Conclusions: These results support experimental data that demonstrate a biological role for hormones in lung carcinogenesis. © 2013 Springer Science+Business Media Dordrecht.


Dijkstra S.C.,Fred Hutchinson Cancer Research Center | Dijkstra S.C.,Wageningen University | Lampe J.W.,Fred Hutchinson Cancer Research Center | Ray R.M.,Fred Hutchinson Cancer Research Center | And 10 more authors.
Journal of Nutrition | Year: 2010

Fibroadenomas are the most common benign breast condition among women and account for up to 50% of all breast biopsies being performed. Although considered a benign condition, fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies. Dietary factors may influence benign fibrocystic breast conditions, but little is known of their association with fibroadenomas. We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas. Participants were women in a breast self-examination trial in Shanghai, China who were diagnosed with fibroadenomas (n = 258) and 1035 controls. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% CI. Isoflavone concentrations were inversely associated with risk of fibroadenomas. Adjusted OR (95% CI) for the highest versus the lowest quartile of plasma concentration were 0.36 (0.16-0.79; P-trend < 0.001) for daidzein and 0.39 (0.19-0.84; P-trend = 0.010) for genistein. We also observed inverse associations between higher percentages of the RBC (n-3) fatty acids, eicosapentaenoic acid (EPA) ([0.38 (0.19-0.77); P-trend = 0.007] and docosapentaenoic acid (DPA) [0.32 (0.15-0.70); P-trend = 0.024], and fibroadenoma risk. Circulating concentrations of carotenoids, vitamin C, retinol, and ferritin were not associated with fibroadenoma risk. The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas. © 2010 American Society for Nutrition.


Frankenfeld C.L.,George Mason University | Lampe J.W.,Fred Hutchinson Cancer Research Center | Lampe J.W.,University of Washington | Shannon J.,Oregon Health And Science University | And 7 more authors.
Public Health Nutrition | Year: 2012

Objective To evaluate the validity of fruit and vegetable intakes as it relates to plasma carotenoid and vitamin C concentrations in Chinese women, using three classification schemes. Design Intakes were calculated using an interviewer-administered FFQ. Fruits and vegetables, botanical groups and high-nutrient groups were evaluated. These three classification schemes were compared with plasma carotenoid and vitamin C concentrations from blood samples collected within 1 week of questionnaire completion.Setting Shanghai, China. Subjects Participants (n 2031) comprised women who had participated in a case-control study of diet and breast-related diseases nested within a randomized trial of breast self-examination among textile workers (n 266 064)Results Fruit intake was significantly (P < 0.05) and positively associated with plasma concentrations of α-tocopherol, β-cryptoxanthin, lycopene, α-carotene, β-carotene, retinyl palmitate and vitamin C. Fruit intake was inversely associated with γ-tocopherol and lutein + zeaxanthin concentrations. Vegetable consumption was significantly and positively associated with γ-tocopherol and β-cryptoxanthin concentrations. Each botanical and high-nutrient group was also significantly associated with particular plasma nutrient concentrations. Fruit and vegetable intakes and most plasma nutrient concentrations were significantly associated with season of interview. Conclusions These results suggest that the manner in which fruits and vegetables are grouped leads to different plasma nutrient exposure information, which may be an important consideration when testing and generating hypotheses regarding disease risk in relation to diet. Interview season should be considered when evaluating the associations of reported intake and plasma nutrients with disease outcomes. © The Authors 2011.


Gallagher L.G.,University of Washington | Li W.,Fred Hutchinson Cancer Research Center | Ray R.M.,Fred Hutchinson Cancer Research Center | Romano M.E.,Brown University | And 5 more authors.
American Journal of Industrial Medicine | Year: 2015

Background: Associations between stomach and esophageal cancer and exposures to dusts, metals, chemicals, and endotoxin in the workplace are not very well understood, particularly in women. Methods: We followed 267,400 female textile workers in Shanghai, China for cancer incidence from 1989 to 2006. Stomach (n=1374) and esophageal (n=190) cancer cases were identified and a comparison subcohort (n=3187) was randomly selected. Cox proportional hazard modeling was used, adjusting for age and smoking. Results: Increasing stomach cancer risk was observed with increasing duration of synthetic fiber dust exposure (p=0.03), although the magnitude of effect was small (20 + years: HR=1.2, 95% CI 1.1-1.4). Trends with endotoxin exposure were modestly inversed for esophageal cancer and increased for stomach cancer, but with little deviation from a null association. Conclusions: Our findings demonstrate that long durations of synthetic fiber dust exposure can increase stomach cancer risk in women, but provide limited support for associations with other textile industry exposures. Am. J. Ind. Med. 58:267-275, 2015. © 2015 Wiley Periodicals, Inc.


