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Targeting the first-degree relatives of people with a particular complex disease can offer a powerful approach to building a risk-based cohort for prospective studies of etiologic factors. Such a cohort provides both a sizable increase in the rate of accrual of newly incident cases, enriching for risk factors that are known or even unknown, and a high level of motivation among participants. A nationwide study of breast cancer in the United States and Puerto Rico, the Sister Study, made up of women who are each the sister of a woman with breast cancer, exemplifies this approach. In this paper, the authors provide power calculations to aid in the design of such studies and quantify their benefits for detecting both genetic variants related to risk and interactive effects of genetic and environmental factors. While the risk-based cohort can have markedly increased prevalences of rare causative alleles, most of the power advantages for this design is due to the increased rate of accrual of newly incident cases rather than the increase in any one individual allele. [ABSTRACT FROM AUTHOR]

Farm children face unique health risks due to sharing their residential environment with hazardous machinery and materials. Causes of mortality among farm children have not been comprehensively described. Objective: In the Agricultural Health Study (AHS) cohort, we examined causes of mortality among 21,360 children in Iowa and North Carolina between 1975 and 1998. Methods: We matched identifying information for children provided by mothers on self-administered questionnaires to state death registries (1975-1998). Data on farm and family characteristics were provided by parents via enrollment questionnaires (1993-1997). Standardized mortality ratios (SMRs) were calculated, using state mortality data to generate expected deaths. We used logistic regression to examine parent, child and farm characteristics associated with injury mortality. Results: There were 162 deaths in Iowa (SMR = 0.69; 95% confidence interval (CI) = 0.60, 0.81) and 26 deaths in North Carolina (SMR = 0.42; 95%CI = 0.28, 0.61) in children aged 0-19 years. This deficit was largely due to deaths in the first year of life. Although deaths from overall unintentional injury were not increased, excess agricultural machinery mortality was observed in Iowa (SMR = 9.25; 95% CI = 5.12, 16.70). In case-control comparisons, maternal age less than 25 years at child's birth (OR = 2.17; 95%CI = 1.05, 4.49) and having more than 2 children in the family (OR = 2.79; 95%CI = 1.47, 5.30) were associated with increased child injury mortality. For children under 14 years, participation in farm work was associated with increased risk of agricultural machine-related mortality (OR = 3.92; 95% CI = 1.04, 14.78). Conclusions: Parent and child characteristics associated with child injury mortality could be used to target farm safety interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Uranium miners are chronically exposed to low levels of radon and its progeny. We investigated whether radon exposure is associated with increased incidence of leukemia, lymphoma, or multiple myeloma in this population. DESIGN: We conducted a retrospective case-cohort study in 23,043 uranium miners and identified a total of 177 incident cases of leukemia, lymphoma, and myeloma. Detailed information on occupational radon exposure was obtained for the cases and a randomly selected subcohort of 2,393 subjects. We used the proportional hazards model with power relative risk (RR) function to estimate and test the effects of cumulative radon exposures on incidence rates. RESULTS: Incidence of all leukemia combined and chronic lymphocytic leukemia (CLL) alone was positively associated with cumulative radon exposure. The RR comparing high radon exposure [110 working level months (WLM) ; 80th percentile] to low radon exposure (3 WLM ; 20th percentile) was 1.75 [95% confidence interval (CI) , 1.10-2.78 ; p = 0.014] for all leukemia combined and 1.98 (95% CI, 1.10-3.59 ; p = 0.016) for CLL. Myeloid leukemia and Hodgkin lymphoma were also associated with radon, but RRs were not statistically significant. There was no apparent association of radon with either non-Hodgkin lymphoma or multiple myeloma. Exposure to radon and its progeny was associated with an increased risk of developing leukemia in underground uranium miners. CLL, not previously believed to be radiogenic, was linked to radon exposure. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking may be a risk factor for leukemia. No detailed biological mechanism has been proposed, but a causal link is made plausible by evidence of systemic effects of cigarette smoke and the presence in cigarette smoke of chemicals that have been associated with leukemia risk.Purpose: Our purpose was to investigate the leukemia risk associated with cigarette smoking in a multicenter case-control study of acute leukemias in adults.Methods: Adults aged 18-79 with newly diagnosed leukemia were contacted to participate in this epidemiologic study when they entered a clinical trial to be treated under protocols sponsored by Cancer and Leukemia Group B. Smoking histories for 610 patients with acute leukemia and 618 population control subjects were obtained by telephone interviews. We examined bone marrow samples and classified patients by morphology of leukocyte precursor cells according to the French-American-British (FAB) classification system and, for 378 patients, by the presence or absence of specific clonal chromosome abnormalities. We calculated odds ratios (ORs) for risk of leukemia associated with smoking cigarettes. ORs were adjusted for age, race, and sex.Results: Smoking was associated with only a modest increase in risk for leukemia overall (adjusted OR = 1.13; 95% confidence interval [CI] = 0.89-1.44). However, among participants aged 60 and older, smoking was associated with a twofold increase in risk for acute myeloid leukemia (AML) (OR = 1.96; 95% CI = 1.17-3.28) and a threefold increase in risk for acute lymphocytic leukemia (ALL) (OR = 3.40; 95% CI = 0.97-11.9). Among older persons, risks increased with amount and duration of smoking. Smoking was associated with increased risk for AML classified as FAB type M2 at all ages, with ORs of 1.70 (95% CI = 1.00-2.90) for those younger than 60 and 3.50 (95% CI = 1.53-8.03) for those aged 60 and older. Smoking was also associated with ALL type L2 at all ages, with ORs of 1.72 (95% CI = 0.90-3.27) for those younger than 60 and 5.34 (95% CI = 1.03-27.6) for those who were older. Smoking was more common among patients with specific chromosome abnormalities in AML [-7 or 7q-, -Y, +13] and in ALL [t(9;22)(q34;q11)].Conclusions: Cigarette smoking is associated with increased risk for leukemia and may lead to leukemias of specific morphologic and chromosomal types. The association varies with age.Implication: Examining discrete subtypes of disease may permit more accurate assessment of risk. As standardized morphologic classification and cytogenetic and molecular evaluation of leukemia patients becomes more common, epidemiologic studies that take advantage of these advances will begin to contribute to the identification of additional risk factors and mechanisms in acute leukemia. [ABSTRACT FROM AUTHOR]

