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Background: The American Cancer Society recommends physicians inform average risk women about endometrial cancer (EC) risk on reaching menopause, but new diagnoses are rising fastest in women <50 years. Educating these women about EC risks requires knowledge of risk factors. However, EC in young women is rare and challenging to study in single study populations., Methods: We included 13,846 incident EC patients (1,639 < 50 years) and 30,569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and EC risk. We created a risk score to evaluate the combined associations and population attributable fractions of these factors., Results: In younger and older women, we observed positive associations with BMI and diabetes, and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women ≥50 years (PHet<0.01). BMI was the strongest risk factor [OR≥35 vs <25 kg/m2=5.57 (95% CI:4.33-7.16) for <50 years; OR≥35 vs <25 kg/m2=4.68 (95% CI : 4.30-5.09) for ≥50 years; PHet=0.14]. Possessing ≥4 risk factors was associated with ∼9-fold increased risk in women <50 years and ∼4-fold increased risk in women ≥50 years (PHet<0.01). Together, 59.1% of ECs in women <50 and 55.6% in women ≥50 were attributable to these factors., Conclusions: Our data confirm younger and older women share common EC risk factors. Early educational efforts centered on these factors may help mitigate the rising EC burden in young women., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Adult obesity is a strong risk factor for endometrial cancer (EC); however, associations of early life obesity with EC are inconclusive. We evaluated associations of young adulthood (18-21 years) and adulthood (at enrolment) body mass index (BMI) and weight change with EC risk in the Epidemiology of Endometrial Cancer Consortium (E2C2)., Methods: We pooled data from nine case-control and 11 cohort studies in E2C2. We performed multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for BMI (kg/m2) in young adulthood and adulthood, with adjustment for BMI in adulthood and young adulthood, respectively. We evaluated categorical changes in weight (5-kg increments) and BMI from young adulthood to adulthood, and stratified analyses by histology, menopausal status, race and ethnicity, hormone replacement therapy (HRT) use and diabetes., Results: We included 14 859 cases and 40 859 controls. Obesity in adulthood (OR = 2.85, 95% CI = 2.47-3.29) and young adulthood (OR = 1.26, 95% CI = 1.06-1.50) were positively associated with EC risk. Weight gain and BMI gain were positively associated with EC; weight loss was inversely associated with EC. Young adulthood obesity was more strongly associated with EC among cases diagnosed with endometrioid histology, those who were pre/perimenopausal, non-Hispanic White and non-Hispanic Black, among never HRT users and non-diabetics., Conclusions: Young adulthood obesity is associated with EC risk, even after accounting for BMI in adulthood. Weight gain is also associated with EC risk, whereas weight loss is inversely associated. Achieving and maintaining a healthy weight over the life course is important for EC prevention efforts., (Published by Oxford University Press on behalf of the International Epidemiological Association 2023.)

Objective: Understanding how to identify the social determinants of health from electronic health records (EHRs) could provide important insights to understand health or disease outcomes. We developed a methodology to capture 2 rare and severe social determinants of health, homelessness and adverse childhood experiences (ACEs), from a large EHR repository., Materials and Methods: We first constructed lexicons to capture homelessness and ACE phenotypic profiles. We employed word2vec and lexical associations to mine homelessness-related words. Next, using relevance feedback, we refined the 2 profiles with iterative searches over 100 million notes from the Vanderbilt EHR. Seven assessors manually reviewed the top-ranked results of 2544 patient visits relevant for homelessness and 1000 patients relevant for ACE., Results: word2vec yielded better performance (area under the precision-recall curve [AUPRC] of 0.94) than lexical associations (AUPRC = 0.83) for extracting homelessness-related words. A comparative study of searches for the 2 phenotypes revealed a higher performance achieved for homelessness (AUPRC = 0.95) than ACE (AUPRC = 0.79). A temporal analysis of the homeless population showed that the majority experienced chronic homelessness. Most ACE patients suffered sexual (70%) and/or physical (50.6%) abuse, with the top-ranked abuser keywords being "father" (21.8%) and "mother" (15.4%). Top prevalent associated conditions for homeless patients were lack of housing (62.8%) and tobacco use disorder (61.5%), while for ACE patients it was mental disorders (36.6%-47.6%)., Conclusion: We provide an efficient solution for mining homelessness and ACE information from EHRs, which can facilitate large clinical and genetic studies of these social determinants of health., (© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure.

Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are ubiquitous man-made compounds that are possible hormonal disruptors. We examined whether exposure to these compounds may decrease fecundity in humans., Methods: Plasma levels of PFOS and PFOA were measured at weeks 4-14 of pregnancy among 1240 women from the Danish National Birth Cohort recruited from 1996 to 2002. For this pregnancy, women reported time to pregnancy (TTP) in five categories (<1, 1-2, 3-5, 6-12 and >12 months). Infertility was defined as having a TTP of >12 months or received infertility treatment to establish this pregnancy., Results: Longer TTP was associated with higher maternal levels of PFOA and PFOS (P < 0.001). Compared with women in the lowest exposure quartile, the adjusted odds of infertility increased by 70-134 and 60-154% among women in the higher three quartiles of PFOS and PFOA, respectively. Fecundity odds ratios (FORs) were also estimated using Cox discrete-time models. The adjusted FORs were virtually identical for women in the three highest exposure groups of PFOS (FOR = 0.70, 0.67 and 0.74, respectively) compared with the lowest quartile. A linear-like trend was observed for PFOA (FOR = 0.72, 0.73 and 0.60 for three highest quartiles versus lowest quartile). When all quartiles were included in a likelihood ratio test, the trends were significant for PFOS and PFOA (P = 0.002 and P < 0.001, respectively)., Conclusions: These findings suggest that PFOA and PFOS exposure at plasma levels seen in the general population may reduce fecundity; such exposure levels are common in developed countries.

Perfluorooctanoate and perfluorooctanesulfonate are used in many industrial products and have been widely detected in human blood. Both chemicals are associated with tumor development in animal studies, but data on carcinogenic potential in humans are sparse. We investigated the association between plasma levels of perfluorooctanoate and perfluorooctanesulfonate and cancer risk within a prospective Danish cohort of participants with no previous cancer diagnosis at enrollment. From enrollment, between December 1, 1993, and May 31, 1997, and through July 1, 2006, we identified 713 participants with prostate cancer, 332 with bladder cancer, 128 with pancreatic cancer, and 67 with liver cancer in the entire cohort and we selected a comparison subcohort of 772. Plasma concentrations of perfluorooctanoate and perfluorooctanesulfonate were measured in each participant by use of high-pressure liquid chromatography coupled to tandem mass spectrometry. We found no clear differences in incidence rate ratios for these cancers in relation to plasma concentrations of perfluorooctanoate or perfluorooctanesulfonate. A 30%-40% increase in risk estimates for prostate cancer was observed for the three upper quartiles of perfluorooctanesulfonate concentration compared with the lowest quartile (eg, for the lowest vs the fourth quartile, incidence rate ratio = 1.38, 95% confidence interval = 0.99 to 1.93). Plasma concentrations of perfluorooctanoate and perfluorooctanesulfonate in the general Danish population appear not to be associated with risk of prostate, bladder, pancreatic, or liver cancer.

False-positive results are inherent in the scientific process of testing hypotheses concerning the determinants of cancer and other human illnesses. Although much of what is known about the etiology of human cancers has arisen from well-conducted epidemiological studies, epidemiology has been increasingly criticized for producing findings that are often sensationalized in the media and fail to be upheld in subsequent studies. Herein we describe examples from cancer epidemiology of likely false-positive findings and discuss conditions under which such results may occur. We suggest general guidelines or principles, including the endorsement of editorial policies requiring the prominent listing of study caveats, which may help reduce the reporting of misleading results. Increased epistemological humility regarding findings in epidemiology would go a long way to diminishing the detrimental effects of false-positive results on the allocation of limited research resources, on the advancement of knowledge of the causes and prevention of cancer, and on the scientific reputation of epidemiology and would help to prevent oversimplified interpretations of results by the media and the public.

