Passive smoking and Parkinson's disease in California Teachers.

INTRODUCTION: Tobacco smoking is consistently inversely associated with Parkinson's disease (PD) in men and women; recently this has been related to reverse causation, prompting questions as to whether similar patterns exist for passive smoke exposure. We used baseline and follow-up data from the California Teachers Study, a prospective cohort of women, to investigate whether timing, location and cumulative measures of intensity and duration of passive smoke exposure are associated with PD risk. METHODS: Using a nested case-control approach, we included 224 diagnostically validated cases (158 with no history of personal smoking) and selected 3230 age- and race-matched controls (1973 with no history of personal smoking). We estimated odds ratios(ORs) and 95% confidence intervals(CI) by fitting adjusted multivariable unconditional logistic regression models. RESULTS: Among lifelong non-smokers, passive smoke exposure combined across all settings and accumulated over a lifetime was not associated with PD risk (OR = 1.18, 95% CI 0.60, 2.30). Workplace exposure was also not associated with risk. Household exposure during adulthood but not childhood was inversely associated with PD (OR = 0.59, 95% CI 0.40, 0.87). Exposure to passive smoke in other social settings was positively associated with PD (OR = 1.62, 95% CI 1.11, 2.36). These contradictory results may be attributable to chance due to multiple comparisons in subgroup analyses. No pattern emerged to suggest that increasing years of passive smoke exposure, smokiness of the setting, or combined smokiness by exposure years was associated with lower PD risk. CONCLUSION: Results do not convincingly support a protective effect of passive smoking in PD.

Lifetime exposure to estrogens and Parkinson's disease in California teachers.

INTRODUCTION: Parkinson's disease (PD) is consistently observed to occur less frequently in women than men, prompting investigation into whether estrogen protects against neurodegeneration of dopaminergic neurons. METHODS: We used baseline data in the California Teachers Study, a prospective cohort of women, to investigate whether reproductive factors indicating higher long-term estrogen levels are associated with PD using a nested case-control approach. We identified 228 PD cases and 3349 unaffected controls frequency matched by age and race. RESULTS: Women who reported using combined estrogen/progesterone therapy or progesterone only formulations had a 57% increase in PD risk (OR = 1.57, 95% CI = 1.06, 2.34) compared to never having used HT. Compared to women with menopause at 50-52 years, menopause at younger (<35-46 years: OR = 0.59, 95% CI = 0.37, 0.94) and older ages (≥53 years: OR = 0.54, 95% CI = 0.36, 0.83) had lower PD risk. A derived composite estrogen summary score for women's exposure to both endogenous and exogenous estrogens throughout life indicated that women with presumed higher cumulative lifetime levels of estrogen (a score of 3-5) had a significantly reduced PD risk [(OR = 0.57, 95% CI = 0.35, 0.91) relative to those with lower lifetime estrogen exposure or a composite estrogen summary score of 0-1]. CONCLUSIONS: These results provide some support for the hypothesis that lifelong high estrogen is protective in PD, suggesting that the level and persistence of exposure over the long term may be important in PD risk reduction.

Long-term and baseline recreational physical activity and risk of endometrial cancer: the California Teachers Study.

BACKGROUND: Physical activity may be associated with decreasing endometrial cancer risk; it remains unclear whether the association is modified by body size. METHODS: Among 93 888 eligible California Teachers Study participants, 976 were diagnosed with incident endometrial cancer between 1995-1996 and 2007. Cox proportional hazards regression methods were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with long-term (high school through age 54 years) and baseline (3 years prior to joining the cohort) strenuous and moderate recreational physical activity, overall and by body size. RESULTS: Increased baseline strenuous recreational physical activity was associated with decreased endometrial cancer risk (Ptrend=0.006) with approximately 25% lower risk among women exercising >3 h per week per year than among those exercising <1/2 h per week per year (RR, 0.76; 95% CI, 0.63-0.92). This inverse association was observed among overweight/obese women (body mass index ≥25 kg m(-2); Ptrend=0.006), but not among thinner women (Ptrend=0.12). Baseline moderate activity was associated with lower risk among overweight/obese women. CONCLUSION: Increasing physical activity, particularly strenuous activity, may be a lifestyle change that overweight and obese women can implement to reduce their endometrial cancer risk.