Background: The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures., Objective: The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer., Methods: A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors., Results: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9   kg/m 2 (70%). Few (5%) reported any cancer prior to enrollment., Conclusions: The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit several pathways in experimental models of breast carcinogenesis, but epidemiological evidence remains insufficient to support their use for breast cancer prevention. We examined the association between use of NSAIDs and breast cancer risk in a prospective cohort., Methods: The Sister Study is a prospective cohort study of women who had a sister(s) with breast cancer. As of December 2013, 2118 incident breast cancers were ascertained from 50,884 women enrolled between 2003 and 2009. Lifetime history of NSAID use was estimated from self-reported data in pill-years, with 1 pill per week for a year equivalent to 1 pill-year. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer in relation to pill-years of use for different NSAIDs, with adjustment for potential confounders., Results: In the full cohort, although there was some evidence that use of non-aspirin, non-COXib NSAIDs was associated with lower breast cancer risk, there was little evidence of overall association for most categories of NSAID use. Among postmenopausal women NSAID use was not associated with reduced risk of breast cancer. However, among premenopausal women there was significantly reduced risk for any NSAID (HR4vs1=0.66, 95% CI: 0.50-0.87) and specifically for aspirin (HR4vs1=0.57, 95% CI: 0.33-0.98), with small, but non-significant reductions in risk for other drug classes., Conclusion: Women with a sister with breast cancer are themselves at increased risk and might benefit the most from chemoprevention. Although there was little evidence of protective effect from NSAIDs in the overall cohort of women or among the subset who are postmenopausal, there is intriguing evidence that NSAID use, particularly aspirin, may reduce risk among premenopausal women.

