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Background: Previous studies examining associations between use of fertility drugs and ovarian cancer risk have provided conflicting results. We used data from a large case-control study to determine whether fertility drug use significantly impacts ovarian cancer risk when taking into account parity, gravidity, and cause of infertility., Methods: Data from the Hormones and Ovarian Cancer Prediction (HOPE) study were used (902 cases, 1,802 controls). Medical and reproductive histories were collected via in-person interviews. Logistic regression was used to calculate ORs and 95% confidence intervals (CI). Models were adjusted for age, race, education, age at menarche, parity, oral contraceptive use, breastfeeding, talc use, tubal ligation, and family history of breast/ovarian cancer., Results: Ever use of fertility drugs was not significantly associated with ovarian cancer within the total HOPE population (OR, 0.93; 95% CI, 0.65-1.35) or among women who reported seeking medical attention for infertility (OR, 0.87; 95% CI, 0.54-1.40). We did observe a statistically significant increased risk of ovarian cancer for ever use of fertility drugs among women who, despite seeking medical attention for problems getting pregnant, remained nulligravid (OR, 3.13; 95% CI, 1.01-9.67)., Conclusions: These results provide further evidence that fertility drug use does not significantly contribute to ovarian cancer risk among the majority of women; however, women who despite infertility evaluation and fertility drug use remain nulligravid, may have an elevated risk for ovarian cancer., Impact: Our results suggest that fertility drug use does not significantly contribute to overall risk of ovarian cancer when adjusting for known confounding factors., (©2012 AACR.)

Objective: The objective of the study was to examine the association between lactation and maternal subclinical cardiovascular disease., Study Design: The Women and Infants Study of Healthy Hearts enrolled 607 mothers who delivered a singleton between 1997 and 2002. In 2007, participating mothers underwent measurements of carotid intima-media thickness, lumen diameter, adventitial diameter, and carotid-femoral pulse wave velocity. Multivariable linear and logistic regressions were used to estimate the associations between lactation and subclinical cardiovascular disease., Results: Compared with mothers who breastfed for 3 or more months after every birth, mothers who never breastfed exhibited a 0.13 mm larger lumen diameter (95% confidence interval, 0.04-0.22) and a 0.12 mm larger adventitial diameter (95% confidence interval, 0.02-0.22) in models adjusting for age, parity, birth outcome, sociodemographic variables, health-related behaviors, family history, gestational weight gain, early adult body mass index, current body mass index, C-reactive protein, blood pressure, cholesterol, triglyceride, high-density lipoprotein, glucose, and insulin levels., Conclusion: Mothers who do not breastfeed have vascular characteristics associated with a greater risk of cardiovascular disease., (Copyright © 2012 Mosby, Inc. All rights reserved.)

In considering the state of epidemiologic research, these are the "best" and the "worst" of times-the "best" from the perspective of scientific opportunities and the "worst" from the perspective of funding. In this commentary, the authors address this time of funding austerity from the points of view of individual researchers and research institutions. For researchers, the new tools of "-omics," large databases, communication by means of the World Wide Web, and global access offer ever-expanding scientific opportunities. The authors comment on research directions for which there is an enhanced likelihood of funding success: clinical and translational research, outcomes and effectiveness research, and global health research. The authors emphasize the need to be innovative and not bound by the conventional. For institutions, the authors suggest attention to innovation and impact, social networking, and finding the "right size" for training programs. Academic institutions also need to invest, supporting researchers and their ideas. Epidemiologists need to be true to their mission and prove that they can use innovation to advance health and welfare in a measurable way. Doing so will ensure that over the long term, epidemiologic research will remain a cornerstone for advancing population health.

Electronic health records in the United States currently isolate digital information in proprietary, institutional databases. Experts have identified inadequate data exchange as a leading challenge to advancements in care quality and efficiency. Recent federal health information technology incentives adopt an extensible standard, called the Continuity of Care Document (CCD), as a new basis for digital interoperability. Although this instrument was designed for individual provider communications, the CCD can be effectively reused for population-based research and public health. Three examples in this commentary demonstrate the potential of CCD aggregation and highlight required changes to existing public health and research practices. Transitioning to the use of this new interoperability standard should be a priority for public health investment, research, and development.

