Tuberculous sacroiliitis in a patient with systemic lupus erythematosus: a case report and literature review.

Systemic lupus erythematosus (SLE) patients are at higher risk of developing opportunistic infections such as tuberculosis (TB), especially extrapulmonary forms like osteoarticular TB, compared to the general population. However, tuberculous sacroiliitis has been scarcely reported in these patients. We present a 34-year-old woman with SLE who developed articular tuberculosis simultaneously affecting the right sacroiliac joint and the left knee. The patient was successfully treated with antituberculosis therapy for nine months. In this case, in addition to the immunological abnormalities of lupus, the long-term glucocorticoid therapy at high dosages was the main risk factor for the development of osteoarticular tuberculosis.

Correlated response in litter size components in rabbits selected for litter size variability.

A divergent selection experiment for the environmental variability of litter size (Ve) over seven generations was carried out in rabbits at the University Miguel Hernández of Elche. The Ve was estimated as the phenotypic variance within the female, after correcting for year-season and parity-lactation status. The aim of this study was to analyse the correlated responses to selection in litter size components. The ovulation rate (OR) and number of implanted embryos (IE) in females were measured by laparoscopy at 12 day of the second gestation. At the end of the second gestation, the total number of kits born was measured (TB). Embryonic (ES), foetal (FS) and prenatal (PS) survival were computed as IE/OR, TB/IE and TB/OR, respectively. A total of 405 laparoscopies were performed. Data were analysed using Bayesian methodology. The correlated response to selection for litter size environmental variability in terms of the litter size components was estimated as either genetic trends, estimated by computing the average estimated breeding values for each generation and each line, or the phenotypic differences between lines. The OR was similar in both lines. However, after seven generations of selection, the homogenous line showed more IE (1.09 embryos for genetic means and 1.23 embryos for phenotypic means) and higher ES than the heterogeneous one (0.07 for genetic means and 0.08 for phenotypic means). The probability of the phenotypic differences between lines being higher than zero (p) was 1.00 and .99, respectively. A higher uterine overcrowding of embryos in the homogeneous line did not penalize FS; as a result, this line continued to show a greater TB (1.01 kits for genetic means and 1.30 kits for phenotypic means, p = .99, in the seventh generation). In conclusion, a decrease in litter size variability showed a favourable effect on ES and led to a higher litter size at birth.

Prospective study of chemical exposures and amyotrophic lateral sclerosis.

BACKGROUND: Although environmental toxins, including pesticides, are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), no data exist from large prospective investigations. This study assessed the association between exposure to chemicals and risk of ALS in a prospective cohort study. METHODS: The relation between self-report of regular exposure to 11 different chemical classes or x rays and ALS mortality among over 1 million participants in the American Cancer Society's Cancer Prevention Study II was prospectively assessed. Follow-up from 1989 through 2004 identified 617 deaths from ALS among men and 539 among women. Adjusted rate ratios (RR) were calculated using Cox proportional hazards. RESULTS: The RR for ALS mortality among individuals exposed to pesticides/herbicides compared with that among unexposed individuals was 1.07 (95% CI 0.79 to 1.44), but somewhat higher after excluding those with missing duration of pesticides exposure (RR 1.44; 95% CI 0.89 to 2.31; p = 0.14). A non-significant increase in ALS mortality was found among individuals who reported exposure to formaldehyde (RR 1.34; 95% CI 0.93 to 1.92). Excluding those with a missing duration of formaldehyde exposure, the RR was 2.47 (95% CI 1.58 to 3.86), and there was a strongly significant dose-response relation with increasing years of exposure (p trend = 0.0004). CONCLUSIONS: There was little evidence for any association between pesticides/herbicide exposure and ALS. In contrast, evidence was found, suggesting an increased risk of ALS with formaldehyde exposure. Because of the longitudinal design, this result is unlikely to be due to bias, but it should nevertheless be interpreted cautiously and needs to be verified independently.

Temporal relationship between cigarette smoking and risk of Parkinson disease.

