Plasma equol concentration is not associated with breast cancer and fibrocystic breast conditions among women in Shanghai, China.

Equol (a bacterial metabolite of the soy isoflavone daidzein) is produced by 30% to 50% of humans and may be associated with health outcomes. We hypothesized that plasma equol would be inversely associated with risks of fibrocystic breast conditions (FBC) and breast cancer (BC). Plasma from women in a breast self-examination trial in Shanghai with BC (n=269) or FBC (n=443), and age-matched controls (n=1027) was analyzed for isoflavones. Equol was grouped into categories (<20, 20-<45, and ≥45nmol/L) and, among women with daidzein ≥20nmol/L, the log10 equol:daidzein ratio was grouped into tertiles. Where available, non-cancerous tissue (NCT) adjacent to the carcinomas from women with BC were classified as non-proliferative or proliferative (n=130 and 172, respectively). The lesions from women with FBC were similarly classified (n=99 and 92, respectively). Odds ratios (OR) and 95% confidence intervals (CI) were calculated across equol categories and tertiles of log10 equol:daidzein ratio. Equol categories were not associated with FBC or BC (P>.05). For log10 equol:daidzein, compared to controls there were positive associations in the mid tertile for proliferative FBC (OR 2.06, 95% CI 1.08-3.93), BC with proliferative NCT (OR 2.95, 95% CI 1.37-6.35), and all BC regardless of histology (OR 2.37, 95% CI 1.43-3.95). However, trends in ORs with increasing plasma equol values or equol:daidzein ratios were not observed (P>.05). The results of this study do not provide evidence that equol plays a role in the etiology of these breast conditions. However, further work is needed to confirm or refute this conclusion.

Shift work and breast cancer among women textile workers in Shanghai, China.

PURPOSE: Although night-shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China. METHODS: The study included 1,709 incident breast cancer cases and 4,780 non-cases. Data on historical shift work schedules were collected by categorized jobs from the factories, where the study subjects had worked, and then were linked to the complete work histories of each subject. No jobs in the factories involved exclusively night-shift work. Therefore, night shift was evaluated as part of a rotating shift work pattern. Hazard ratios and 95 % confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design for years of night-shift work and the total number of nights worked. Additionally, analyses were repeated with exposures lagged by 10 and 20 years. RESULTS: We observed no associations with either years of night-shift work or number of nights worked during the entire employment period, irrespective of lag intervals. Findings from the age-stratified analyses were very similar to those observed for the entire study population. CONCLUSIONS: The findings from this study provide no evidence to support the hypothesis that shift work increases breast cancer risk. The positive association between shift work and breast cancer observed in Western populations, but not observed in this and other studies of the Chinese population, suggests that the effect of shift work on breast cancer risk may be different in Asian and Caucasian women.

Occupational exposure to magnetic fields and breast cancer among women textile workers in Shanghai, China.

Exposure to magnetic fields (MFs) is hypothesized to increase the risk of breast cancer by reducing production of melatonin by the pineal gland. A nested case-cohort study was conducted to investigate the association between occupational exposure to MFs and the risk of breast cancer within a cohort of 267,400 female textile workers in Shanghai, China. The study included 1,687 incident breast cancer cases diagnosed from 1989 to 2000 and 4,702 noncases selected from the cohort. Subjects' complete work histories were linked to a job-exposure matrix developed specifically for the present study to estimate cumulative MF exposure. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards modeling that was adapted for the case-cohort design. Hazard ratios were estimated in relation to cumulative exposure during a woman's entire working years. No association was observed between cumulative exposure to MFs and overall risk of breast cancer. The hazard ratio for the highest compared with the lowest quartile of cumulative exposure was 1.03 (95% confidence interval: 0.87, 1.21). Similar null findings were observed when exposures were lagged and stratified by age at breast cancer diagnosis. The findings do not support the hypothesis that MF exposure increases the risk of breast cancer.

Evidence of a paradoxical relationship between endotoxin and lung cancer after accounting for left truncation in a study of Chinese female textile workers.

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.

Occupational exposures and mortality from cardiovascular disease among women textile workers in Shanghai, China.

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.

Reproductive history and mortality from cardiovascular disease among women textile workers in Shanghai, China.

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.

Risk of lung cancer in relation to contiguous windows of endotoxin exposure among female textile workers in Shanghai.