Family history of haematopoietic malignancies and non-Hodgkin's lymphoma risk in the California Teachers Study.

Family history of haematopoietic malignancies appears to be a risk factor for non-Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is unclear. Among 121 216 women participating in the prospective California Teachers Study, NHL risk varied by type of haematopoietic malignancy and gender of the relative.

Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology.

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case-control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.

Correlates of vitamin supplement use in the United States: data from the California Teachers Study cohort.

OBJECTIVE: To describe factors associated with vitamin supplement use in a large cohort of adult women. METHODS: California teachers and administrators (n = 133,479) completed a questionnaire on lifestyle factors and medical history. Specific supplement users regularly used at least one specific vitamin supplement in the past year; multivitamin users regularly used a multivitamin; and multivitamin and specific supplement users took a multivitamin and one or more specific supplements. Associations between supplement use and other variables were quantified using means, cross-tabulations, and age-adjusted prevalence odds ratios. RESULTS: Multivitamin and specific supplement users tended to be older and Caucasian. Compared to non-users, they were also leaner (odds ratio [OR] for BMI > or = 30 kg/m2 = 0.6 for specific supplement users with or without multivitamins, and OR = 0.7 for multivitamin only users), and were less likely to be current smokers (OR for current smoking = 0.8 for multivitamin plus specific supplement users, OR = 0.9 for specific supplement only users, and OR = 0.7 for multivitamin only users). Specific supplement users (with or without multivitamins) were more likely to use cancer screening tests, eat fruits and vegetables, and exercise than were multivitamin only users or non-users. CONCLUSIONS: A variety of demographic, dietary, and health-related factors were associated with different categories of supplement use.

Changing relationship between socioeconomic status and prostate cancer incidence.

BACKGROUND: Understanding the relationship between socioeconomic status (SES) and prostate cancer incidence could identify populations that should be targeted for intervention and prevention programs. We examined this relationship within the major racial/ethnic groups during the period 1972 through 1997, which spans the introduction of prostate-specific antigen (PSA) testing. METHODS: We used data from the population-based Los Angeles Cancer Surveillance Program to examine age-adjusted prostate cancer incidence rates in five SES groups over three specific calendar periods by racial/ethnic subpopulation (white, black, Asian, and Hispanic) and by stage of disease at diagnosis. Linear regression analysis was used to test for trends in the age-adjusted incidence rates that were associated with increasing levels of SES. All P values were two-sided. RESULTS: For men diagnosed with prostate cancer before 1987, when the test for PSA was not widely available, we found no association between SES and the incidence of prostate cancer in any of four racial/ethnic subpopulations or between SES and the stage of disease at diagnosis. In contrast, among men who were diagnosed with prostate cancer after 1987, SES was statistically significantly and positively associated with prostate cancer incidence in men from all racial/ethnic subpopulations except Asians (P =.01 for white men, P =.001 for black men, P =.02 for Hispanic men, P =.06 for Asian men, and P =.01 for all men combined). Higher SES was statistically significantly associated with cancers of earlier stage (P =.01 for localized cancer and P =.00 for regional cancer) for men who were diagnosed with prostate cancer after 1987. CONCLUSIONS: The association between SES and prostate cancer incidence after 1987 may reflect more prevalent PSA screening in populations with higher SES due to their greater access to health care. SES should, therefore, be considered an important factor in interpreting variations and time trends in prostate cancer incidence.

Representativeness of a roster of volunteer North American twins with chronic disease.