OBJECTIVE: To characterize further the relationship between smoking history and Parkinson disease (PD) risk by considering temporal and qualitative features of smoking exposure, including duration, average intensity, and recentness, as well as the relative importance of smoking during different periods of life. METHODS: We prospectively assessed incident PD from 1992 to 2001 among 79,977 women and 63,348 men participating in the Cancer Prevention Study II Nutrition Cohort, according to their cigarette smoking status and lifetime smoking histories. RESULTS: During follow-up, 413 participants had definite or probable PD confirmed by their treating neurologists or medical record review. Compared with never smokers, former smokers had a relative risk (RR) of 0.78 (95% CI 0.64 to 0.95) and current smokers had an RR of 0.27 (95% CI 0.13 to 0.56). On average, participants with more years smoked, more cigarettes per day, older age at quitting smoking, and fewer years since quitting smoking had lower PD risk. The relative risks and trends did not vary significantly by sex. The cumulative incidence of PD was lowest among participants who quit smoking at later ages. A 30% to 60% decreased risk of PD was apparent for smoking as early as 15 to 24 years before symptom onset, but not for smoking 25 or more years before onset. CONCLUSIONS: The lower risk of Parkinson disease among current and former smokers varied with smoking duration, intensity, and recentness. The dependence of this association on the timing of smoking during life is consistent with a biologic effect.

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Prospective study of occupation and amyotrophic lateral sclerosis mortality.

Occupational exposures are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), but results of epidemiologic studies have been inconsistent. The authors prospectively assessed the relation between occupation and ALS mortality among more than 1 million participants in the Cancer Prevention Study II of the American Cancer Society. Follow-up from 1989 through 2002 identified 507 ALS deaths among men and 430 among women. Adjusted rate ratios were calculated by using Mantel-Haenszel weights and Cox proportional hazards. Among men, elevated ALS mortality was found for programmers (rate ratio = 4.55, 95% confidence interval: 1.46, 14.2; p = 0.009) and laboratory technicians (rate ratio = 1.96, 95% confidence interval: 1.04, 3.66; p = 0.04). Occupations previously associated with increased risk of ALS for which no increased risk was found included farmers, electricians, and welders, although the numbers of electricians (eight ALS deaths) and welders (two ALS deaths) were small. Among women, only machine assemblers had significantly increased ALS mortality (rate ratio = 2.81, 95% confidence interval: 1.05, 7.53; p = 0.04). Results, which suggest that male programmers and laboratory technicians and female machine assemblers may be at increased risk of death from ALS, should be interpreted cautiously, however, because they are based on small numbers.

Prospective study of military service and mortality from ALS.

BACKGROUND: Two recent studies suggest that the risk of ALS is increased among Gulf War veterans. It is not known whether military service outside of the Gulf War is associated with increased risk of ALS. METHODS: The authors prospectively assessed the relation between service in the military and ALS mortality among participants in the Cancer Prevention Study II cohort of the American Cancer Society, a cohort that includes over 500,000 men from the 50 states, Washington, DC, and Puerto Rico. Participant follow-up was conducted from 1989 through 1998 for ALS mortality. There were a total of 280 deaths from ALS among 126,414 men who did not serve in the military and 281,874 who did. Adjusted relative risks (RRs) were calculated using Mantel-Haenszel weights and Cox proportional hazards. RESULTS: Men who served in the military had an increased death rate from ALS (RR = 1.53; 95% CI: 1.12 to 2.09; p = 0.007) compared with those who did not serve. The increase in ALS mortality was observed among men who served in the Army or National Guard (RR = 1.54), Navy (RR = 1.87), Air Force (RR = 1.54), and Coast Guard (RR = 2.24); no increase in risk was found in men who served in the Marine Corps, although there were only 13,670 men in this group. The risk of ALS among men who served was elevated in every 5-year birth cohort from 1915 through 1939. CONCLUSIONS: Military personnel have an increased risk of ALS. This increase appeared to be largely independent of the branch of service and the time period served.

Prospective study of cigarette smoking and amyotrophic lateral sclerosis.