Gallagher L.G.,University of Washington | Ray R.M.,Fred Hutchinson Cancer Research Center | Li W.,Fred Hutchinson Cancer Research Center | Psaty B.M.,University of Washington | And 5 more authors.
American Journal of Industrial Medicine | Year: 2012

Background: Exposure to textile fiber dusts, like particulate air pollution, may be associated with cardiovascular disease (CVD) mortality. Bacterial endotoxin, a potent inflammagen found in cotton dust, may be a specific risk factor. Methods: Female textile workers (N=267,400) in Shanghai, China were followed for CVD mortality (1989-2000). Factory exposures were approximated by sector classifications based on materials and processes. Quantitative endotoxin and cotton dust measures were available for a subcohort (n=3,188). Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence interval (CI). Results: Slightly elevated mortality risk for the cotton sector was seen for ischemic stroke (HR=1.12, 95% CI: 0.97-1.31) and hemorrhagic stroke (HR=1.12, 95% CI: 1.02-1.23). Similar hemorrhagic stroke mortality risk was observed in high dust sectors (HR=1.12, 95% CI: 1.02-1.24). No association was observed for ischemic heart disease. Conclusions: Exposures in textile factories may have contributed to CVD mortality among this cohort. The specific components of these exposures that may be harmful are not clear and should be further investigated. © 2012 Wiley Periodicals, Inc.


Applebaum K.M.,Boston University | Applebaum K.M.,Harvard University | Ray R.M.,Fred Hutchinson Cancer Research Center | Astrakianakis G.,University of British Columbia | And 9 more authors.
Occupational and Environmental Medicine | Year: 2013

Introduction Occupational exposure to endotoxin, found in Gram-negative bacteria in organic material, has been associated predominantly with a reduced risk of lung cancer among workers. An inverse exposure- response gradient among women textile workers in Shanghai, China, has been reported previously. In this case-cohort study, we investigated the influence of left truncation, which can itself induce a downward trend, on the observed association. Methods Subjects were enrolled between 1989 and 1991 and followed until 1998. The data were left-truncated as all subjects were hired before baseline. An analysis was performed with 3038 subcohort members and 602 cases of incident lung cancer. To evaluate left truncation, we compared lung cancer rates in those hired longer ago with those hired more recently among unexposed subjects. Cox proportional hazards modelling was used to estimate incident rate ratios (IRRs) and 95% CIs. Results Among those who were never exposed to workplace endotoxin, we compared lung cancer rates in those hired >35 years before enrolment with workers hired =35 years before enrolment and observed a reduced risk in the former group, IRR=0.74, 95% CI (0.51 to 1.07). After accounting for this downward bias from left truncation, the reduced risk associated with endotoxin remained among those hired =50 years before enrolment. In contrast, there was suggestion of an increased risk of lung cancer among those hired >50 years ago. Conclusions After examination of left truncation bias, an inverse dose-response between endotoxin and lung cancer remained for all subjects except those hired longest ago.


Checkoway H.,University of California at San Diego | Lundin J.I.,University of Washington | Costello S.,University of California at Berkeley | Ray R.,Fred Hutchinson Cancer Research Center | And 7 more authors.
British Journal of Cancer | Year: 2014

Background: Endotoxin (lipopolysaccharide) is a widespread contaminant in many environmental settings. Since the 1970s, there has been generally consistent evidence indicating reduced risks for lung cancer associated with occupational endotoxin exposure.Methods:We updated a case-cohort study nested within a cohort of 267 400 female textile workers in Shanghai, China. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. We applied Cox proportional hazards modelling to estimate exposure-response trends, adjusted for age and smoking, for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of ≤15 and >15 years since first exposure.Results:We observed no associations between cumulative exposure and lung cancer, irrespective of lag interval. In contrast, analyses by exposure time windows revealed modestly elevated, but not statistically significant relative risks (∼1.27) at the highest three exposure quintiles for exposures that occurred >15 years since first exposure.Conclusions:The findings do not support a protective effect of endotoxin, but are suggestive of possible lung cancer promotion with increasing time since first exposure. © 2014 Cancer Research UK. All rights reserved.