Epidemiologic evidence does not support a consistently increased cancer risk among women with cosmetic breast implants, but few studies have assessed risk beyond 15 years. Swedish women who underwent cosmetic breast implantation for the first time between January 1, 1965, and December 31, 1993 (N = 3486), were followed through December 31, 2002. Cancer incidence was ascertained through the nationwide Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to compare cancer incidence of women with implants with women in the general population. Mean follow-up among women with breast implants was 18.4 years (range = 0.1-37.8 years). The incidence of breast cancer was below expectation (SIR = 0.7, 95% CI = 0.6 to 1.0), whereas lung cancer was above expectation (SIR = 2.2, 95% CI = 1.3 to 3.4). With respect to cancer overall and all other specific cancer sites, including brain cancer and sarcoma, non-Hodgkin lymphoma, and multiple myeloma, no statistically significantly increased or decreased SIRs were observed. Stratification by duration of follow-up revealed no statistically significantly increased or decreased SIR, with the exception of a two- to threefold excess of lung cancer among women followed for more than 15 years, which would be expected due to the high prevalence of smoking among the Swedish women with implants in our study.

Background: Orthopedic implants and their fixatives contain materials with carcinogenic potential. Whether these implants are linked to subsequent cancer development remains unknown, mainly because large-scale, long-term follow-up data are scarce., Methods: We conducted a nationwide cohort study in Sweden to examine cancer incidence among 116,727 patients who underwent hip replacement surgery during the period from 1965 through 1994. Through record linkage to the Swedish Cancer Register, we identified all incident cancers through 1995 in this population (693,954 person-years of observation). For each cancer type, the observed number of cases was divided by that expected in the general Swedish population to produce standardized incidence ratios (SIRs)., Results: Relative to the general population, the cohort had no overall cancer excess (SIR = 1.01; 95% confidence interval [CI] = 0.99 to 1.03). However, we observed elevated SIRs for prostate cancer (SIR = 1.16; 95% CI = 1.11 to 1.22) and melanoma (SIR = 1.15; 95% CI = 1.01 to 1.30) and a reduction in stomach cancer risk (SIR = 0.83; 95% CI = 0.75 to 0.92). Long-term follow-up (>or=15 years) revealed an excess of multiple myeloma (SIR = 1.86; 95% CI = 1.01 to 3.11) and a statistically nonsignificant increase in bladder cancer (SIR = 1.42; 95% CI = 0.98 to 1.99). There was no material increase in risk for bone or connective tissue cancer for either men or women in any follow-up period., Conclusions: In this, the largest study to date, hip implant patients had similar rates of most types of cancer to those in the general population. Although the excesses of melanoma, multiple myeloma, and prostate and bladder cancers may be due to chance, confounding, or detection bias and should be interpreted cautiously, they warrant further investigation because of the ever-increasing use of hip implants at younger ages.

Background: The self-report of medical history and medication use is a common feature of epidemiological research., Methods: In a unique re-interview study, we evaluated the concordance of medical conditions and past medication use reported in two similar interviews 5 years apart., Results: In 196 re-interviews with the subjects themselves, and in 107 with next-of-kin of subjects who died after the first interview, agreement was good or excellent (kappa > or =0.40) for 90% (9/10) of the conditions asked about in the personal medical history for both next-of-kin and self-respondents. Agreement was excellent (kappa >0.75) for two conditions, high blood pressure and hysterectomy, among self-respondents. Self- and surrogate respondents also showed similar reproducibility for prescription medications, but next-of-kin respondents tended to have poor agreement (kappa <0.40) for over-the-counter (OTC) medications such as antacids, antihistamines, and analgesics. Next-of-kin also less reliably reported a family history of cancer. When analyses were stratified by type of surrogate respondent, concordance between the two interviews was generally higher for spouses than for other surrogate respondents., Conclusions: This research demonstrates that personal medical history and prescription medication use may be as reliably reported by next-of-kin as self-respondents, but suggests that additional information may be needed to validate measures of OTC medication use and family history of cancer for next-of-kin respondents, possibly through the review of hospital records.