Cigarette smoking has been proposed as a risk factor for amyotrophic lateral sclerosis (ALS), but because of the low incidence of ALS this association has been examined only with case-control methods. The authors prospectively assessed the relation between cigarette smoking and ALS mortality among participants in the Cancer Prevention Study II cohort of the American Cancer Society, a cohort of over 1 million people enrolled in 1982 who completed a lifestyle questionnaire including a detailed smoking history at baseline. Causes of deaths were ascertained through death certificates; ALS was not identified separately until 1989. From January 1, 1989, through 1998, 291 women and 330 men died from ALS. The relative risk of ALS among current smokers compared with never smokers was 1.67 (95% confidence interval: 1.24, 2.24; p = 0.002) in women and 0.69 (95% confidence interval: 0.49, 0.99; p = 0.04) in men. The difference in the relative risk estimates between the sexes was statistically significant (p < 0.0003). This large prospective study provides limited evidence that current cigarette smoking may be associated with increased death rates from ALS in women but not in men.

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

A prospective study of diet and stomach cancer mortality in United States men and women.

Frequent consumption of fruits, vegetables, and whole grains has been associated with a reduced risk of stomach cancer in the majority of case-control studies of these factors: however, prospective studies have been less consistent. We examined the association between selected major food groups (citrus fruits, vegetables, whole grains, and processed meats) and risk of fatal stomach cancer in the Cancer Prevention Study (CPS) II cohort of 1.2 million United States men and women. During 14 years of follow-up, we documented 439 stomach cancer deaths in women and 910 in men after exclusion of individuals with prevalent cancers, inadequate diet information, and recent weight loss at baseline in 1982. After controlling for other risk factors, none of the food groups examined were associated with risk of stomach cancer except for an unexpected increased risk with vegetable consumption in women [relative risk (RR) = 1.25; 95% confidence interval (CI), 0.99-1.58; highest versus lowest tertile, P = 0.06 for trend]. A high overall plant food intake (a sum of vegetables, citrus fruit, and whole grains) was associated with reduced risk in men (RR = 0.79; 95% CI, 0.67-0.93; highest versus lowest tertile, P = 0.003 for trend), but not in women (RR = 1.18; 95% CI, 0.93-1.50; P = 0.16 for trend). Of individual foods examined, liver consumption greater than twice/week was associated with an increased risk of fatal stomach cancer in women (RR = 1.96; 95% CI, 1.09-3.53) and men (RR = 1.63; 95% CI, 1.02-2.62) compared with nonconsumers. This study supports a modest role for plant foods in reducing the risk of fatal stomach cancer in men, but not in women.

Ligand binding to transmembrane receptors on intact cells or membrane vesicles measured in a homogeneous 1-microliter assay format.

We have developed homogeneous miniaturized assays to measure ligand binding to either intact cells or receptor-containing membrane fragments by analysis of particle brightness. As an example, the affinities and inhibition constants of fluorescently labeled interleukin-8 (IL-8) and a low-molecular-weight antagonist toward the receptors CXCR1 and CXCR2, which belong to the superfamily of G protein-coupled receptors (GPCRs), were determined. Although the results were generally comparable between the two approaches, the cell-based measurements revealed a more complex pattern of both ligand and inhibitor titration curves, pointing to the influence of intracellular regulatory events. Both the vesicle- and cell-based membrane receptor assays were successfully miniaturized to a total volume of 1 microl without compromising their sensitivity, indicating that screening of transmembrane receptors in these formats is feasible. This is the first report of a cellular ligand-binding assay performed in such low volumes. The resulting savings in reagent could potentially enable the use of primary cells for future HTS/ultra-HTS efforts.

Determinants of DNA yield and quality from buccal cell samples collected with mouthwash.