Innovation is the engine of scientific progress. Concern has been raised by the National Academies of Science about how well America is sustaining its "creative ecosystem." In this commentary, the author argues that we can all improve our ability to think innovatively through instruction and practice. The author presents a series of tools that are currently being taught in a curriculum developed at the University of Texas, based on earlier evidence-based creativity training programs. The tools are these: 1) finding the right question; 2) enhancing observation; 3) using analogies; 4) juggling induction and deduction; 5) changing your point of view; 6) broadening the perspective; 7) dissecting the problem; 8) leveraging serendipity and reversal; 9) reorganization and combination of ideas; 10) getting the most out of groups; and 11) breaking out of habitual expectations and frames. Each tool is explained using examples from science and public health. It is likely that each of us will identify with and agree with the usefulness of one or two of the tools described. Broader mastery of many of these tools, particularly when used in combination, has provided our students with a powerful device for enhancing innovation.

Background: Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer., Methods: Data from 13 ovarian cancer case-control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models., Findings: 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43-3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39-3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67-2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69-1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97-1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95-1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84-1·48, p=0·45)., Interpretation: Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer., Funding: Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

OBJECTIVE: To measure the relationships between soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and preeclampsia. STUDY DESIGN: We utilized a nested case-control study comprised of 211 preeclamptic women and 213 normotensive women with primiparous singleton pregnancies enrolled from ≥13 and <27 gestational weeks among the Danish National Birth Cohort of 100,000 women. Relationships between sFlt1, sEng and preeclampsia were estimated using smoothing splines in generalized linear models, adjusting for maternal age, body mass index, pre-existing hypertension, smoking, and gestational age. MAIN OUTCOME MEASURES: Preeclampsia was confirmed by an International Classification of Diseases (ICD) discharge diagnosis of 637.03, 637.04 637.09, 637.19 (ICD-8) or DO14 to DO15 (ICD-10) in the National Hospital Discharge Registry. In this sample, few cases delivered small for gestational age infants (8.1%) and the mean gestational age at delivery was term (38.2 ± 2.3 weeks). RESULTS: Doublings in the expressions of sFlt1 and sEng were associated with 39% (95% CI = 3%, 86%) and 74% (95% CI = 1%, 198%) increased risks of preeclampsia respectively. CONCLUSIONS: We conclude that second trimester high sFlt1 and sEng levels were possibly associated with an increased risk of preeclampsia after adjustment for maternal factors traditionally associated with the syndrome.

Purpose: We examine the impact of menopausal status, beyond menopausal symptoms, on health-related quality of life (HRQoL)., Methods: Seven hundred thirty-two women aged 40-65, regardless of health condition or menopausal status, were enrolled from single general internal medicine practice. Women completed annual questionnaires including HRQoL, and menopausal status and symptoms., Results: The physical health composite of the RAND-36 is lower in late peri (45.6, P < .05), early post (45.4, P < .05), and late postmenopausal women (44.6, P < .01), and those who report a hysterectomy (44.2, P < .01) compared to premenopausal women (47.1), with effect sizes of Cohen's d = .12-.23. The mental health composite of the RAND-36 is lower in late peri (44.7, P < .01), early post (44.9, P < .01), and late postmenopausal women (45.0, P < .05) and those who report a hysterectomy (44.2, P < .01) compared to premenopausal women (46.8), with effect sizes of Cohen's d = .15-.20. Findings are comparable adjusted for menopausal symptom frequency and bother., Conclusions: Over a 5-year follow-up period, we found a negative impact of menopause on some domains of HRQoL, regardless of menopausal symptoms. Clinicians should be aware of this relationship and work to improve HRQoL, rather than expect it to improve spontaneously when menopausal symptoms resolve.

Background: Toll-like receptors (TLRs) are involved in the innate immune response. We examined whether TLR variants are associated with Chlamydia trachomatis infection among women with pelvic inflammatory disease (PID)., Methods: We tested whether 18 tagging single nucleotide polymorphisms (tagSNPs) assayed in 4 TLR genes (TLR1, TLR2, TLR4, TLR6) and 2 adaptor molecules (TIRAP, MyD88) were associated with C. trachomatis among 205 African American women with clinically suspected PID from the PID Evaluation and Clinical Health Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). An empirical P value of <.004 was considered significant., Results: Women with PID who carried the TLR4 rs1927911 CC genotype had significantly increased odds of C. trachomatis (OR, 3.7; 95% CI, 1.6-8.8; P = .002). The TLR1 rs5743618TT genotype was also associated with C. trachomatis (OR, 2.8; 95% CI, 1.3-6.2; P = .008)., Conclusions: Among African American women with PID, variants in the TLR1 and TLR4 genes, which may increase signaling, were associated with increased C. trachomatis infection.