Study Question: How well can a single baseline ultrasound assessment of fibroid burden (presence or absence of fibroids and size of largest, if present) predict future probability of having a major uterine procedure?, Summary Answer: During an 8-year follow-up period, the risk of having a major uterine procedure was 2% for those without fibroids and increased with fibroid size for those with fibroids, reaching 47% for those with fibroids ≥ 4 cm in diameter at baseline., What Is Known Already: Uterine fibroids are a leading indication for hysterectomy. However, when fibroids are found, there are few available data to help clinicians advise patients about disease progression., Study Design, Size, Duration: Women who were 35-49 years old were randomly selected from the membership of a large urban health plan; 80% of those determined to be eligible were enrolled and screened with ultrasound for fibroids ≥ 0.5 cm in diameter. African-American and white premenopausal participants who responded to at least one follow-up interview (N = 964, 85% of those eligible) constituted the study cohort. During follow-up (5822 person-years), participants self-reported any major uterine procedure (67% hysterectomies). Life-table analyses and Cox regression (with censoring for menopause) were used to estimate the risk of having a uterine procedure for women with no fibroids, small (<2 cm in diameter), medium (2-3.9 cm), and large fibroids (≥ 4 cm). Differences between African-American and white women, importance of a clinical diagnosis of fibroids prior to study enrollment, and the impact of submucosal fibroids on risk were investigated., Participants/materials, Setting, Methods: There was a greater loss to follow-up for African-Americans than whites (19 versus 11%). For those with follow-up data, 64% had fibroids at baseline, 33% of whom had had a prior diagnosis. Of those with fibroids, 27% had small fibroids (<2 cm in diameter), 46% had medium (largest fibroid 2-3.9 cm in diameter), and 27% had large fibroids (largest ≥ 4 cm in diameter). Twenty-one percent had at least one submucosal fibroid., Main Results and the Role of Chance: Major uterine procedures were reported by 115 women during follow-up. The estimated risk of having a procedure in any given year of follow-up for those with fibroids compared with those without fibroids increased markedly with fibroid-size category (from 4-fold, confidence interval (CI) (1.4-11.1) for the small fibroids to 10-fold, CI (4.4-24.8) for the medium fibroids, to 27-fold, CI (11.5-65.2) for the large fibroids). This influence of fibroid size on risk did not differ between African-Americans and whites (P-value for interaction = 0.88). Once fibroid size at enrollment was accounted for, having a prior diagnosis at the time of ultrasound screening was not predictive of having a procedure. Exclusion of women with a submucosal fibroid had little influence on the results. The 8-year risk of a procedure based on lifetable analyses was 2% for women with no fibroids, 8, 23, and 47%, respectively, for women who had small, medium or large fibroids at enrollment. Given the strong association of fibroid size with subsequent risk of a procedure, these findings are unlikely to be due to chance., Limitations, Reasons for Caution: Despite a large sample size, the number of women having procedures during follow-up was relatively small. Thus, covariates such as BMI, which were not important in our analyses, may have associations that were too small to detect with our sample size. Another limitation is that the medical procedures were self-reported. However, we attempted to retrieve medical records when participants agreed, and 77% of the total procedures reported were verified. Our findings are likely to be generalizable to other African-American and white premenopausal women in their late 30s and 40s, but other ethnic groups have not been studied., Wider Implications of the Findings: Though further studies are needed to confirm and extend the results, our findings provide an initial estimate of disease progression that will be helpful to clinicians and their patients., (Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The purpose of this study was to characterize the operating characteristics of the Personality Assessment Inventory (PAI) validity scales in distinguishing simulators feigning symptoms of traumatic brain injury (TBI) while completing the PAI (n = 84) from a clinical sample of patients with TBI who achieved adequate scores on performance validity tests (n = 112). The simulators were divided into two groups: (a) Specific Simulators feigning cognitive and somatic symptoms only or (b) Global Simulators feigning cognitive, somatic, and psychiatric symptoms. The PAI overreporting scales were indeed sensitive to the simulation of TBI symptoms in this analogue design. However, these scales were less sensitive to the feigning of somatic and cognitive TBI symptoms than the feigning of a broad range of cognitive, somatic, and emotional symptoms often associated with TBI. The relationships of TBI simulation to consistency and underreporting scales are also explored., (© The Author(s) 2014.)

Objectives: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic., Methods: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996., Results: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon., Conclusions: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The purpose of this study was to characterize the relationship between verbal memory and depression scores on the Personality Assessment Inventory following traumatic brain injury. Depression was associated with diminished delayed recall and recognition on the California Verbal Learning Test-II (CVLT-II), even after controlling for a neuropsychological composite score and/or a measure of motivation (i.e., the TOMM). There was no relationship between depression and recall on Verbal Paired Associates or Logical Memory when controlling for the same covariates. The findings were most consistent with depressed subjects failing to utilize the semantic organization of the CVLT-II list to enhance their learning.

Farm children face unique health risks due to sharing their residential environment with hazardous machinery and materials. Causes of mortality among farm children have not been comprehensively described. OBJECTIVE: In the Agricultural Health Study (AHS) cohort, we examined causes of mortality among 21,360 children in Iowa and North Carolina between 1975 and 1998. METHODS: We matched identifying information for children provided by mothers on self-administered questionnaires to state death registries (1975-1998). Data on farm and family characteristics were provided by parents via enrollment questionnaires (1993-1997). Standardized mortality ratios (SMRs) were calculated, using state mortality data to generate expected deaths. We used logistic regression to examine parent, child and farm characteristics associated with injury mortality. RESULTS: There were 162 deaths in Iowa (SMR=0.69; 95% confidence interval (CI)=0.60, 0.81) and 26 deaths in North Carolina (SMR=0.42; 95%CI=0.28, 0.61) in children aged 0-19 years. This deficit was largely due to deaths in the first year of life. Although deaths from overall unintentional injury were not increased, excess agricultural machinery mortality was observed in Iowa (SMR=9.25; 95% CI=5.12, 16.70). In case-control comparisons, maternal age less than 25 years at child's birth (OR=2.17; 95%CI=1.05, 4.49) and having more than 2 children in the family (OR=2.79; 95%CI=1.47, 5.30) were associated with increased child injury mortality. For children under 14 years, participation in farm work was associated with increased risk of agricultural machine-related mortality (OR=3.92; 95% CI=1.04, 14.78). CONCLUSIONS: Parent and child characteristics associated with child injury mortality could be used to target farm safety interventions.