OBJECTIVE: Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer. METHODS: Data were reanalyzed from a case-cohort study (602 cases, 3,038 subcohort) of female textile workers in Shanghai, China. Cumulative endotoxin exposure was partitioned into two windows: ≥20 and <20 years before risk. Exposure-response relations were examined using categorical and non-linear (semi-parametric) models, accounting for confounding by previous exposure windows. RESULTS: There was an inverse trend of decreasing risk of lung cancer associated with increasing levels of endotoxin exposure ≥20 years before risk (p trend = 0.02). Women in the highest two categories of cumulative exposures had hazard ratios of 0.78 (95% CI 0.60-1.03) and 0.77 (95% CI 0.58-1.02) for lung cancer, respectively, in comparison with unexposed textile workers. There was, however, a weaker association and not statistically significant between lung cancer and endotoxin exposure accumulated in the more recent window (<20 years before risk). CONCLUSION: Results provide further evidence that endotoxin exposure that occurred 20 years or more before risk confers the strongest protection against lung cancer, indicating a possible early anti-carcinogenic effect. Further studies are needed to better understand the underlying biological mechanisms for this effect.

Selected estrogen receptor 1 and androgen receptor gene polymorphisms in relation to risk of breast cancer and fibrocystic breast conditions among Chinese women.

BACKGROUND: Polymorphisms in sex hormone receptor-encoding genes may alter the activity of sex hormone receptors and thereby affect susceptibility to breast cancer and related outcomes. METHODS: In a case-control study of women from Shanghai, China, we examined the risk of breast cancer and fibrocystic breast conditions associated with the ESR1 PvuII (rs2234693) and XbaI (rs9340799) and AR CAG repeat ((CAG)(n)) and GGC repeat ((GGC)(n)) polymorphisms among 614 women with breast cancer, 467 women with fibrocystic conditions, and 879 women without breast disease. We also evaluated whether risk differed by the presence/absence of proliferative changes (in the extratumoral epithelium or fibrocystic lesion), menopausal status, or body mass index (BMI). Age-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using logistic regression. RESULTS: Only associations with AR (CAG)(n) and (GGC)(n) genotypes were detected. Allocating AR (CAG)(n) genotypes into six categories, with the (CAG)(22-24)/(CAG)(22-24) genotype category designated as the reference group, the (CAG)(>24)/(CAG)(>24) genotype category was associated with an increased risk of fibrocystic breast conditions (OR, 1.8; 95% CI, 1.1-3.0). Relative to the AR (GGC)(17)/(GGC)(17) genotype, the (GGC)(17)/(GGC)(14) genotype was associated with elevated risks of incident breast cancer (OR, 2.6; 95% CI, 1.3-5.4) and fibrocystic conditions (OR, 2.3; 95% CI, 1.1-4.5). Results did not differ according to proliferation status, menopausal status, or BMI. CONCLUSION: Although these data lend support for a link between AR variation and breast disease development, given the low frequency of the putative risk-conferring genotypes and other constraints, further confirmation of our results is needed.

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.

BACKGROUND: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. OBJECTIVES: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. DESIGN: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. RESULTS: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. CONCLUSION: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai, China.

CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted.

Occupational risk factors for endometrial cancer among textile workers in Shanghai, China.

OBJECTIVE: A case-cohort study was conducted to investigate associations between occupational exposures and endometrial cancer nested within a large cohort of textile workers in Shanghai, China. METHODS: The study included 176 incident endometrial cancer cases diagnosed from 1989 to 1998 and a randomly-selected age-stratified reference subcohort (n = 3,061). Study subjects' complete work histories were linked to a job-exposure matrix developed specifically for the textile industry to assess occupational exposures. Hazard ratios (HR) and 95% confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design, adjusting for age at menarche and a composite variable of gravidity and parity. RESULTS: An increased risk of endometrial cancer was detected among women who had worked for > or =10 years in silk production (HR = 3.8, 95% CI 1.2-11.8) and had exposure to silk dust (HR = 1.7, 95% CI 0.9-3.4). Albeit with few exposed women (two cases and eight subcohort women), there was a 7.4-fold increased risk associated with > or =10 years of silica dust exposure (95% CI 1.4-39.7). CONCLUSIONS: The findings suggest that some textile industry exposures might play a role in endometrial carcinoma and should be further replicated in other occupational settings.

Polymorphisms in steroid hormone biosynthesis genes and risk of breast cancer and fibrocystic breast conditions in Chinese women.

Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a case-control study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA)n] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1, and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women.

Occupational exposures and ovarian cancer in textile workers.