Buccal cells are becoming an important source of genomic DNA in epidemiological studies, but little is known about the effect of different sampling conditions on DNA quality and yield. We used a mouthwash protocol to collect six daily buccal cell samples from 35 healthy volunteers. Twenty-four individuals (six men and 18 women) correctly completed the protocol and were included in paired analyses to determine whether "swish" time (30 s versus 60 s), toothbrushing before collection, or lag time between collection and DNA extraction (1 day versus 5, 10, or 30 days at room temperature) would affect sample quality and yield. Total DNA, human-specific DNA (hDNA), degradation of DNA, and ability to amplify by PCR were determined. hDNA yield did not significantly vary by "swish" time. However, toothbrushing 1 h before sample collection reduced the amount of hDNA by nearly 40% (34 microg versus 21 microg; P = 0.06). Median hDNA yields for samples that were held for 1, 5, 10, and 30 days before extraction were 32 microg (range, 4-196), 32 microg (2-194), 23 microg (3-80), and 21 microg (5-56), respectively. The 10- and 30-day samples had significantly less hDNA than those processed after 1 day (P = 0.01). PCR success rates for beta-globin gene fragments of length 268 bp, 536 bp, and 989 bp were 94% or better, and high molecular weight DNA (>23 kb) was found in all but one sample. These results suggest that buccal cells should be collected before brushing teeth and processed within 5 days of collection to maximize hDNA yield.

In early development of the rat mRNA for the major myelin protein P(0) is expressed in nonsensory areas of the embryonic inner ear, notochord, enteric nervous system, and olfactory ensheathing cells.

The myelin protein P(0) has a major structural role in Schwann cell myelin, and the expression of P(0) protein and mRNA in the Schwann cell lineage has been extensively documented. We show here, using in situ hybridization, that the P(0) gene is also activated in a number of other tissues during embryonic development. P(0) mRNA is first detectable in 10-day-old embryos (E10) and is at this time seen only in cells in the cephalic neural crest and in the otic placode/pit. P(0) expression continues in the otic vesicle and at E12 P(0) expression in this structure largely overlaps with expression of another myelin gene, proteolipid protein. In the developing ear at E14, P(0) expression is complementary to expression of serrate and c-ret mRNAs, which later are expressed in sensory areas of the inner ear, while expression of bone morphogenetic protein (BMP)-4 and P(0), though largely complementary, shows small areas of overlap. P(0) mRNA and protein are detectable in the notochord from E10 to at least E13. In addition to P(0) expression in a subpopulation of trunk crest cells at E11/E12 and in Schwann cell precursors thereafter, P(0) mRNA is also present transiently in a subpopulation of cells migrating in the enteric neural crest pathway, but is down-regulated in these cells at E14 and thereafter. P(0) is also detected in the placode-derived olfactory ensheathing cells from E13 and is maintained in the adult. No signal is seen in cells in the melanocyte migration pathway or in TUJ1 positive neuronal cells in tissue sections. The activation of the P(0) gene in specific tissues outside the nervous system was unexpected. It remains to be determined whether this is functionally significant, or whether it is an evolutionary relic, perhaps reflecting ancestral use of P(0) as an adhesion molecule.

Amino acid nitrosation products as alkylating agents.

Nitrosation reactions of alpha-, beta-, and gamma-amino acids whose reaction products can act as alkylating agents of DNA were investigated. To approach in vivo conditions for the two-step mechanism (nitrosation and alkylation), nitrosation reactions were carried out in aqueous acid conditions (mimicking the conditions of the stomach lumen) while the alkylating potential of the nitrosation products was investigated at neutral pH, as in the stomach lining cells into which such products can diffuse. These conclusions were drawn: (i) The alkylating species resulting from the nitrosation of amino acids with an -NH(2) group are the corresponding lactones; (ii) the sequence of alkylating power is: alpha-lactones > beta-lactones > gamma-lactones, coming respectively from the nitrosation of alpha-, beta-, and gamma-amino acids; and (iii) the results obtained may be useful in predicting the mutagenic effectiveness of the nitrosation products of amino acids.

Cigarette smoking and diabetes mellitus: evidence of a positive association from a large prospective cohort study.