Radon is a well-established cause of lung cancer in miners. Residents of homes with high levels of radon are potentially also at risk. Although most individual studies of indoor radon have failed to demonstrate significant risks, results have generally been consistent with estimates from studies of miners. We studied 1474 incident lung cancer cases aged 40-79 yr in Connecticut, Utah, and southern Idaho. Population controls (n = 1811) were identified by random telephone screening and from lists of Medicare recipients, and were selected to be similar to cases on age, gender, and smoking 10 yr before diagnosis/interview using randomized recruitment. Complete residential histories and information on known lung cancer risk factors were obtained by in-person and telephone interviews. Radon was measured on multiple levels of past and current homes using 12-mo alpha-track etch detectors. Missing data were imputed using mean radon concentrations for informative subgroups of controls. Average radon exposures were lower than anticipated, with median values of 23 Bq/m3 in Connecticut and 45 Bq/m3 in Utah/southern Idaho. Overall, there was little association between time-weighted average radon exposures 5 to 25 yr prior to diagnosis/interview and lung cancer risk. The excess relative risk (ERR) associated with a 100-Bq/m3 increase in radon level was 0.002 (95% CI -0.21, 0.21) in the overall population, 0.134 (95% CI -0.23, 0.50) in Connecticut, and -0.112 (95% CI -0.34, 0.11) in Utah/Idaho. ERRs were higher for some subgroups less prone to misclassification, but there was no group with a statistically significant linear increase in risk. While results were consistent with the estimates from studies of miners, this study provides no evidence of an increased risk for lung cancer at the exposure levels observed.

Occupational and industrial exposures have been implicated in the etiology of leukemia, yet uncertainty remains regarding potential high risk occupations. We examined the associations between self-reported occupations and hobbies and acute leukemia risk using data from 811 cases and 637 controls participating in a case-control study in the U.S. and Canada. We found that several occupations may increase the risk of acute leukemia, particularly occupations related to petroleum products, rubber, nuclear energy, munitions, plastics, and electronics manufacturing. Differences were noted according to histological type. Other occupations and hobbies were not clearly associated with risk.

Parental exposure to pesticides may contribute to childhood cancer risk. Through the Agricultural Health Study, a prospective study of pesticide applicators in Iowa and North Carolina, we examined childhood cancer risk and associations with parental pesticide application. Identifying information for 17,357 children of Iowa pesticide applicators was provided by parents via questionnaires (1993-1997) and matched against the Iowa Cancer Registry. Fifty incident childhood cancers were identified (1975-1998). Risk of all childhood cancers combined was increased [standardized incidence ratio (SIR) = 1.36; 95% confidence interval (CI), 1.03-1.79]. Risk of all lymphomas combined was also increased (SIR = 2.18; 95% CI, 1.13-4.19), as was risk of Hodgkin's lymphoma (SIR = 2.56; 95% CI, 1.06-6.14). We used logistic regression to explore associations between self-reported parental pesticide application practices and childhood cancer risk. No association was detected between frequency of parental pesticide application and childhood cancer risk. An increased risk of cancer was detected among children whose fathers did not use chemically resistant gloves [odds ratio (OR) = 1.98; 95% CI, 1.05-3.76] compared with children whose fathers used gloves. Of 16 specific pesticides used by fathers prenatally, ORs were increased for aldrin (OR = 2.66), dichlorvos (OR = 2.06), and ethyl dipropylthiocarbamate (OR = 1.91). However, these results were based on small numbers and not supported by prior biologic evidence. Identification of excess lymphoma risk suggests that farm exposures including pesticides may play a role in the etiology of childhood lymphoma.

Background: The ubiquitous dichlorodiphenyltrichloroethane (DDT) metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) is an androgen receptor antagonist. Data on potential antiandrogenic activity of DDE in humans are limited., Methods: The relations between concentrations of plasma DDE and several serum androgens (total testosterone, bioavailable testosterone, 5alpha-dihydrotestosterone, and free androgen index) were examined in 137 North Carolina black male farmers, using multiple linear regression., Results: Participants ranged in age from 30 to 88 years (mean = 62 years). Most had farmed for about 30 years and 27% reported having used DDT. The median DDE level was 7.7 microg per liter (1213 microg per kg lipid), slightly higher than in other recent studies. Overall, concentrations of DDE and androgens were unrelated. Total testosterone decreased 2% (95% confidence limits [CL] = -9%, 5%) per increase in interquartile distance of lipid-adjusted DDE. The percentage change in other hormones was similarly negligible. However, among those whose DDE level was in the top tenth percentile, compared with all others, total testosterone and free androgen index were lower by 23% (CL= -40%, 1%) and 22% (CL =-41%, 4%) respectively. Plasma androgen levels decreased with age, a relation that has previously been studied only in whites., Conclusions: Studies of more highly exposed populations may be needed to evaluate effects, if any, of DDE.