Objective: Sleep disturbance and hot flashes are common during menopause, but their association is not well understood. We sought to understand the associations among sleep disturbance and the frequency, bothersomeness, and interference of hot flashes in mid-life women., Study Design: STRIDE is a study of women ages 40-65 years at varied menopausal stages. We examined the cross-sectional associations of sleep disturbance with the frequency and bothersomeness of hot flashes, and interference of hot flashes with work, social, and leisure activities during the 2nd year of STRIDE., Main Outcome Measure: Self-reported sleep disturbance., Results: Of the 623 women with complete data, 370 (59%) reported having hot flashes. Bivariate analyses showed that reporting hot flashes with bother, but not hot flashes alone, was associated with sleep disturbance (odds ratio [OR] [95% confidence interval (CI)]: 2.8 [2.0-4.0] and 1.3 [0.7-2.5], respectively). In multivariable models, women reporting bothersome hot flashes were more likely to report sleep disturbance (OR [95% CI]: 2.1 [1.4-3.2]) compared to women who reported no hot flashes. When the perceived interference of hot flashes with work, social activities, and leisure activities were included in the model, the relationships between bothersome hot flashes and sleep disturbance disappeared., Conclusions: Hot flashes are not associated with sleep disturbance, unless they are bothersome. Mid-life patients should routinely be queried about the bothersomeness of their hot flashes., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The National Academies of Science recently criticized the state of scientific innovation and competitiveness in the United States. Evaluations of already-established creativity training programs--examining a broad array of students, from school age to adult and with a wide range of abilities--have shown that such courses improve thinking skills, attitudes, and performance. Although academic medicine provides informal training in creativity and innovation, it has yet to incorporate formal instruction on these topics into medical education. A number of existing, thoughtfully constructed and evaluated creativity programs in other fields provide a pedagogical basis for developing creativity training programs for the health sciences. The content of creativity training programs typically includes instruction and application in (1) divergent thinking, (2) problem solving, and (3) creative production. Instructional formats that have been shown to elicit the best outcomes are an admixture of lectures, discussion, and guided practice. A pilot program to teach innovative thinking to health science students at the University of Texas includes instruction in recognizing and finding alternatives to frames or habitual cognitive patterns, in addition to the constructs already mentioned. As innovation is the engine of scientific progress, the author, founder of Innovative Thinking, the creativity training pilot program at the University of Texas, argues in this commentary that academic health centers should implement and evaluate new methods for enhancing science students' innovative thinking to keep the United States as a worldwide leader in scientific discovery.

PEACH trial data were used to evaluate the relationship between subsequent sexually transmitted infection and recurrent pelvic inflammatory disease on infertility and chronic pelvic pain (CPP). Recurrent pelvic inflammatory disease was associated with an almost 2-fold increase in infertility and more than 4-fold increase in CPP. Subsequent sexually transmitted infection was associated with CPP, but not infertility.

Purpose: An assay for the single-nucleotide polymorphism (SNP), rs61764370, has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'-UTR miRNA binding site of the KRAS oncogene and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published article, analyzing fewer than 1,000 subjects in total, has examined this association., Experimental Design: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from 19 studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival (PFS) data and 18 studies with all-cause mortality data., Results: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% CI: 0.95-1.10), serous EOC (OR = 1.08, 95% CI: 0.98-1.18), familial EOC (OR = 1.09, 95% CI: 0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR = 1.09, 95% CI: 0.88-1.36). There was little evidence for association with survival time among unselected cases (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS in 540 cases treated with carboplatin and paclitaxel (HR = 1.18, 95% CI: 0.93-1.52)., Conclusions: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction, therefore, seems unwarranted., (©2011 AACR.)

The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of ovarian cancer. We found no association between variation in IGF1, IGFBP1 or IGFBP3 and risk of invasive disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at P<0.05 and followed-up one of the associated SNPs. We conducted genotyping in 3216 additional non-Hispanic white cases and 5382 additional controls and were able to independently replicate our initial findings. In the combined set of studies, rs4320932 was associated with a 13% decreased risk of ovarian cancer per copy of the minor allele carried (95% confidence interval 0.81-0.93, P-trend=7.4 × 10(-5)). No heterogeneity of effect across study centers was observed (p(het)=0.25). IGF2 is emerging as an important gene for ovarian cancer; additional genotyping is warranted to further confirm these associations with IGF2 and to narrow down the region harboring the causal SNP.