OBJECTIVE: Only a few prospective studies have examined the relationship between the frequency of cigarette smoking and the incidence of diabetes mellitus. The purpose of this study was to determine whether greater frequency of cigarette smoking accelerated the development of diabetes mellitus, and whether quitting reversed the effect. METHODS: Data were collected in the Cancer Prevention Study I, a prospective cohort study conducted from 1959 through 1972 by the American Cancer Society where volunteers recruited more than one million acquaintances in 25 US states. From these over one million original participants, 275,190 men and 434,637 women aged > or = 30 years were selected for the primary analysis using predetermined criteria. RESULTS: As smoking increased, the rate of diabetes increased for both men and women. Among those who smoked > or = 2 packs per day at baseline, men had a 45% higher diabetes rate than men who had never smoked; the comparable increase for women was 74%. Quitting smoking reduced the rate of diabetes to that of non-smokers after 5 years in women and after 10 years in men. CONCLUSIONS: A dose-response relationship seems likely between smoking and incidence of diabetes. Smokers who quit may derive substantial benefit from doing so. Confirmation of these observations is needed through additional epidemiological and biological research.

Vitamin supplement use and fatal non-Hodgkin's lymphoma among US men and women.

The authors evaluated the association between use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma in a large prospective mortality study of US men and women. During 14 years of follow-up (1982-1996), 1,571 non-Hodgkin's lymphoma deaths among 508,351 men and 1,398 non-Hodgkin's lymphoma deaths among 676,306 women were documented. Long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins was unrelated to fatal non-Hodgkin's lymphoma among either men or women. The multivariate relative risks for men who used supplements for 10 or more years were 1.03 (95% confidence interval (CI): 0.54, 2.00) for vitamin A supplements, 1.04 (95% CI: 0.78, 1.39) for vitamin C supplements, 1.06 (95% CI: 0.74, 1.51) for vitamin E supplements, and 1.14 (95% CI: 0.92, 1.40) for multivitamins. The multivariate relative risks for women who used supplements for 10 or more years were 1.40 (95% CI: 0.77, 2.54) for vitamin A supplements, 1.19 (95% CI: 0.89, 1.60) for vitamin C supplements, 1.27 (95% CI: 0.87, 1.84) for vitamin E supplements, and 1.21 (95% CI: 0.98, 1.50) for multivitamins. All associations became weaker when vitamin supplements were mutually adjusted. These findings do not support an important relation between long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma.

Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States.

Body weight and height have both been associated consistently with postmenopausal breast cancer but less consistently with prostate cancer. The present study examined the relationship between body mass index (BMI), height, and death from prostate cancer in two large American Cancer Society cohorts. Men in the study were selected from the male participants in Cancer Prevention Study I (CPS-I; enrolled in 1959 and followed through 1972) and Cancer Prevention Study II (CPS-II; enrolled in 1982 and followed through 1996). After exclusions, 1,590 prostate cancer deaths remained among 381,638 men in CPS-I and 3,622 deaths among 434,630 men in CPS-II. Cox proportional hazards modeling was used to compute rate ratios (RR) and to adjust for confounders. Prostate cancer mortality rates were significantly higher among obese (BMI, > or =30) than nonobese (BMI, <25) men in both cohorts [adjusted RR, 1.27; 95% confidence interval (CI), 1.04-1.56 in CPS-I; RR, 1.21; 95% CI, 1.07-1.37 in CPS-II]. Prostate cancer mortality rates in the CPS-I cohort were lowest for the shortest men (RR, 0.80; 95% CI, 0.63-1.03 for men <65 inches versus 65-66 inches) and highest for the tallest men (RR, 1.39; 95% CI, 1.11-1.74 for men > or =73 inches tall versus 65-66 inches). Rates remained constant among men 65-72 inches tall. No association between height and prostate cancer mortality was observed in the CPS-II cohort (RR, 1.03; 95% CI, 0.82-1.29 for men > or =75 versus 65-66 inches). These results support the hypothesis that obesity increases risk of prostate cancer mortality. Decreased survival among obese men may be a likely explanation for this association.

Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women.

CONTEXT: Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established. OBJECTIVES: To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. DESIGN AND SETTING: The American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996. PARTICIPANTS: A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. MAIN OUTCOME MEASURE: Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT). RESULTS: A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use >/=15 years ago, 1.31; 95% CI, 0.79-2.17). CONCLUSIONS: In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.