Occupational trichloroethylene exposure and non-Hodgkin's lymphoma: a meta-analysis and review.

METHODS: Meta-analysis and review of 14 occupational cohort and four case-control studies of workers exposed to trichloroethylene (TCE) to investigate the relation between TCE exposure and the risk of non-Hodgkin's lymphoma (NHL). Studies were selected and categorised based on a priori criteria, and results from random effects meta-analyses are presented. RESULTS: The summary relative risk estimates (SRRE) for the group of cohort studies that had more detailed information on TCE exposure was 1.29 (95% CI 1.00 to 1.66) for the total cohort and 1.59 (95% CI 1.21 to 2.08) for the seven studies that identified a specific TCE exposed sub-cohort. SRREs for three studies with cumulative exposure information were 1.8 (95% CI 0.62 to 5.26) for the lowest exposure category and 1.41 (95% CI 0.61 to 3.23) for the highest category. Comparison of SRREs by levels of TCE exposure did not indicate exposure-response trends. The remaining cohort studies that identified TCE exposure but lacked detailed exposure information had an SRRE of 0.843 (95% CI 0.72 to 0.98). Case-control studies had an SRRE of 1.39 (95% CI 0.62 to 3.10). Statistically significant findings for the Group 1 studies were driven by the results from the subgroup of multiple industry cohort studies (conducted in Europe) (SRRE = 1.86; 95% CI 1.27 to 2.71). The SRRE for single industry cohort studies was not significantly elevated (SRRE = 1.25; 95% CI 0.87 to 1.79). CONCLUSIONS: Interpretation of overall findings is hampered by variability in results across the Group 1 studies, limited exposure assessments, lack of evidence of exposure response trends, lack of supportive information from toxicological and mechanistic data, and absence of consistent findings in epidemiologic studies of exposure and NHL. Although a modest positive association was found in the TCE sub-cohort analysis, a finding attributable to studies that included workers from multiple industries, there is insufficient evidence to suggest a causal link between TCE exposure and NHL.

Diabetes and endometrial cancer in the Iowa women's health study.

Diabetes has been associated with increased risk of endometrial cancer in some epidemiological studies. Body mass index (BMI) and other measures of obesity have been associated positively with both diabetes and endometrial cancer. It is not clear whether or not the association of diabetes with endometrial cancer is explained entirely by obesity. Thus, we sought to test the hypothesis that diabetes is not associated with endometrial cancer independent of obesity. We examined the association between self-reported diabetes (onset at >30 years of age) and incident endometrial cancer in a prospective cohort study of 24,664 postmenopausal women in Iowa. Over 12 years of follow-up, 346 cases occurred among the cohort at risk. Data were analyzed using proportional hazards regression models. Diabetes was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up. After adjustment for BMI, waist:hip ratio, and other covariates, the relative risk (RR) for women with diabetes versus women without diabetes was 1.43 [95% confidence interval (CI), 0.98-2.1]. The diabetes association was confined to women in the upper two BMI quintiles (RR, 1.47; 95% CI, 0.98-2.20), but a formal test of interaction was not statistically significant. Analyses that included diabetes ascertained at baseline and at follow-up gave similar results; the diabetes-associated RR in the higher BMI strata was 1.64 (95% CI, 1.16-2.31). We conclude that after adjustment for other risk factors, diabetes is associated with a modestly increased risk for endometrial cancer among women in this cohort.

Associations of general and abdominal obesity with multiple health outcomes in older women: the Iowa Women's Health Study.

BACKGROUND: Recent clinical guidelines on the health risks of obesity use body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) and waist circumference, but the waist-hip ratio may provide independent information. METHODS: To assess the joint and relative associations of BMI, waist circumference, and waist-hip ratio with multiple disease end points, we conducted a prospective cohort study of 31,702 Iowa women, aged 55 to 69 years and free of cancer, heart disease, and diabetes, assembled by random sampling and mail survey in 1986. Study end points were total and cause-specific mortality and incidence of site-specific cancers and self-reported diabetes, hypertension, and hip fracture over 11 to 12 years. RESULTS: The waist-hip ratio was the best anthropometric predictor of total mortality, with the multivariable-adjusted relative risk for quintile 5 vs 1 of 1.2 (95% confidence interval, 1.1-1.4), compared with 0.91 (95% confidence interval, 0.8-1.0) for BMI and 1.1 (95% confidence interval, 1.0-1. 3) for waist circumference. The waist-hip ratio was also associated positively with mortality from coronary heart disease, other cardiovascular diseases, cancer, and other causes. The waist-hip ratio was associated less consistently than BMI or waist circumference with cancer incidence. All anthropometric indexes were associated with incidence of diabetes and hypertension. For example, women simultaneously in the highest quintiles of BMI and waist-hip ratio had a relative risk of diabetes of 29 (95% confidence interval, 18-46) vs. women in the lowest combined quintiles. CONCLUSION: The waist-hip ratio offers additional prognostic information beyond BMI and waist circumference.