Background: Health effects of pesticides have not been well studied in black farmers. We describe agricultural practices and pesticide-related symptoms in North Carolina black and white farmers participating in the Agricultural Health Study., Methods: Self-administered questionnaires were completed by 891 black and 11,909 white farmers licensed to apply restricted pesticides. Regression models were used to compare characteristics by race., Results: Black farmers reported lower lifetime pesticide use, less use of each class of pesticides (e.g., herbicides, insecticides), less use of high exposure application methods, and fewer pesticide-related symptoms such as headaches or dizziness, skin irritation, chest discomfort and feeling nervous or depressed than did white farmers., Conclusions: Differences between black and white farmers may be explained by farm characteristics or economics. Despite lower use of pesticides, black farmers may have other work practices that affect exposure and risk.

Ethylene oxide is a gas used in some dental offices to sterilize equipment. In pregnant laboratory animals, ethylene oxide increases malformations and feral loss. Increased gestation length has also been reported. In humans, two studies have reported increased spontaneous abortions among ethylene oxide-exposed women, but few other data exist. We sent questionnaires to 7,000 dental assistants, age 18-39 years, registered in California in 1987; 4,856 responded (69%). We based our analysis on 1,320 women whose most recent pregnancy was conceived while working full-time. Thirty-two women reported exposure to ethylene oxide; unexposed dental assistants comprised the comparison group. We estimated relative risks of spontaneous abortion and preterm birth using a person-week model. We estimated relative risks of postterm birth (> or = 42 weeks) and a combined adverse outcomes model using logistic regression. Among exposed women, the age-adjusted relative risk of spontaneous abortion was 2.5 [95% confidence interval (CI) = 1.0-6.3], for preterm birth 2.7 (95% CI = 0.8-8.8), and for postterm birth 2.1 (95% CI = 0.7-5.9). The estimated relative risk of any of these adverse outcomes among exposed women was 2.5 (95% CI = 1.0-6.1) after adjusting for age, nitrous oxide, and number of mercury amalgams prepared. These data further implicate ethylene oxide as a possible reproductive toxicant in humans.

Background: The glutathione S-transferases (GST) mediate exposure to various cytotoxic and genotoxic agents, including those associated with increased risk of the myelodysplastic syndromes (MDS). Both GST M1 (GSTM1) and GST theta 1 (GSTT1) genes have a "null" variant allele, in which the entire gene is absent. We tested whether the homozygous null genotype of GSTM1 and GSTT1 altered the risk for MDS., Methods: In a hospital-based case-control study we analysed lymphocyte or bone-marrow DNA samples from 96 patients with MDS and 201 cancer-free controls of similar age, race, and sex. We have restricted our report to the 92 white MDS patients. We analysed GSTM1 and GSTT1 genotypes by PCR., Findings: The frequency of the GSTT1 null genotype was higher among MDS cases (46%) than among controls (16%). Inheritance of the GSTT1 null genotype conferred a 4.3-fold of MDS (odds ratio 4.3, 95% CI 2.5-7.4, p < 0.00001). The GSTM1 null genotype was not associated with increased risk of MDS (odds ratio 0.8, 0.5-1.3)., Interpretation: Individuals with the GSTT1 null genotype may have enhanced susceptibility to MDS. The mechanism might involve decreased detoxification of environmental or endogenous carcinogens.

The relation between anesthetic gas exposure and spontaneous abortion remains unresolved. We examined the effect of nitrous oxide on spontaneous abortion among female dental assistants. Questionnaires were sent to 7,000 dental assistants aged 18-39 years who were registered in California in 1987; 4,856 (69%) responded. Analysis was based on 1,465 respondents whose most recent pregnancy was conceived while working full time. Women were asked how many hours a week they worked with nitrous oxide during this pregnancy and whether the excess gas was scavenged (vented). Relative risk of spontaneous abortion (through week 20) was calculated using a person-week model. This allowed women with current pregnancies (13%) or induced abortions (10%) to be included for appropriate time periods of risk. A total of 101 pregnancies (7%) ended as spontaneous abortions. An elevation in risk of spontaneous abortion was seen among women who worked with nitrous oxide for 3 or more hours per week in offices not using scavenging equipment (relative risk = 2.6, 95% confidence interval 1.3-5.0, adjusted for age, smoking, and number of amalgams prepared per week), but not among those using nitrous oxide in offices with scavenging equipment. This relation changed little when analyses were restricted to confirmed pregnancies or examined for several types of potential bias. Scavenging equipment appears to be important in protecting the reproductive health of women working with nitrous oxide.