To identify large numbers of twins affected by chronic disease as potential subjects for studies of environmental and genetic chronic disease determinants, we advertised for affected twins over the period 1980-91 in newspapers across North America. Responses were received from 17 245 twin pairs in which cases of cancer or other chronic disease had occurred. To assess the representativeness of affected twins identified by advertising, we evaluated the pattern of reporting, compared the cases identified to the number of cases estimated to be prevalent among all North American twins, compared the cases to population-based singleton case series, compared the healthy co-twins to population-based samples of healthy persons, assessed the impact on ascertainment of opinions about disease causation, compared the pattern of prospective to retrospective ascertainment of disease in the originally unaffected co-twins of cases, and compared the results of the prospective ascertainment of disease in co-twins to comparable published estimates. Youth, gender, zygosity, education, and disease concordance were found to be overall determinants of ascertainment. Disease-discordant DZ twins appeared to be modestly underascertained. While somewhat better educated, both concordant and discordant pairs were judged to be reasonably representative of affected non-Hispanic white North American twin pairs of comparable status, ie of comparable age, sex, race, and zygosity. If interpreted with caution, the concordance patterns of such twins can be used to generate genetic hypotheses, but should not be the basis of definitive heritability analyses. We conclude that advertising offers a method of identifying pairs of twins that can serve as subjects for studies designed to identify disease determinants.

Breast cancer stage at diagnosis and survival among patients with prior breast implants.

Longstanding concern exists regarding the potential for women with breast implants to experience delayed detection of breast cancer. Furthermore, survival among cosmetic breast implant patients who subsequently develop breast cancer is a concern. Since 1976, this institution has monitored cancer incidence in a cohort of 3182 women who underwent cosmetic breast augmentation between 1959 and 1981. The distributions of stage at diagnosis and survival of the 37 women who subsequently developed in situ or invasive breast cancer were compared with the observed population distributions. The distribution of stage at diagnosis for cosmetic breast implant patients who subsequently developed breast cancer was virtually identical to that of all breast cancer patients in Los Angeles County who were of the same age and race, and were diagnosed during the same time period. Furthermore, the 5-year survival rate of the 37 patients did not differ from that which would be expected based on rates established by the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. These results suggest that cosmetic breast implant patients are not at increased risk of delayed detection of breast cancer, nor do they suffer a poorer prognosis when breast cancer does occur. Although the number of breast cancer patients in this study is small, the results are highly consistent with the existing epidemiologic evidence related to breast cancer detection and survival among breast implant patients. Although breast implant patients should continue appropriate breast cancer screening behavior, there seems to be no cause for alarm.

Tamoxifen therapy for breast cancer and endometrial cancer risk.

BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.

Impaired cytotoxic T lymphocyte activity in systemic lupus erythematosus following in vitro polyclonal T cell stimulation: a contributory role for non-T cells.

To determine whether non-T cells contribute to impaired generation of nonrestricted cytotoxic T lymphocyte (CTL) activity in human SLE, peripheral blood mononuclear cells (PBMC) and sort-purified T cells from normal subjects and SLE patients were stimulated with anti-CD3 mAb, maintained in IL2, and assayed for cytolytic activity against 51Cr-labeled Daudi target cells. In addition, T cell and non-T cell fractions were isolated from nine pairs of monozygotic (MZ) twins discordant for SLE, reconstituted in a criss-cross pattern, and stimulated and assayed for cytolytic activity. Cytolytic responses were significantly lower in SLE PBMC cultures than in normal PBMC cultures. Addition of SLE serum to normal PBMC cultures did not inhibit generation of normal cytolytic responses, and neither 'resting' SLE PBMC prior to stimulation nor addition of neutralizing anti-IL10 mAb or costimulating anti-CD28 mAb restored generation of SLE cytolytic responses to normal. Nevertheless, despite the significantly greater cytolytic responses in normal PBMC cultures than in SLE PBMC cultures, cytolytic responses in normal purified T cell cultures were only modestly and insignificantly greater than those in SLE purified T cell cultures. Moreover, substitution of 'healthy' non-T cells for SLE non-T cells in four of the nine MZ twin-pairs appreciably enhanced cytolytic responses, and substitution of SLE non-T cells for 'healthy' non-T cells in five of the seven twin-pairs tested appreciably diminished cytolytic responses. Taken together, these results indicate that, in addition to any inherent SLE T cell abnormalities, impaired function of SLE non-T cells contributes to impaired generation of nonrestricted CTL activity.

Socioeconomic status and cancers of the female breast and reproductive organs: a comparison across racial/ethnic populations in Los Angeles County, California (United States).