The purpose of this review is to critically evaluate the collective epidemiologic evidence that a history of breast-feeding may decrease the risk of breast cancer. Original data for inclusion were identified through a MEDLINE(R) search of the English language literature from 1966 through 1998. To date, virtually all epidemiologic data regarding breast-feeding and breast cancer risk are derived from case-control studies, which vary according to classification of breast-feeding history. Overall, the evidence with respect to "ever" breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer. An inverse association between increasing cumulative duration of breast-feeding and breast cancer risk among parous women has been reported in some, but not all, studies; the failure to detect an association in some Western populations may be due to the low prevalence of prolonged breast-feeding. It appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women. It has been hypothesized that an apparently protective effect of breast-feeding may be due to elevated breast cancer risk among women who discontinue breast-feeding or who take medication to suppress lactation; however, the evidence is limited and should be interpreted with caution. The biology underlying a protective effect of breast-feeding and why this should be restricted to premenopausal women remain unknown, although several mechanisms have been postulated (hormonal changes, such as reduced estrogen; removal of estrogens through breast fluid; excretion of carcinogens from breast tissue through breast-feeding; physical changes in the mammary epithelial cells, reflecting maximal differentiation; and delay of the re-establishment of ovulation). While breast-feeding is a potentially modifiable behavior, the practical implication of reduced breast cancer risk among premenopausal women with prolonged durations of breast-feeding may be of marginal importance, particularly in Western societies.

The objective of this study was to evaluate and compare risk factor patterns in association with preeclampsia and gestational hypertension. The data were collected from The Swedish Medical Birth Register and include all nulliparas aged 34 years or less who gave birth at the University Hospital of Uppsala, Sweden, during 1987-1993. Of these 10,666 women, 4.4% developed gestational hypertension, and 5.2% developed preeclampsia. The following risk factors were significantly associated with increased risk of preeclampsia: type 1 diabetes (odds ratio = 5.58, 95% confidence interval 2.72-11.43), gestational diabetes (odds ratio = 3.11, 95% confidence interval 1.61-6.00), and twin birth (odds ratio = 4.17, 95% confidence interval 2.30-7.55). The positive associations between these variables and the risk of gestational hypertension were weaker and nonsignificant. Compared with underweight women (body mass index < 19.8), obese women (body mass index > 29) had increased risks of both gestational hypertension (odds ratio = 4.85, 95% confidence interval 1.97-11.92) and preeclampsia (odds ratio = 5.19, 95% confidence interval 2.35-11.48). Significantly lower risks of preeclampsia and gestational hypertension were observed for women born outside Nordic countries and in association with maternal smoking and summer birth. The similarities in risk factor patterns may indicate similarities in the biologic mechanisms underlying the two conditions.