Exposure to mercury vapour or inorganic mercury compounds can impair fertility in laboratory animals. To study the effects of mercury vapour on fertility in women, eligibility questionnaires were sent to 7000 registered dental assistants in California. The final eligible sample of 418 women, who had become pregnant during the previous four years, were interviewed by telephone. Detailed information was collected on mercury handling practices and the number of menstrual cycles without contraception it had taken them to become pregnant. Dental assistants not working with amalgam served as unexposed controls. Women with high occupational exposure to mercury were less fertile than unexposed controls. The fecundability (probability of conception each menstrual cycle) of women who prepared 30 or more amalgams per week and who had five or more poor mercury hygiene factors was only 63% of that for unexposed women (95% CI 42%-96%) after controlling for covariates. Women with low exposure were more fertile, however, than unexposed controls. Possible explanations for the U shaped dose response and limitations of the exposure measure are discussed. Further investigation is needed that uses biological measures of mercury exposure.

Possible associations between location of residence and acute leukemia risk were investigated in a study of 610 newly diagnosed patients, aged 18-79 y, and 618 population controls. There was an association between ever living within 5 miles (8 km) of an industrial plant and leukemia risk, with adjusted odds ratios (ORs) of 1.4 (95% confidence interval [95% CI] = 1.0-1.9) for all acute leukemias combined, 1.4 (95% CI = 1.0-2.0) for acute myeloid leukemia, and 1.7 (95% CI = 1.0-2.7) for acute lymphocytic leukemia. Odds ratios increased with decreasing distance from industrial sites, but a gradient with duration of residence was seen only among those less than age 60 who had lived within a mile of any industry. Suggestive associations were also observed for residence near specific industries, but the number of individuals living near any one industry was small.

Background: Workers who sprayed phenoxy acid herbicides, especially those who sprayed before 1975, may have been exposed to significant amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent animal carcinogen present in herbicide preparations as a contaminant., Purpose: The aims of this study were (a) to determine serum levels of TCDD in a representative sample of workers occupationally exposed to the agent during the spraying of phenoxy acid herbicides; (b) to compare serum levels in workers exposed before 1965, when concentrations in herbicide products were unregulated and high, with levels in workers exposed after 1974, when concentrations were lower as a result of government regulations worldwide; and (c) to examine the correlation, if any, between serum levels and duration of employment in spraying., Methods: Thirty-seven subjects were randomly selected from a group of 654 men who had sprayed the herbicides 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) in Australia for at least 12 months. The workers were classified as follows: eight who sprayed only before 1965, nine who sprayed only during the period after 1964 and before 1975, and 20 who sprayed during the period after 1974 and before 1991. Serum from the workers was analyzed for TCDD by high-resolution gas chromatography and high-resolution mass spectrometry at a detection limit of 0.6 parts per trillion (ppt) on a lipid-weight basis. In addition, rates of exposure to TCDD were estimated, as were TCDD serum concentrations at termination of employment and intensity of herbicide use., Results: Only one worker, with a serum TCDD level of 34 ppt, had a serum level higher than the maximum level of 26 ppt reported for the general population. Assuming a half-life of 7.1 years, we estimated the mean exposure rates to be 2.7, 2.3, and 0.06 ppt/mo for the three epochs, respectively. We found the highest serum level of TCDD at the time of cessation of employment to be 329 ppt. Calendar period and intensity of use of 2,4,5-T and 2,4-D were statistically significant determinants of rate of exposure to TCDD, but 2,4-D was associated with exposure rate only for the pre-1975 periods. Estimated rates prior to 1965 were more than an order of magnitude higher than those after 1974., Conclusion: The highest estimated exposure rate was 20.7 ppt/mo, which suggests that some sprayers may have been exposed to levels comparable with those that produce cancer in laboratory animals.

Background: Epidemiologic studies of acute myeloid leukemias (AMLs) show small increases in risk of disease associated with certain occupations and chemical exposures., Purpose: This study was designed to determine whether the presence of mutationally activated ras oncogenes in AML are associated with occupational and chemical exposures., Methods: We interviewed 62 patients with newly diagnosed AML (or their next-of-kin), all of whom were enrolled in a national multicenter clinical trial, and 630 healthy control subjects. DNA extracted from patients' pretreatment bone marrow samples was amplified by using the polymerase chain reaction and probed with allele-specific oligonucleotides for activating point mutations at the 12th, 13th, and 61st codons of three protooncogenes: H-ras (also known as HRAS), K-ras (also known as KRAS2), and N-ras (also known as NRAS)., Results: Patients with ras mutation-positive AML had a higher frequency (six of 10 patients) of working 5 or more years in an a priori high-risk occupation than did patients with ras mutation-negative AML (eight of 52; odds ratio [OR] = 6.8; 95% confidence interval [CI] = 1.3-36). Patients with ras mutation-positive AML were more likely than patients with ras mutation-negative AML to have breathed chemical vapor on the job (OR = 9.1; 95% CI = 1.3-64) or to have had skin contact with chemicals (OR = 6.9; 95% CI = 1.3-37). When ras-positive patients were compared with healthy control subjects, the ORs for occupation and occupational exposures remained elevated, while patients with ras mutation-negative AML showed no increased risk when compared with control subjects., Conclusion: Activation of ras proto-oncogenes may identify an etiologic subgroup of AML caused by occupation and chemical exposure., Implication: Disease etiology may be better understood if epidemiologic measures of exposure are integrated with molecular assays of the genetic defects responsible for cancer initiation and promotion.