BACKGROUND: Occupational risk factors for ovarian cancer have been investigated only to a limited extent. We conducted a case-cohort study to examine associations between occupational exposures and ovarian cancer in the textile industry. METHODS: We compared 261 incident ovarian cancer cases diagnosed between 1989 and 1998 with an age-stratified reference subcohort (n = 3199) from a cohort of 267,400 textile workers in Shanghai, China. Occupational exposures were assessed by job-exposure matrices designed for the textile industry, and estimates of quantitative cotton dust and endotoxin. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox proportional hazards modeling adapted for the case-cohort design. RESULTS: A decreased risk of ovarian cancer was associated with ever having worked in cotton manufacturing production (HR = 0.7; 95% CI = 0.4-1.0). An increased risk was associated with ever having worked in textile finishing (2.1; 0.9-5.0). We found an increasing risk of ovarian cancer associated with cumulative exposure to silica dust (for <10 years exposure, HR = 6.8 [CI = 0.6-76]; for > or =10 years, 5.6 [1.3-23.6]), although these results are based on only 8 exposed subcohort women (0.3%) and 4 cases (1.3%). We also detected inverse risk gradients for cumulative exposures to endotoxin when exposures were lagged by 20 years (in highest quartile, HR = 0.6 [CI = 0.4-1.1]). CONCLUSION: Silica dust may increase the risk of ovarian cancer, and cotton dust and endotoxin may reduce risk.

Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women.

Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n=615) or fibrocystic breast conditions (n=467) were compared to women without clinical breast disease (n=878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105-Val allele (OR=1.33, 95% CI, 0.99-1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who had breast cancer with extra-tumoral tissue proliferation (OR=1.77, 95% CI, 1.03-3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105-Val allele needs confirmation in other studies.

Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China.

BACKGROUND: Proliferative benign breast conditions are associated with elevated risk of breast cancer, whereas nonproliferative conditions are not strongly associated with risk. Factors acting before onset of hyperplasia might be associated with both benign conditions and breast cancer, whereas those on the proliferative disease-to-cancer pathway would be associated only with cancer. Soy isoflavone exposure may influence breast cancer risk, but little is known of its association with benign conditions. MATERIALS AND METHODS: We examined possible relationships between plasma genistein and daidzein concentrations and risk of breast disease in women, in a breast self-examination trial in Shanghai, China, diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304), and 1,002 age-matched controls with no known breast disease. Benign conditions were classified as nonproliferative (n = 131) or proliferative with or without atypia (n = 173). RESULTS: Isoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer, both with and without concomitant proliferative changes in ipsilateral noncancerous mammary epithelium (P(trend) < 0.01 for all comparisons with controls). Women in the highest quartile of plasma genistein (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95% confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95% confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42 ng/mL). Observed risks for breast cancer with and without surrounding proliferative changes were not different, respectively, from observed risks for benign proliferative and nonproliferative conditions alone. CONCLUSION: Isoflavone exposure was inversely associated with fibrocystic breast conditions and breast cancer, and the results suggest that effects on cancer risk occur early in carcinogenesis.

Erythrocyte fatty acids and breast cancer risk: a case-control study in Shanghai, China.

BACKGROUND: The role of individual fatty acids in the development and progression of breast cancer is unclear. Although in vitro and animal experiments have supported an inverse association between intake of long chain n-3 fatty acids [primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid] and breast cancer risk, findings from population studies are inconsistent. Recent studies have also shown associations between the ratio of saturated to monounsaturated fatty acids (SI) and breast cancer risk. The SI reflects the activity of several genes involved in lipid metabolism, including fatty acid synthase and steroyl coenzyme-A desaturase, that have been shown to be overexpressed in breast cancer. OBJECTIVE: The purpose of this analysis was to determine the association between erythrocyte fatty acid concentrations and breast cancer risk among women participating in a randomized trial of breast self-examination in Shanghai, China. DESIGN: We conducted a case-control study. Erythrocyte fatty acid concentrations were determined in specimens from 322 women with histologically confirmed breast cancer and 1030 frequency age-matched control women. RESULTS: We report a significant direct association among palmitic, gamma-linolenic, palmitoleic, and vaccenic acids and risk of breast cancer. Total n-3 fatty acids, EPA, and the SI for palmitic to palmitoleic acid were associated with significantly lower risk of breast cancer. CONCLUSION: Our results support a protective effect of n-3 fatty acids on breast cancer risk and provide additional evidence for the importance of evaluating the ratio of fatty acids when evaluating diet and breast cancer risk.