Background: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.1-1.5, P(trend) = 0.003)., Methods: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium., Results: No evidence for an association with all cancers or serous cancers was observed in a combined analysis of data from the replication studies (all: OR = 1.0, 95% CI = 0.9-1.1, P(trend) = 0.61; serous: OR = 1.0, 95% CI = 0.9-1.1, P(trend) = 0.85) or from the combined analysis of discovery and replication studies (all: OR = 1.0, 95% CI = 1.0-1.1, P(trend) = 0.28; serous: OR = 1.1, 95% CI = 1.0-1.2, P(trend) = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies., Conclusions: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study., Impact: Our findings, based on a larger sample size, emphasize the importance of replicating potentially promising genetic risk associations., (©2011 AACR.)

Objective: We studied the microbial correlates of time to care and long-term outcomes among pelvic inflammatory disease (PID) patients, as delayed care may increase the risk for reproductive sequelae., Methods: Mean days of pain before care were compared by microbial pathogen (Chlamydia trachomatis only, Neisseria gonorrhoeae only, Mycoplasma genitalium only, coinfection with 2 or more pathogens, or no pathogens) among 298 women with histologically confirmed endometritis from the PID Evaluation and Clinical Health study. Times to pregnancy and recurrent PID were assessed over a mean of 84 months and compared between women who delayed care (≥14 days) and women who sought early care, in the entire cohort and in subsets defined by microbial infection. Analyses were adjusted for age and race, additionally time to pregnancy was adjusted for self-reported baseline infertility., Results: Patients waited a mean of 7 days before seeking care for symptoms. Time to care was longest among women infected by C. trachomatis only (12.3 ± 9.4 days) and M. genitalium only (10.9 ± 8.9 days) and the shortest among women infected by N. gonorrhoeae only (4.6 ± 5 days) or coinfection (5.6 ± 5.1 days, P < 0.001). Rates of infertility, recurrent PID, and chronic pelvic pain were frequent overall (17%, 20%, and 36%) and tended to be higher, albeit nonsignificantly, after delayed care., Conclusions: Among women with clinically suspected PID, time to care was generally high. C. trachomatis and M. genitalium positive women had the longest times to care. Although reproductive morbidity was high in this cohort, associations with delayed care were nonsignificant.

Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcell-mediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs7650365, were associated with increased risk of serous ovarian cancer [HetOR = 1.42 (1.15-1.74) and the HomOR = 1.63 (1.10-1.42), p-trend = 0.0002] and [HetOR = 0.97 (0.80-1.17), HomOR = 0.74 (0.58-0.93), p-trend = 0.009], respectively. We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer., (Copyright © 2010 UICC.)