Vocational functioning at least 2 years postinjury was examined in a group of 57 severely closed-head injured (CHI) patients and 50 nonbrain-injured spinal-cord injured (SCI) patients. The two groups were equated on the following preinjury parameters: age, education, socioeconomic status (SES), male/female ratio, and marital status. The CHI and SCI patients had a similar number of members who were employed at follow-up. However, mean follow-up socioeconomic status was significantly lower in the CHI group and premorbidly employed CHI patients suffered a greater loss of SES than did premorbidly employed SCI patients. These results indicate that the degree of vocational impairment after severe CHI goes beyond impairment seen with another chronic disabling condition (i.e., SCI) that is associated with severe physical impairment but not neuropsychological impairment. In the CHI group, the following variables were all correlated with SES at follow-up: preinjury education, posttraumatic amnesia duration, degree of neuropsychological impairment soon after injury, and emotional adjustment at follow-up.

Background: Fertility is reduced in female rats exposed to levels of nitrous oxide similar to those found in some dental offices. Epidemiologic studies have suggested an association between exposure to mixed anesthetic gases and impaired fertility. We investigated the effects of occupational exposure to nitrous oxide on the fertility of female dental assistants., Methods: Screening questionnaires were mailed to 7000 female dental assistants, ages 18 to 39, registered by the California Department of Consumer Affairs. Sixty-nine percent responded. Four hundred fifty-nine women were determined to be eligible, having become pregnant during the previous four years for reasons unrelated to the failure of birth control, and 91 percent of these women completed telephone interviews. Detailed information was collected on exposure to nitrous oxide and fertility (measured by the number of menstrual cycles without contraception that the women required to become pregnant)., Results: After controlling for covariates, we found that women exposed to high levels of nitrous oxide were significantly less fertile than women who were unexposed or exposed to lower levels of nitrous oxide. The effect was evident only in the 19 women with five or more hours of exposure per week. These women were only 41 percent (95 percent confidence interval, 23 to 74 percent; P less than 0.003) as likely as unexposed women to conceive during each menstrual cycle., Conclusions: Occupational exposure to high levels of nitrous oxide may adversely affect women's ability to become pregnant.

The validity of self-reports of 48 adults with mental retardation of daily living competency using the recently revised Vineland Adaptive Behavior Scales (Sparrow, Balla, & Cicchetti, 1984) was investigated. Self-report was compared to standard Vineland interviews of subjects' program counselors and to demonstrated competency in a real-life setting. On domains measuring adaptive skills, the subject and counselor interviews yielded highly consistent results. On the optional Maladaptive Behavior domain, however, the subjects with mental retardation underreported problematic behavior. Response validity and implications for use of self-report for program planning and placement decisions were discussed.

Mortality associated with passive smoking was evaluated in a 12-year study of 27,891 White adult smokers and 19,035 never smokers identified in 1963. Death rates were calculated using an estimate of the person-years at risk. Adjusted for age, marital status, education, and quality of housing, the estimated relative risks of death from all causes were 1.17 (approximate 95% confidence interval 1.01, 1.36) for men and 1.15 (1.06, 1.24) for women with passive exposure. These relative risks were similar to those for ex-smokers and for pipe or cigar smokers. Risks increased slightly with level of exposure. The relative risk from passive smoking was greatest for men under age 50 (RR = 2.09, 1.31-3.34). Risks from passive smoking were slightly elevated for several causes among men and women, and may be broader than those previously reported. On the other hand, these small nonspecific increases in death rates may reflect other characteristics of passive smokers that increase mortality.

A surveillance system is proposed to detect an increase in the mean of a Poisson distribution of cases of a disease. This system, called short memory (SM), is based on conditional binomial tests which are performed sequentially at fixed time intervals. The probability of rejection at each test defines the run length distribution which has a geometric tail. A standard SM scheme outperforms other SM schemes. The CUSUM outperforms the SM schemes when the baseline mean is specified correctly. This type of misspecification does not affect the SM scheme.

Pregnant Sprague-Dawley and Fisher 344 rats were treated on day 15 of gestation with Aroclor 1254 in a single dose ranging from 0 to 500 mg kg-1 body weight and killed on day 18 of gestation. In the small groups of animals used for this study, no effect was observed on mean maternal liver or placental weight, or the number of fetal resorptions at any of the doses tested. Measurement of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7ECD) activity in tissue homogenates, however, showed that administration of Aroclor 1254 (15 mg kg-1 body weight or greater) induced mono-oxygenase activity in fetal liver. Both the AHH and 7ECD assay detected effects of PCBs with similar sensitivity, and the findings were comparable when homogenates were assayed instead of microsomes. These data were used to suggest technical approaches to the detection of mono-oxygenase induction in placental tissue human populations exposed to PCBs.