Occupational exposures and breast cancer among women textile workers in Shanghai.

BACKGROUND: Breast cancer incidence rates have been increasing in China over the past 2 decades. Most studies have focused on reproductive, dietary, and genetic risk factors. Little is known about the contribution of occupational exposures. METHODS: We conducted a case-cohort study within a cohort of female textile workers who had participated in a randomized trial of breast self-examination in Shanghai, China. We compared 1709 incident breast cancer cases with an age-stratified reference subcohort (n = 3155 noncases). Cox proportional hazards modeling, adapted for the case-cohort design, was used to estimate hazard ratios for breast cancer in relation to duration of employment in various job processes and duration of exposure to several agents. We also evaluated the associations of cotton dust and endotoxin with breast cancer. RESULTS: Cumulative exposures to cotton dust and endotoxin demonstrated strong inverse gradients with breast cancer risk when exposures were lagged by 20 years (trend P-values <0.001). We did not observe consistent associations with exposures to electromagnetic fields, solvents, or other chemicals. CONCLUSION: Endotoxin or other components of cotton dust exposures may have reduced risks for breast cancer in this cohort, perhaps acting at early stages of carcinogenesis. Replication of these findings in other occupational settings with similar exposures will be needed to confirm or refute any hypothesis regarding protection against breast cancer.

Lung cancer risk among female textile workers exposed to endotoxin.

BACKGROUND: Reduced risk of lung cancer among workers in the cotton textile industry has been observed since the 1970s. Bacterial endotoxin, a contaminant of raw cotton fiber and cotton dust, has been proposed as a protective agent that may act through the innate and acquired immune systems. We examine the association between endotoxin exposure and lung cancer risk in a cohort of female textile workers. METHODS: We conducted a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared the cumulative exposure histories of 628 case patients diagnosed with incident lung cancer from January 1, 1989, through December 31, 1998, with those of a lung cancer-free reference subcohort of 3184 workers who were frequency matched by 5-year age-groups to all cancer patients in the cohort. Cumulative endotoxin exposure for all participants was based on historic measurements and on additional measurements for this study. Relative risks and 95% confidence intervals (CIs) were estimated by hazard ratios (HRs) from Cox proportional hazards models. We conducted exposure-response trend analyses by use of cumulative exposures with lag times of 0, 5, 10, 15, or 20 years to account for disease latency. All analyses controlled for age and smoking status. All statistical tests were two-sided. RESULTS: Cumulative exposure to endotoxin was strongly, statistically significantly, and inversely associated with lung cancer risk. The inverse trend was greatest with a 20-year lag time, for which highest endotoxin exposure was associated with a statistically significantly 40% less risk of lung cancer (HR = 0.60, 95% CI = 0.43 to 0.83; P(trend) across quintiles = .002) than non-exposure. From a reported population rate of lung cancer among women in Shanghai of 19.1 per 100,000 for the year 2000 and the estimated reduction in risk of lung cancer observed for 20 years of endotoxin exposure in this population of workers, the incidence of lung cancer in this cohort was reduced by approximately 7.6 per 100,000 (range = 3.2-10.9 per 100,000). CONCLUSIONS: Long-term and high-level exposure to endotoxin, compared with no exposure, appears to be associated with a reduced risk of lung cancer in this cohort.

Menstrual and reproductive factors in relation to risk of endometrial cancer in Chinese women.

Menstrual, reproductive and contraceptive factors have been associated with risk of endometrial cancer in populations where the incidence of this tumor is high. To investigate associations between these factors in a low-risk population with a low prevalence of hormone replacement therapy, we conducted a cohort study among 267,400 women employed in the textile industry in Shanghai, China. Menstrual, reproductive and other factors were ascertained at baseline in 1989-1991, and women were followed for incident endometrial cancer through 31 December 1998 (n = 206). Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Risk of endometrial cancer decreased with increasing age at menarche (p-trend = 0.004). Among menopausal women, risk increased with age at menopause and increasing years of menstruation. Compared to women with one live birth, risk was increased in relation to nulliparity (Hazard ratio = 3.95, 95% CI 1.43-10.86). Risk was decreased with increasing age at first live birth (p-trend = 0.03). There was a decreased risk associated with ever use of an intrauterine device (HR = 0.56, 95% CI 0.35-0.88) and use of oral contraceptives for > or =2 years (HR = 0.50, 95% CI 0.23-1.07). This prospective study confirms findings from previous case-control studies relating menstrual, reproductive, and contraceptive factors and endometrial carcinoma.