Objective: To evaluate the obstetrical outcome measures of birth weight (BW) and length of gestation (GA) in singleton pregnancies from in vitro fertilization (IVF), donor egg (DE), and gestational carrier (GC) cycles., Design: Retrospective data analysis., Setting: Clinics., Patient(s): SART data set from the years 2004-2006., Intervention(s): The BW and GA of singleton pregnancies were compared in IVF, DE, and GA cycles., Main Outcome Measure(s): The BW and GA data were compared to evaluate the effects on these outcomes of the source of the egg, the uterus, or sperm or the primary reason given for treatment., Result(s): The mean BW and GA for DE cycles were 3,236 g and 37.4 weeks, respectively, which were less than those of IVF [3,265 g and 37.7 weeks]. GC BW was greater at 3,309 g with GA of 37.2 weeks. No difference was seen between donor or spouse sperm source; however, most female fertility-diagnosis cycles were associated with lower BW and GA than male factor-related cycles., Conclusion(s): Reduced BW and GA were observed for DE cycles versus IVF or GC cycles, suggesting that the uterine environment was more important to these outcomes than egg quality. Whereas altering the sperm source had no effect, female infertility diagnoses were associated with reductions in BW and GA., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Data in epidemiological studies sometimes are collected off-schedule from planned study visits. In an ancillary study to the Study of Women's Health Across the Nation (SWAN), longitudinal breast density data were collected retrospectively from mammograms that were not acquired at the study visits. We propose a method to estimate the off-schedule breast density measurements at the time of study visits., Methods: This method uses local linear interpolation, with multiply imputed error terms drawn from assumed subject-specific normal distributions based on the within-subject standard deviations of mammographic density measurements. We evaluate the validity and implications of this approach., Results: Coefficients of random intercept models used to assess the association between annual changes in body mass index and dense breast area estimated with this approach (β = -0.17, p = .46) differed from those obtained when each mammogram was matched to the nearest study visit (β = -0.30, p = .04). The proposed estimation approach had a small average prediction error (0.11 cm2)., Conclusions: Because matching does not incorporate breast density changes over time, our local linear interpolation with multiple imputation approach may provide more accurate results. The proposed approach is applicable to other epidemiologic studies with off-schedule data in which the missing variable changes linearly over relatively short periods of time., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Few studies have examined methods of contraception, beyond oral contraceptives (OCs) and tubal ligation, in relation to ovarian cancer risk., Methods: Nine hundred two cases with incident ovarian/peritoneal/tubal cancer were compared with 1800 population-based control subjects. Women self-reported all methods of contraception by using life calendars., Results: Each of the contraceptive methods examined reduced the risk of ovarian cancer as compared with use of no artificial contraception. Comparing ever versus never use, after adjustment for potentially confounding factors and all other methods of contraception, the methods of contraception that emerged as protective were OCs (adjusted odds ratio [adj OR] 0.75, 95% confidence interval [CI] 0.61-0.93); tubal ligation (adj OR 0.63, 95% CI 0.51-0.77); intrauterine devices (IUDs) (adj OR 0.75, 95% CI 0.59-0.95); and vasectomy (adj OR 0.77, 95% CI 0.61-0.99). Although for OCs and tubal ligation we found that the longer the duration of use, the greater the effect, for IUDs the pattern was reversed: significant protection occurred with short duration and progressively greater risk (albeit nonsignificant) was seen with longer duration of use., Conclusions: In the largest case-control study to date, a range of effective methods of contraception reduced the risk for ovarian cancer. OCs and tubal ligation reduced ovarian cancer risk with lower odds ratios with longer duration of use, whereas IUDs reduced risk overall, having the greatest impact with short duration of use., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To estimate whether women who deliver small babies due to preterm birth or growth restriction have excess risk for cardiovascular disease and diabetes later in life., Methods: Eight years after pregnancy, we estimated the prevalence of metabolic syndrome and its components in a cohort study of women with prior preterm (preterm birth before 37 weeks, n=181) or small for gestational age ([SGA], less than the tenth percentile, n=192) births, compared with women with term births (37 or more weeks, n=306). Women delivered at Magee-Womens Hospital in Pittsburgh, Pennsylvania, and those with preeclampsia or prepregnancy diabetes or hypertension were excluded. Women underwent a structured interview and fasting blood sampling., Results: Women were, on average, 8 years postpartum and 39 years old at evaluation. Women with a prior preterm birth had higher blood pressure, triglycerides, and LDL-cholesterol compared with those in a term control group. Women with prior SGA births were leaner and more likely to smoke compared with those with term births. Women with prior preterm birth had elevated risk of metabolic syndrome, adjusted for demographic, smoking and body size factors (23% preterm compared with 17% control group; odds ratio [OR] 1.76 [1.06, 2.80]). In women with a prior preterm birth, low HDL (11% preterm compared with 5% control group; OR 2.6 [1.2, 5.2]), hypertriglyceridemia (22% compared with 14%; OR 1.9 [1.2, 2.9]), and elevated glucose (24% compared with 19%; OR 1.5 [1.0, 2.3]) accounted for this excess metabolic syndrome. In women with SGA, the only element of metabolic syndrome that was aberrant was glucose metabolism., Conclusion: Eight years after pregnancy, women with prior preterm or SGA births had evidence of metabolic syndrome compared with women with term births. Screening and intervention in these women after pregnancy may delay or prevent disease., Level of Evidence: : II.

Chlamydia trachomatis polymorphic membrane proteins (Pmps) may increase genital tract inflammation and play a role in virulence. Antibody levels for PmpA, PmpD, and PmpI, measured in densitometric units, were assessed among a pilot sample of 40 C. trachomatis-infected women with mild-to-moderate clinical PID. Women who expressed antibodies to PmpA were less likely to achieve pregnancy (40.0% versus 85.7%; P = 0.042) and less likely to have a live birth (0.0% versus 80.0%; P = 0.005) compared to women who did not express antibody to PmpA. Women who expressed antibodies to PmpI were more likely to have upper genital tract infection (61.5% versus 20.0%; P = 0.026). However, seropositivity to PmpI and PmpD did not modify the risk of reproductive sequelae or inflammation. Seropositivity to chlamydial PmpA may represent a biomarker of increased risk of sequelae secondary to infection with C. trachomatis., (Copyright © 2011 Brandie D. Taylor et al.)