Checkoway H.,University of Washington | Ray R.M.,Fred Hutchinson Cancer Research Center | Lundin J.I.,University of Washington | Astrakianakis G.,University of British Columbia | And 10 more authors.
Occupational and Environmental Medicine | Year: 2011

Objectives: Numerous epidemiological studies of lung cancer among textile workers worldwide consistently indicate reduced risks related to cotton dust exposure, presumably due to endotoxin contamination. Our objective was to investigate associations with other exposures potentially related to lung cancer, including wool and synthetic fibre dusts, formaldehyde, silica, dyes and metals, that have only been studied to a limited extent in the textile industry. Methods: We conducted a case-cohort study nested within a cohort of 267 400 women textile workers in Shanghai, China. We compared work assignments and exposure histories of 628 incident lung cancer cases, diagnosed during 1989-1998, with those of a reference subcohort of 3188 workers. We reconstructed exposures with a job-exposure matrix developed specifically for textile factories. Cox proportional hazards modelling was applied to estimate age/smoking-adjusted relative risks (hazard ratios) and risk gradients associated with job assignments and specific agents other than cotton dust and endotoxin. Results: No associations were observed for lung cancer with wool, silk or synthetic fibre dusts, or with most other agents. However, increased risks, although statistically imprecise, were noted for ≥10 years' exposures to silica (adjusted HR 3.5, 95% CI 1.0 to 13) and ≥10 years' exposures to formaldehyde (adjusted HR 2.1, 95% CI 0.4 to 11). Conclusions: Exposures to silica and formaldehyde, although not widespread among the cohort, may have increased lung cancer risk. Silica is an established human lung carcinogen, whereas there is only weak prior evidence supporting an association with formaldehyde. Both exposures warrant consideration as potential lung carcinogens in textile manufacturing.


Gallagher L.G.,University of Washington | Davis L.B.,University of Washington | Ray R.M.,Fred Hutchinson Cancer Research Center | Psaty B.M.,University of Washington | And 5 more authors.
International Journal of Epidemiology | Year: 2011

Background: Few studies have examined the possible effects of reproductive factors on cardiovascular disease (CVD) risks in Asian women. Methods: A cohort of 267 400 female textile workers in Shanghai, China, was administered a questionnaire at enrolment (1989-91) and followed for mortality through 2000. Relative risks (hazard ratios) for ischaemic heart disease (IHD), ischaemic stroke and haemorrhagic stroke were calculated using Cox proportional hazards modelling, adjusting for relevant co-variates. Results: Risks were not consistently associated with age at menopause, parity, stillbirths, miscarriages or duration of lactation. An increasing trend in IHD mortality risk, but not stroke, was observed with decreasing age at menarche. There was no evidence of increased CVD mortality risk by oral or injectable contraceptive use or induced abortions. As expected, greater mortality rates from CVD and increased CVD risks were also observed with smoking. Conclusions: Use of steroid contraceptives, induced abortions and reduced parity from China's one-child-per-family policy has not had an adverse effect on risk of CVD mortality in this cohort. Published by Oxford University Press on behalf of the International Epidemiological Association. © The Author 2011; all rights reserved.


PubMed | University of Washington, Fred Hutchinson Cancer Research Center, University of British Columbia, Zhong Shan Hospital Cancer Center and 3 more.
Type: Journal Article | Journal: British journal of cancer | Year: 2014

Endotoxin (lipopolysaccharide) is a widespread contaminant in many environmental settings. Since the 1970s, there has been generally consistent evidence indicating reduced risks for lung cancer associated with occupational endotoxin exposure.We updated a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. We applied Cox proportional hazards modelling to estimate exposure-response trends, adjusted for age and smoking, for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of 15 and >15 years since first exposure.We observed no associations between cumulative exposure and lung cancer, irrespective of lag interval. In contrast, analyses by exposure time windows revealed modestly elevated, but not statistically significant relative risks (1.27) at the highest three exposure quintiles for exposures that occurred >15 years since first exposure.The findings do not support a protective effect of endotoxin, but are suggestive of possible lung cancer promotion with increasing time since first exposure.

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