Physical activity and incidence of postmenopausal breast cancer.

Whether physical activity reduces the risk of postmenopausal breast cancer is uncertain; few studies have addressed this issue. We examined the association of leisure physical activity with breast cancer incidence among 37,105 postmenopausal participants in the Iowa Women's Health Study. Women reporting the highest level of physical activity at baseline compared with women with the lowest level of activity had an age-adjusted relative risk of breast cancer of 0.92 (95% confidence interval = 0.80-1.05). Women reporting any regular leisure-time physical activity had a relative risk of 0.97 (95% confidence interval = 0.87-1.08) compared with those reporting no such regular physical activity. Adjustment for potential confounders did not appreciably alter the findings. There is little evidence from this study that physical activity later in life is associated to any appreciable extent with breast cancer incidence.

Induced abortion and breast cancer risk.

Results from case-control studies suggest that induced abortion may be associated with a small increase in risk of breast cancer. While risk estimates from cohort studies have generally not observed such an association, these studies have had limited information regarding abortion and possible confounding variables. Therefore, we conducted a study among a cohort of post-menopausal women from whom detailed information regarding pregnancy outcomes as well as risk factors for breast cancer had been collected. The study sample included 37,247 Iowa Women's Health Study participants, 55-64 years of age at baseline in 1986, who reported no history of breast, or other, cancer (except non-melanoma skin cancer), and for whom information regarding pregnancy outcomes (that is, live birth, stillbirth, spontaneous abortion, ectopic pregnancy or induced abortion) was available. We used linkage with records of the State Health Registry of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, to estimate the incidence of breast cancer among cohort members through 1995. We calculated age-adjusted relative risks and 95% confidence intervals using Cox proportional hazards regression. Only 653 women (1.8%) reported an induced abortion. The age-adjusted relative risk of breast cancer among women with prior induced abortion compared with those without was 1.1 (95% CI = 0.8-1.6). Relative risks were higher among women whose age at first abortion was less than 20 or at least 30 years, for those whose abortion took place after their first birth or who never gave birth, and for those with early termination (0-2 months). These estimates varied from 1.3-1.7, but the confidence intervals around each were wide. Since most women in this cohort were beyond their reproductive years when abortion became legal in 1973, the low prevalence of induced abortion argues for a cautious interpretation.

Prospective study of diet and ovarian cancer.

Evidence on dietary risk factors for ovarian cancer is inconsistent, but some studies have suggested positive associations with dietary fat, lactose, and cholesterol and negative associations with green and yellow vegetable intake. By using information from the Iowa Women's Health Study, the authors investigated the association of epithelial ovarian cancer with dietary factors in a prospective study of 29,083 postmenopausal women. Dietary information was ascertained via a food frequency questionnaire mailed to participants in 1986. During 10 years of follow-up (1986-1995), 139 of the women developed incident epithelial ovarian cancer. Incidence of the disease was not associated with dietary fat intake. Lactose and cholesterol showed moderately elevated risks. Multivariable-adjusted relative risks for the lowest to highest quartiles of lactose intake were 1.00, 1.38, 1.25, and 1.60 (p for trend = 0.12). For cholesterol, the corresponding values were 1.00, 1.34, 1.86, and 1.55 (p for trend = 0.06). Consumption of eggs was also associated with an increased risk of ovarian cancer. Multivariable-adjusted relative risks for increasing frequency of egg consumption were 1.00 (<1/week), 1.12 (1/week), 2.04 (2-4/week), and 1.81 (>4/week) (p for trend = 0.04). Total vegetable intake was modestly and inversely associated with the risk of ovarian cancer (p for trend = 0.21). Green leafy vegetable intake was more strongly associated with a decreased risk: multivariable-adjusted relative risks for the lowest to highest intake levels were 1.00, 0.80, 0.87, and 0.44 (p = 0.01). These findings are generally in agreement with the results from previous, mostly case-control studies of diet and epithelial ovarian cancer.

Women's preferences for specialists who provide cancer screening and general medical care.