Interoperability is a requirement of recent electronic health record (EHR) adoption incentive programs in the United States. One approved structure for clinical data exchange is the continuity of care document (CCD). While primarily designed to promote communication between providers during care transitions, coded data in the CCD can be re-used to aggregate data from different EHRs. This provides an opportunity for provider networks to measure quality and improve population health from a consolidated database. To evaluate such potential, this research collected CCDs from 14 organizations and developed a computer program to parse and aggregate them. In total, 139 CCDs were parsed yielding 680 data in the core content modules of problems, medications, allergies and results. Challenges to interoperability were catalogued and potential quality metrics evaluated based on available content. This research highlights the promise of CCDs for population health and recommends changes for future interoperability standards.

Sodium consumption is a target for prevention of cardiovascular disease (CVD). The relationship between sodium intake and blood pressure (BP) is well-established, but the relationship with CVD is less clear. This review focuses on studies investigating the association between sodium intake and CVD within five principal subgroups: age, underlying BP, gender, body size, and ethnicity. We conclude that sodium reduction results in decreased CVD risk in the general population, and some susceptible subgroups may especially benefit from preventive efforts. Older individuals, those with underlying elevated BP, and those with increased body size may benefit most, but men and women of all ages, ethnicities, and normotensives also experience reduced CVD risk in relation to lowered sodium intake. Public health policy to reduce sodium intake in the United States would have significant cost-savings, far greater than the cost of intervention, and would also result in a significant gain in quality-adjusted life years.

Objective: To investigate the association between self-reported endometriosis and the putative functional promoter +331C/T single nucleotide polymorphism and the PROGINS allele., Design: Control subjects from ovarian cancer case-control studies participating in the international Ovarian Cancer Association Consortium. The majority of controls are drawn from population-based studies., Setting: An international ovarian cancer consortium including studies from Australia, Europe, and the United States., Patient(s): Five thousand eight hundred twelve white female controls, of whom 348 had endometriosis, from eight ovarian cancer case-control studies., Intervention(s): None., Main Outcome Measure(s): Genotypes for the +331C/T single nucleotide polymorphism and PROGINS allele and a history of endometriosis., Result(s): The occurrence of endometriosis was reduced in women carrying one or more copies of the +331 T allele (odds ratio=0.65; 95% confidence interval: 0.43-0.98), whereas there was no association between the PROGINS allele and endometriosis (odds ratio=0.94, 95% confidence interval 0.76-1.16)., Conclusion(s): Additional studies of the +331C/T variant are warranted given the current finding and the equivocal results of previous studies. The +331 T allele has been shown to result in a reduced progesterone (P) receptor A to P receptor B ratio, and if the observed association with endometriosis is confirmed it would suggest that this ratio is important for this disease., (Copyright © 2011. Published by Elsevier Inc.)

The last century of innovative public health discoveries has led most of the world's population to lead longer, healthier lives. Yet, the future holds some of the greatest public health challenges in mankind's history. Global disparities in health; medication safety; climate change; epidemics of obesity and diabetes; an aging world demographic; and emerging infections all represent problems requiring scientific solutions. The solutions to these problems, like the solutions to those in the last century that contributed so greatly to our quality of life, will require paradigm-shifting innovation. To maximize individual innovative potential, one strategy is formal instruction in the methods of innovative thinking. Teaching innovative thinking is rarely integrated into science training. However 40 years of accumulated evidence suggests that formal instruction results in improved thinking skills. I describe here some of the methods integrated into a course for graduate and professional health science students entitled Innovative Thinking. The curriculum consists of three components: recognizing and finding alternatives to habitual cognitive patterns; learning to use tools that enhance idea generation and originality; and harmonizing divergent thinking with the process of convergent thinking that is central to the scientific method. To build more innovative environments, institutions can promote team science, fund staged scientific designs that are heavy on early prototypes, reward and grow the training programs of past innovators, and become less risk averse. Although public health has accomplished much, it must continue to battle major, growing causes of disease and disability. Innovation is the engine of scientific discovery. Releasing the great potential for discovery in all of us must be central to forwarding health and prosperity in the world., (© BioMed Central London 2011.)

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10⁻⁴ and P = 6 × 10⁻⁴, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10⁻⁹ and P = 4 × 10⁻¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

As former chairs of 3 of the largest departments of epidemiology in the country, the authors provide "lessons learned" on how to be an epidemiology chair. To start, they suggest discussing strategic visioning with faculty, staff, and students; evaluating existing operational and governance structures; setting a predictable style; and considering which traditions to keep and which to modernize. Next, the authors consider key administrative issues. Recruitment and retention of the best faculty and students are critical to a successful department's future. A great department requires a great vision. To manage the change a new vision creates, the chair must attain buy-in and proceed with persistence. Chairs must promote the interests of the department to higher administration, a job best accomplished by being a team player and picking your battles. Keeping an eye on the mission involves balancing quality education with research and always striving to improve public health. Finally, a chair must continuously assess whether he or she is doing the best job. Eventually, the chair must know when to quit and how to quit well. Although being chair is demanding and sometimes difficult, it is a position that can be rewarding to both the individual and the department.

Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ≤ 10⁻⁴) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P ≤ 5 × 10⁻⁸ (8q24, P = 8.0 × 10⁻¹⁵ and 2q31, P = 3.8 × 10⁻¹⁴) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10⁻⁸ and 17q21, P = 1.4 × 10⁻⁷). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.

Privacy seems to be of increasing public concern, as evidenced by the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, a regulatory framework that appears to hinder access to data and thus to limit population-based research. A 2009 Institute of Medicine (IOM) report urged Congress, via the US Department of Health and Human Services (HHS), to develop a new approach to protecting privacy that would not employ the HIPAA Privacy Rule. In an accompanying article in the Journal, Nattinger et al. (Am J Epidemiol. 2010;172(6):637-644) employ one of the constructs recommended in the IOM report: use of a centralized honest broker. Unfortunately, Nattinger et al.'s approach would not be acceptable to all institutional review boards. The IOM report also urged the HHS to reduce variability in interpretations of the HIPAA Privacy Rule by privacy boards through revised and expanded guidance and harmonization. HHS Secretary Kathleen Sebalius has not acted upon any of the IOM report recommendations. The need to remove major barriers to human health research cannot be forgotten. At risk is America's progress in finding solutions to our most pressing health concerns.

Context: Preterm birth is associated with maternal cardiovascular risk, but mechanisms are unknown., Objective: We considered that dyslipidemia may predispose women to both conditions and that prepregnancy lipids may be related to preterm birth risk. We hypothesized that low or high prepregnancy plasma lipids would be associated with preterm birth., Design, Setting, and Participants: A total of 1010 women (49% black) enrolled in the multicenter, prospective Coronary Artery Risk Development in Young Adults study with at least one singleton birth during 20 yr of follow-up were evaluated., Main Outcome Measure: Postbaseline preterm births less than 34 wk or 34 to less than 37 wk vs. greater than 37 wk gestation., Results: We detected a U-shaped relationship between prepregnancy cholesterol concentrations and preterm birth risk. Women with prepregnancy cholesterol in the lowest quartile compared with the second quartile (<156 vs. 156-171 mg/dl) had an increased risk for preterm birth 34 to less than 37 wk (odds ratio 1.86; 95% confidence interval 1.10, 3.15) and less than 34 wk (odds ratio 3.04; 1.35, 6.81) independent of race, age, parity, body mass index, hypertension during pregnancy, physical activity, and years from measurement to birth. Prepregnancy cholesterol in the highest quartile (>195 mg/dl) was also associated with preterm birth less than 34 wk among women with normotensive pregnancies (odds ratio 3.80; 95% confidence interval 1.07, 7.57). There were no associations between prepregnancy triglycerides, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol and preterm birth., Conclusions: Both low and high prepregnancy cholesterol were related to preterm birth risk. These may represent distinct pathways to the heterogeneous outcome of preterm birth. Additional studies are needed to elucidate mechanisms that link low or high cholesterol to preterm birth and later-life sequelae.

Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type., Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site., Results: The five polymorphisms were not associated with ovarian carcinoma overall (P(trend) > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P(heterogeneity) = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05)., Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification., Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.

Chlamydia trachomatis infection, the most common reportable disease in the United States, can lead to pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain. Although C. trachomatis is identified among many women who receive a diagnosis of PID, the incidence and timing of PID and long-term sequelae from an untreated chlamydial infection have not been fully determined. This article examines evidence reviewed as part of the Centers for Disease Control and Prevention Chlamydia Immunology and Control Expert Advisory Meeting; 24 reports were included. We found no prospective studies directly assessing risk of long-term reproductive sequelae, such as infertility, after untreated C. trachomatis infection. Several studies assessed PID diagnosis after untreated chlamydial infection, but rates varied widely, making it difficult to determine an overall estimate. In high-risk settings, 2%-5% of untreated women developed PID within the approximately 2-week period between testing positive for C. trachomatis and returning for treatment. However, the rate of PID progression in the general, asymptomatic population followed up for longer periods appeared to be low. According to the largest studies, after symptomatic PID of any cause has occurred, up to 18% of women may develop infertility. In several studies, repeated chlamydial infection was associated with PID and other reproductive sequelae, although it was difficult to determine whether the risk per infection increased with each recurrent episode. The present review critically evaluates this body of literature and suggests future research directions. Specifically, prospective studies assessing rates of symptomatic PID, subclinical tubal damage, and long-term reproductive sequelae after C. trachomatis infection; better tools to measure PID and tubal damage; and studies on the natural history of repeated chlamydial infections are needed.

