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.

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.

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.

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.

North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin.

In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk.

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.

Augmentation mammaplasty and breast cancer: a 5-year update of the Los Angeles study.

We have previously reported on the risk of breast cancer in women during the first few years following cosmetic augmentation mammaplasty and are now presenting results after longer exposure. Long-term carcinogenicity of breast implants in humans has not been assessed previously. We conducted a retrospective cohort study of 3112 patients with a median of 10.6 years of postimplant experience (range 0.1 to 31.7 years). Patients were enrolled from surgeons' records, and cancer outcomes were monitored by the population-based cancer registry serving Los Angeles County. Because of confidentiality concerns, there was no direct patient contact. Twenty-one breast cancers were observed among the implant patients as compared with 31.7 expected, based on Los Angeles County incidence rates [standardized incidence ratio (SIR) = 66 percent, 95 percent confidence limits (CL): 41 percent, 101 percent]. For all other malignancies combined, 45 were observed and 50.0 were expected (SIR = 90 percent, CL: 66 percent, 120 percent). Although the numbers of cases were very small, increased frequencies of lung and vulvar cancers were observed. Based on the evidence to date, we conclude that there is no increase in breast cancer incidence following augmentation mammaplasty.

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.

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.

The relationship between breast cancer and augmentation mammaplasty: an epidemiologic study.

Surgical implantation of breast prostheses for cosmetic purposes has become increasingly popular, and by 1981, it was estimated that three-quarters of a million women had had such an operation. The long-term potential risks, particularly of breast cancer, of such procedures have not been properly investigated. To evaluate the potential breast cancer risk, we have conducted a retrospective cohort study of 3111 women followed through various public and medical records for a total of 18,476 person-years, with a median of 6.2 years per person. The cases of breast cancer were detected by means of a computerized match with the Los Angeles County Cancer Surveillance Program, a population-based cancer registry. Overall, 15.7 breast cancer cases were expected and 9 were observed, a nonsignificant deficit [standardized incidence ratio (SIR) = 57 percent, 95 percent confidence limits: 26 percent, 109 percent]. The cancers were generally diagnosed at an early stage. Among the 573 women aged 40 or older at implantation, 7.1 cases were expected and 8 were observed (SIR = 113 percent). In women whose implants were performed before the age of 40, only 1 case was observed whereas 8.6 cases were expected (SIR = 12 percent, 95 percent confidence limits: 0.3 percent, 65 percent), a significant difference. These data do not support an increased risk of breast cancer following augmentation mammaplasty. The low breast cancer rate in women having augmentation mammaplasty at a young age that many such women may have a reduced amount of breast tissue, but data on this are unavailable.

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.

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.

A case-control study of amyotrophic lateral sclerosis.

The authors conducted a study of 518 amyotrophic lateral sclerosis patients identified between 1977 and 1979 and 518 controls to investigate putative risk factors for this disease. Occupations at risk of electrical exposure were reported more often by patients (odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.4-13.0) as were electrical shocks producing unconsciousness (OR = 2.8, 95% CI = 1.0-9.9). Although an overall excess of physical trauma associated with unconsciousness was observed in the amyotrophic lateral sclerosis patients (OR = 1.6, 95% CI = 1.0-2.4), the effect was inversely associated with duration of the unconscious episodes, suggesting an effect of recall bias. Only slight differences were found for surgical traumata to the nervous system. Parkinsonism was reported more often among first degree relatives of cases (OR = 2.7, 95% CI = 1.1-7.6). The frequencies of prior poliomyelitis or other central nervous system diseases were similar for patients and controls. Occupational exposure to selected toxic substances was similar for patients and controls except for the manufacture of plastics (OR = 3.7, 95% CI = 1.0-20.5), although few details of these exposures were provided. No differences in occupations with exposure to animal skins or hides were observed.