In order to determine what types of specialists women prefer for medical care, we examined responses from a cross-sectional survey of adult female patients in a health plan of the independent practice association model in the Minneapolis-St. Paul metropolitan area (n = 1,204). The response rate for the survey was 90%. The women expressing a preference (60% of responders) overwhelmingly preferred to see obstetrician-gynecologists for their breast examinations and Pap smears and strongly preferred family physicians or internists for the remainder of their cancer screening and general medical care. Thus, the majority of women expressed preferences for physicians of different specialties to provide their medical care.

The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer.

BACKGROUND: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. OBJECTIVE: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. DESIGN: Prospective cohort study. SETTING: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. PARTICIPANTS: Random sample of 41,837 female Iowa residents 55 to 69 years of age. MEASUREMENTS: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index. RESULTS: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10,000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10,000 person-years [CI, 69 to 92 deaths]). CONCLUSIONS: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.

Physical activity and mortality in postmenopausal women.

OBJECTIVE: To evaluate the association between physical activity and all case mortality in postmenopausal women. DESIGN: Prospective cohort study with 7 years of follow-up through December 31, 1992. SETTING AND PARTICIPANTS: Subjects were 40417 postmenopausal Iowa women, aged 55 to 69 years at baseline in 1986. Physical activity was assessed by mailed questionnaire. MAIN OUTCOME MEASURE: All-cause mortality (n=2260). RESULTS: After adjustment for potential confounders and excluding women who reported having cancer or heart disease and those who died in the first 3 years of follow-up, women who reported regular physical activity were at significantly reduced risk of death during follow-up compared with women who did not (relative risk [RR], 0.77; 95% confidence interval [CI], 0.66-0.90). Increasing frequency of moderate physical activity was associated with reduced risk of death during follow-up (from rarely or never engaging in activity to activity at least 4 times per week, RRs, 1.0 [referent], 0.76, 0.70, and 0.62; P value for trend<.001). A similar pattern was seen for vigorous physical activity (corresponding RRs, 1.0, 0.89, 0.74, and 0.57; Pvalue for trend=.06). Reduced risks of death with increased physical activity were evident for cardiovascular diseases (n=729) and respiratory illnesses (n=147). Women who engaged only in moderate but not vigorous physical activity also benefited, with moderate activity as infrequently as once per week demonstrating a reduced mortality risk of 0.78 (95% CI, 0.64-0.96). CONCLUSIONS: These results demonstrate a graded, inverse association between physical activity and all-cause mortality in postmenopausal women. These findings strengthen the confidence that population recommendations to engage in regular physical activity are applicable to postmenopausal women.

Weight variability and incident disease in older women: the Iowa Women's Health Study.

OBJECTIVE: To evaluate the association between weight variability and disease incidence in women. DESIGN: Prospective cohort study, following women from 1986 through 1992. METHODS: A population-based sample of 33834 women aged 55-69 y, free of cancer and heart disease, completed a mail-based survey that included self-reported body weights at ages 18, 30, 40, 50 y, and currently. Weight variability was defined as (1) the root mean square error around the slope of weight on age (RMSE); and (2) categorical measures of weight change. Outcome measures were incidence of myocardial infarction (MI); stroke; diabetes; breast, endometrial, lung, or other cancer; total and hip fractures. RESULTS: Adjusted relative risks of MI, stroke, diabetes, and hip fracture increased with increasing weight variability. The age and body mass index-adjusted relative risks (RR) for highest vs lowest quartile of RMSE were: MI: 2.03; stroke: 1.61; diabetes: 1.42; breast cancer: 0.85; endometrial cancer: 0.88; lung cancer: 1.70; other cancer: 0.93; total fractures: 1.15; hip fractures: 1.45. The strongest associations between weight change categories and disease were for diabetes (RR compared to small gain/stable weight: large cycle, 1.72; small cycle, 1.55; large gain, 1.80; weight loss, 1.91; other pattern, 1.55). Large weight cycles were associated with higher risk of MI (RR = 1.89) and stroke (RR = 1.71). CONCLUSIONS: These findings are consistent with previous studies and suggest that weight variability is associated with higher risk of developing chronic diseases.

Why do patients of female physicians have higher rates of breast and cervical cancer screening?