OBJECTIVES: Despite the fact that socioeconomic status (SES) has been shown to have important implications in health related issues, population-based cancer registries in the United States do not routinely collect SES information. This study presents a model to estimate the SES of cancer patients in the registry database. METHODS: At the Los Angeles Cancer Surveillance Program (CSP), we developed a model to estimate each cancer patient's SES from aggregate measurements of the census tract of residence (n = 1,640) at time of diagnosis. We then applied the SES estimates to observe the relationship between SES and risk of cancers of the female breast and reproductive organs including cancers of the ovary, cervix uteri, and corpus uteri. The analyses were performed on the cumulative records (n = 127,819) of cancer patients diagnosed between 1972 and 1992 in Los Angeles County, California, for the mutually exclusive racial/ethnic groups of non-Hispanic Whites, Hispanic Whites, Blacks, Asians, and persons of other ethnic groups. RESULTS: We found SES is positively associated with female breast cancer, ovarian cancer, and cancer of the corpus uteri, but inversely associated with cervical cancer. These SES trends were quite consistent across age groups among non-Hispanic White women. Variations by race/ethnicity in the SES patterns were also found, with Asians exhibiting little association. CONCLUSIONS: Our model of measuring SES is sufficiently sensitive to capture the trends. Adopting the aggregate approach to measure SES in population-based registry data appears to be useful.

Are breast implants anticarcinogenic? A 14-year follow-up of the Los Angeles Study.

Despite decades of use, the long-term safety of breast implants in women remains a concern. While the incidence of breast cancer among women has increased dramatically in the past decade, the implant-related risk of carcinoma of the breast only recently has received widespread attention. An additional concern is that the presence of the implant may delay tumor detection. This study allows examination of breast cancer risk and detection issues among patients with long-term exposure. We conducted a record linkage cohort study of cosmetic breast implant patients. We abstracted the records of the private practices of 35 broad-certified plastic surgeons in Los Angeles County, California. We included 3182 white women who received cosmetic breast implants between 1953 and 1980. Spanish-surnamed women, nonresidents of Los Angeles County, and patients with prior subcutaneous mastectomy or breast cancer were excluded. Cancer outcomes through 1991 have been ascertained through record linkage with the Los Angeles County Cancer Surveillance Program. With a median follow-up of 14.4 years, 31 breast cancer cases were observed, compared with 49.2 expected, based on Los Angeles County population-based incidence rates (standardized incidence ratio = 63.0 percent; 95 percent confidence limits: 42.8 and 89.5 percent). The distribution of stage of disease at diagnosis among women with implants did not differ from that of all similar breast cancer patients in Los Angeles County. In Los Angeles County, augmentation mammaplasty patients experience a significantly lower than expected risk of breast cancer and no delay in breast cancer detection after an average of 14.4 years of exposure. While the linkage methodology allows the possibility of failing to detect diagnosed cancer cases and does not permit collection of some pertinent risk factors, the six other published epidemiologic studies on the topic also report breast cancer risk to be at or below the expected rate.

Impaired recovery and cytolytic function of CD56+ T and non-T cells in systemic lupus erythematosus following in vitro polyclonal T cell stimulation. Studies in unselected patients and monozygotic disease-discordant twins.