Background: The established risk factors for female breast cancer, including nulliparity, age at first birth, age at menarche, and age at menopause, do not adequately explain the occurrence pattern of this cancer. Therefore, additional factors need to be considered to advance our understanding of the causes of breast cancer. Evidence obtained from animals and humans indicates that the perinatal period may be particularly important. Our earlier studies, based on a subsample of the present investigation, suggested that factors thought to be positively associated with estrogen levels during pregnancy are positively associated with breast cancer risk. However, the associated confidence intervals (CIs) were generally wide, indicating considerable variability in the data., Purpose: We studied a large number of incident breast cancer case patients and evaluated several perinatal variables in relation to breast cancer risk. These variables included some not previously studied, such as gestational age and neonatal jaundice. We also investigated twin membership as a predictor variable and death from breast cancer, in addition to occurrence of breast cancer, as an alternative outcome variable., Methods: Birth records for all deliveries at five different hospitals in Sweden during the period from 1874 through 1961 were used to define a large cohort of women. Incident case patients with breast cancer in this cohort were ascertained through the National Cancer Registry or the Uppsala Regional Cancer Registry from 1958 through 1994. In a case-control study nested in the cohort, we abstracted data from birth records on 1068 women with incident breast cancer and on 2727 control subjects individually matched to the case patients on date of birth. We modeled the data through conditional logistic regression. All P values were derived from two-sided statistical tests., Results: We found a markedly reduced risk for breast cancer in women whose mothers had pregnancy toxemia (odds ratio [OR] = 0.41; 95% CI = 0.22-0.79) and an excess risk on women who had neonatal jaundice (OR = 2.16; 95% CI = 1.27-3.67) or who were born before 33 weeks of gestation (OR = 3.96; 95% CI = 1.45-10.81). Compared with the risk for breast cancer in the singleton, the risk for breast cancer in dizygotic twins was increased, although this increase was not statistically significant (OR = 1.72; 95% CI = 0.92-3.20). There was no evidence in these data for a statistically significant or substantial association of breast cancer risk with birth size indicators (i.e., weight and length at birth and placental weight)., Conclusion and Implications: Because pregnancy toxemia is associated with low levels of estrogens and neonatal jaundice, severe prematurity, and dizygotic twins with high levels of estrogens, our findings suggest that estrogens and other hormonal factors, known to influence breast cancer risk in the adult, may also play a critical role during the intrauterine period.

To date, no study has attempted to correlate hormone levels between successive pregnancies in the same woman. Serum levels of total estradiol and total free estradiol have been measured between the eighth and the 17th weeks in the first and second full-term pregnancies of 34 white women participating in the Collaborative Perinatal Study, 1959-1965. Intraindividual interpregnancy Pearson's product moment correlations were calculated. Partial correlation coefficients (adjusted for gestational age) for log pregnancy total estradiol and total free estradiol were 0.78 and 0.73, respectively (p < 0.001). These findings provide evidence that levels of pregnancy estradiol are significantly and strongly correlated in successive pregnancies of the same woman. This phenomenon can provide an explanation for the higher concordance of breast cancer incidence between two sisters than between a mother and daughter in the familial pattern of breast cancer.

The authors studied the effect of averaging replicated assays of Factor IX coagulation activity and Factor IX antigen on each plasma specimen in improving the ability to detect carriers of hemophilia B. The improvement resulting from this procedure is particularly marked in tests depending on the linear regression of one characteristic on another to diagnose the carrier state. The effects of averaging assays on the ratio of Factor IX coagulation activity to Factor IX antigen were also explored. The benefits of averaging replications were not greatly increased by use of more than four replications.

Pharyngeal swabs were obtained from 832 children less than 14 years of age attending day-care centers and family day-care homes in central Massachusetts during a seven-week period beginning March 1, 1982. Colonization rates for Haemophilus influenzae and for H. influenzae type b were 60.7% and 15.1%, respectively. Nonwhite children were more likely to be carriers of non-b H. influenzae than white children (62.9% vs. 47.8%, p less than 0.025). Children in day care for more than six months were more likely to be carriers of non-b H. influenzae than children in day care for six months or less (52.9% vs. 45.5%, p less than 0.05). There was no association between colonization rates and age, sex, type of day-care setting, number of siblings, number sharing a bedroom, history of otitis media, or history of antibiotic use. The prevalence of ampicillin-resistant H. influenzae was 6.3% among all children and 10.3% among carriers of H. influenzae. The prevalence of ampicillin resistance was significantly higher among type b carriers than among carriers of other types (15.1% vs. 8.3%, p less than 0.05). Children who had taken ampicillin or amoxicillin within the past three months were much more likely to be colonized with ampicillin-resistant H. influenzae than were children who had not taken these antibiotics (13.5% vs. 4.8%, p less than 0.0005). These observations have important clinical implications for the management of children with H. influenzae disease.