OBJECTIVE: Women are more likely to receive breast and cervical cancer screening if they see female physicians. We studied whether this is due to differences between male and female physicians, or to differences in their patients. SETTING: Large midwestern, independent practice association style of health plan. DESIGN: We surveyed male and female primary care physicians matched for age and specialty and a stratified random sample of three of each physician's women patients. Physicians reported on their practice setting, their attitudes and practices regarding prevention, and their comfort and skill with various examinations. Patients reported on their sociodemographic characteristics, their attitudes and practices regarding prevention, and their preferences for physician gender. Claims data were used to calculate mammography and Pap smear screening rates for the physicians. PARTICIPANTS: We studied 154 female and 190 male internists and family physicians and 794 of their patients. MEASUREMENTS AND MAIN RESULTS: We compared the responses of male and female physicians and their patients and used multivariable analysis to identify the patient and physician factors that accounted for the differences in screening rates between male and female physicians. Female physicians were more likely to ask new patients about components of prevention, to believe in the effectiveness of mammography, to feel more personal responsibility for ensuring that their patients received screening, and to report more comfort in performing Pap smears and breast examinations. Patients of female physicians were more educated and less likely to be married, but did not differ in other sociodemographic characteristics. They had similar attitudes and practices regarding prevention, except that patients of male physicians were more likely to smoke. Significantly more patients of female physicians preferred a female for some component of care. In multivariable analyses, practice organization, patient preference for a female physician, and prevention orientation of female physicians accounted for up to 40% of screening rate differences between female and male physicians for Pap smears, and 33% for mammography. CONCLUSIONS: Differences in beliefs of male and female physicians and patient preference for a female provider contribute independently to the higher rate of breast and cervical cancer screening by female physicians.

Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women.

BACKGROUND: The role of dietary antioxidant vitamins in preventing coronary heart disease has aroused considerable interest because of the knowledge that oxidative modification of low-density lipoprotein may promote atherosclerosis. METHODS: We studied 34,486 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E, and C from food sources and supplements. During approximately seven years of follow-up (ending December 31, 1992), 242 of the women died of coronary heart disease. RESULTS: In analyses adjusted for age and dietary energy intake, vitamin E consumption appeared to be inversely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21,809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42, and 0.42; P for trend 0.008). After adjustment for possible confounding variables, this inverse association remained (relative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32, and 0.38; P for trend, 0.004). There was little evidence that the intake of vitamin E from supplements was associated with a decreased risk of death from coronary heart disease, but the effects of high-dose supplementation and the duration of supplement use could not be definitely addressed. Intake of vitamins A and C did not appear to be associated with the risk of death form coronary heart disease. CONCLUSIONS: These results suggest that in postmenopausal women the intake of vitamin E from food is inversely associated with the risk of death from coronary heart disease and that such women can lower their risk without using vitamin supplements. By contrast, the intake of vitamins A and C was not associated with lower risks of dying from coronary disease.

Physical activity, waist-to-hip ratio, and other risk factors for ovarian cancer: a follow-up study of older women.

We investigated the association of epithelial ovarian cancer with physical activity, waist-to-hip ratio, reproductive factors, and family history of cancer in a prospective cohort study of 31,396 postmenopausal women. Ninety-seven women developed incident epithelial ovarian cancer over 7 years. The number of livebirths was associated with lower risk (multivariate-adjusted relative risks for 1-2, 3-4, and > 4 livebirths compared with nulliparity were 0.64, 0.47, and 0.43, respectively). A family history of ovarian cancer in a first-degree relative was associated with a 2.5 times greater risk (95% confidence interval = 0.90-6.7). Multivariate-adjusted relative risks for the upper three quartiles of waist-to-hip ratio compared with the lowest quartile were 2.0, 1.6, and 2.3, respectively. Women with "moderate" and "high" levels of physical activity compared with those with "low" physical activity had relative risks of 1.4 and 2.1, respectively. Positive associations of physical activity and waist-to-hip ratio with ovarian cancer seem inconsistent with existing theories of ovarian cancer pathogenesis.

Hormonal replacement therapy and morbidity and mortality in a prospective study of postmenopausal women.

We assessed the association of hormonal replacement therapy with mortality and incidence of multiple diseases in over 40,000 postmenopausal women followed for 6 years as part of the Iowa Women's Health Study. Compared with women who never used hormone replacement therapy, current users had multivariate adjusted relative risks (RR) as follows: total mortality (RR = 0.78; 95% confidence interval [CI] = 0.65, 0.94), coronary heart disease mortality (RR = 0.74; 95% CI = 0.48, 1.12), endometrial cancer incidence (RR = 4.3; 95% CI = 2.7, 6.9), breast cancer incidence (RR = 1.23; 95% CI = 0.99, 1.55), colon cancer incidence (RR = 0.72; 95% CI = 0.46, 1.12), and hip fracture incidence (RR = 0.53; 95% CI = 0.31, 0.91).