OBJECTIVE: To determine whether there is impaired generation and cytolytic function of CD56+ T cells and non-T cells in human systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 73 patients with SLE, 39 normal controls, and 9 pairs of monozygotic (MZ) twins discordant for SLE. PBMC were stimulated with anti-CD3 monoclonal antibody, maintained in interleukin-2, and assayed for percentages of total CD56+ cells and CD56+ T cells by flow cytometry, and for cytolytic activity against 51Cr-labeled Daudi target cells. RESULTS: Despite normal total cell expansion, the percentages of recovered CD56+ T cells and total CD56+ cells were 1.6-fold and 1.8-fold lower, respectively, in patients with SLE compared with normal controls (P = 0.011 and P < 0.001, respectively). Cytolytic activities of isolated total CD56+ cells and CD56+ T cells and were also reduced in patients with SLE compared with normal controls (P = 0.033). These defects associated with SLE were independent of disease activity and immunosuppressive medications, and they reflected impaired maturation of cytolytic effector cells rather than a deficiency in precursor cell number. In MZ twins discordant for SLE, recovered percentages of CD56+ cells and cytolytic responses were very low in 4 of 8 and 6 of 9 co-twins with SLE, respectively. Cellmixing experiments with the PBMC of the MZ twins demonstrated that the E+ cell fractions (containing all T cells and CD56+ non-T cells) from the co-twins with SLE had decreased ability to generate cytolytic activity compared with the corresponding E+ cell fractions from the healthy co-twins. However, recovered percentages of CD56+ cells and non-T cells and cytolytic responses were also depressed in 4 of 8 and 4 of 9 healthy co-twins, respectively. CONCLUSION: Impaired CD56+ T cell and non-T cell responses are a feature of SLE and may antedate the onset of clinical disease.

Impact of a mailed intervention on annual mammography and physician breast examinations among women at high risk of breast cancer.

Only a few studies have examined repeat annual mammography rates, and most studies find that such regularity is low, ranging from < 5% in the general population to between 14 and 20% of first-degree relatives. The present study tested the effectiveness of a mailed intervention designed to improve compliance with breast cancer screening guidelines among women at elevated familial risk. The study used a pretest-posttest control group design; 369 twin sisters of breast cancer cases were assigned alternately to an intervention or a control group on the basis of sequential registration numbers. The intervention consisted of written materials, an audiotape, and mailed reminders. The posttest was mailed 2.5 years after the intervention in order to provide adequate time to assess the regularity of screening. The intervention and control groups were virtually identical with respect to demographic and baseline screening characteristics. Of those who returned the follow-up questionnaire, annual physician breast examinations were 12.8% higher and annual mammograms were 10.3% higher in the intervention group than in the control group. The probability of annual screening with physician breast examination and mammography was higher in the intervention group, and the probability of annual mammography continued to be higher for women over age 52 years after controlling for baseline screening, year of diagnosis, education, and status of the twin. This result is consistent with improvements found in other studies. Women who did not return follow-up questionnaires were more likely to have had fewer physician breast examinations and mammograms and more likely to be in the intervention group than those who stayed in the study. Additionally, those who dropped out of the intervention arm perceived themselves to be less susceptible and perceived screening to be less effective than did those who dropped out of the control arm. Although the intervention caused many women to be screened more regularly, those who had not been screened in the past and those who held opinions that were not conducive to screening were more likely to drop out. This mailed intervention for high-risk women increased their rate of screening. Characteristics of women resistant to such programs have been identified; alternative strategies need to be developed to reach this small percentage of high-risk women who ignore their elevated susceptibility.

Adherence to screening examinations for colorectal cancer after diagnosis in a first-degree relative.

Reports of colorectal cancer screening behavior were collected from 83 twin sisters of colorectal cancer cases and compared to the patterns found by national surveys. Prior to the diagnosis of colorectal cancer in a twin, the unaffected cotwins were being screened at rates close to those of the general population. In the years after diagnosis the annual frequency of each exam increased by approximately 15 to 20 percentage points. By the time of response nearly 89% of these cotwins had at least one fecal occult blood test, 90% had at least one digital rectal exam, and 69% had a sigmoidoscopy in comparison to 44, 63, and 27% of the general population, respectively. However, despite the evident familial risk, within the year prior to the report, 42.3% of colorectal cancer twins had had a fecal occult blood test, 44.3% had had a digital rectal exam, and 16% had had a sigmoidoscopy exam (the comparable figures from the general population sample are 14.5, 19.3, and 4%, respectively). The colorectal cotwins have a higher rate of sigmoidoscopy screening than either the National Health Interview Survey or the breast cotwins. Both colorectal and breast cancer cotwins have a higher rate of fecal occult blood test and digital rectal exam than the NHIS sample. This suggests that those at increased risk of cancer in general, are more likely to obtain routine screening including fecal occult blood test and digital rectal exam as part of the physical exam; however, the specialized sigmoidoscopy screening is more likely to be provided to those at most risk.