A case control study was conducted in North Carolina to explore the relation between individual exposure to sunlight and the risk of cataracts. One hundred thirteen cases and 161 controls aged 40-69 at diagnosis were studied. Sunlight exposure was inferred from interview data on residency and time spent in the sun, combined with solar radiation data from the National Climatic Data Center. Sunlight exposure was very slightly related to all types of opacities combined. Although the numbers of cases with each type of opacity was small, the risk of cataracts was slightly increased in medium and high exposure categories for persons having cortical or posterior subcapsular opacities only, but not nuclear sclerotic changes. Persons with dark brown or hazel eyes are at increased risk. An unexpected finding was that persons who reported using tranquilizers for six months were at increased risk.

Evaluation of adult health risks from exposures that occurred in childhood may require case-control studies in which subjects who are now adults are asked to provide information that might be more accurately provided by their parents. The quality of parental smoking and drinking histories provided by adult offspring was evaluated in a North Carolina study of cancer risk from childhood exposure to cigarette smoke. A total of 1,036 adult subjects aged 15-59 years were asked about parents' smoking and drinking habits during the subject's childhood and prior to the subject's birth. Parents or siblings of 70% of the study subjects were also interviewed to obtain the same information. Subjects were generally able to provide information on parents' smoking habits, although they were less able to answer questions requiring knowledge of dates or amounts. Accuracy of information provided, as measured by agreement between subjects and mothers or between subjects and siblings, was also good for many simple exposure questions. Age and race influenced the proportion of subjects able to provide information but did not affect the quality of data. Case-control status and habits of parents had an effect on agreement between subjects and mothers for some questions but had no overall effect on the quality or interpretation of data. Cigar smoking and alcohol consumption were not reported as completely or accurately as cigarette smoking. Overall, this study demonstrated the feasibility of evaluating effects of some childhood exposures by obtaining exposure information from individuals who are now adults. Data from such studies can be used to distinguish exposed from nonexposed subjects but cannot readily be used to estimate level of exposure.

This study examined selective reminding and recognition memory performance of 21 severe closed-head injured patients tested within 6 months of regaining consciousness and then again after at least 1 year. Performances on selective reminding parameters were highly correlated and patients performed significantly worse at both testings than did hospitalized controls matched for age, education, and sex. Patients improved from testing 1 to testing 2 on only four of six memory variables. Average Impairment Rating at testing 1 was a marginally better predictor of memory performance at testing 2 than was length of coma. Results are discussed in terms of (a) utility of selective reminding parameters and predictors of outcome and (b) dissociations in recovery of memory parameters.

With data that were obtained in a private census in Washington County, Maryland, in 1963, the prevalence of household exposure to tobacco smoke was determined, and factors associated with passive smoke exposure were identified among 48,342 white adults. In 1963, 52% of men and 72% of women were exposed to smoke from others at home. Smokers of both sexes were more likely to live with other smokers than were nonsmokers. However, 30% of men who never smoked and 64% of women who never smoked lived with smokers. Marriage was a primary determinant of exposure for women but not for men, with 75% of married women who did not smoke exposed but only 38% of unmarried women who did not smoke exposed. Conversely, among men who did not smoke, exposure was more common among those who were not married than among those who were married. After control for other factors associated with exposure, exposure prevalence increased with years of school among men who did not smoke but decreased with years of school among women who did not smoke. Exposure prevalence also varied slightly with housing quality and location of residence. Smoking by spouse was an accurate reflection of household exposure for women but not for men; 88% of the exposure among women who did not smoke was contributed by the spouse, whereas only 62% of exposure among men who did not smoke was from the spouse.

Colorectal cancer incidence rates for smokers, nonsmokers living with smokers (i.e., passive smokers), and nonsmokers in smoke-free households were compared in a 12-year prospective study of 25,369 women who participated in a private census conducted in Washington County, MD, in 1963. Women who smoked had a decreased relative risk of colorectal cancer compared with the risk for nonsmokers (age-adjusted relative risk, 0.76; 95% confidence interval, 0.52-1.10). The risk for passive smokers was similar to that for smokers. The relative risks were significantly reduced for older women; relative risks were 0.42 for smokers and 0.66 for passive smokers over age 65. The data suggest that older women who smoke have a lower risk of colorectal cancer than nonsmokers. The effect may be mediated by an antiestrogenic effect of smoking.

This study indicates that the Lachar MMPI interpretation system is useful in this setting. Overall and specific paragraph accuracy for 98 psychiatric patients' reports suggest clinician acceptance, diagnostic utility, and the potential realization of time savings for the psychologist.