Childhood obesity is a serious public health problem resulting from energy imbalance (when the intake of energy is greater than the amount of energy expended through physical activity). Numerous health authorities have identified policy interventions as promising strategies for creating population-wide improvements in physical activity. This case study focuses on energy expenditure through physical activity (with a particular emphasis on school-based physical education [PE]). Policy-relevant evidence for promoting physical activity in youth may take numerous forms, including epidemiologic data and other supporting evidence (e.g., qualitative data). The implementation and evaluation of school PE interventions leads to a set of lessons related to epidemiology and evidence-based policy. These include the need to: (i) enhance the focus on external validity, (ii) develop more policy-relevant evidence on the basis of "natural experiments," (iii) understand that policy making is political, (iv) better articulate the factors that influence policy dissemination, (v) understand the real-world constraints when implementing policy in school environments, and (vi) build transdisciplinary teams for policy progress. The issues described in this case study provide leverage points for practitioners, policy makers, and researchers as they seek to translate epidemiology to policy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on enhancing use and quality of colorectal cancer screening., Participants: A non-DHHS, nonadvocate 13-member panel representing the fields of cancer surveillance, health services research, community-based research, informed decision-making, access to care, health care policy, health communication, health economics, health disparities, epidemiology, statistics, thoracic radiology, internal medicine, gastroenterology, public health, end-of-life care, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience., Evidence: Presentations by experts and a systematic review of the literature prepared by the RTI International-University of North Carolina Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience., Conference Process: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government., Conclusions: The panel found that despite substantial progress toward higher colorectal cancer screening rates nationally, screening rates fall short of desirable levels. Targeted initiatives to improve screening rates and reduce disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. This could be achieved by utilizing the full range of screening options and evidence-based interventions for increasing screening rates. With additional investments in quality monitoring, Americans could be assured that all screening achieves high rates of cancer prevention and early detection. To close the gap in screening, this report identifies the following priority areas for implementation and research to enhance the use and quality of colorectal cancer screening: • Eliminate financial barriers to colorectal cancer screening and appropriate follow up. • Widely implement interventions that have proven effective at increasing colorectal cancer screening, including patient reminder systems and one-on-one interactions with providers, educators, or navigators. • Conduct research to assess the effectiveness of tailoring programs to match the characteristics and preferences of target population groups to increase colorectal cancer screening. • Implement systems to ensure appropriate follow-up of positive colorectal cancer screening results. • Develop systems to assure high quality of colorectal cancer screening programs. • Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings.

Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model was fit, the results were unchanged. Test for heterogeneity of the odds ratios revealed consistency across the 14 replication sites but significant differences compared with the original study population (P = 0.03). This study underscores the need for replication of putative findings in genetic association studies.

Objective: Mycoplasma genitalium has been identified as a cause of pelvic inflammatory disease (PID), a clinical syndrome associated with inflammation of the female upper genital tract and serious reproductive sequelae. As the demographic, behavioural and sexual risk profile of women with M genitalium-associated PID is not well understood, the characteristics of M genitalium-infected women presenting with clinically suspected PID were investigated., Methods: Data from 586 participants in the PID Evaluation and Clinical Health Study were analysed. Demographic, sexual history and behavioural characteristics, including age, race, marital status, education level, sexual activity, number of sexual partners, history of sexually transmitted infection (STI), bacterial vaginosis and PID, contraception use, oral and anal sex, age at sexual debut, douching practices and drug, alcohol and tobacco use, were compared between 88 women testing positive and 498 women testing negative for M genitalium by PCR in the cervix and/or endometrium. Twenty-two women with M genitalium mono-infections were compared with 172 women who tested positive for Neisseria gonorrhoeae by culture and/or Chlamydia trachomatis by PCR., Results: Age under 25 years, douching two or more times per month and smoking were independently associated with M genitalium. Women with M genitalium mono-infections were significantly less likely to be African-American (59.1% vs 86.0%, p = 0.001) than women with N gonorrhoeae and/or C trachomatis., Conclusions: Women infected with M genitalium had some characteristics commonly associated with PID and other STI. The demographic, sexual and behavioural characteristics of M genitalium-positive women were similar to women with chlamydial and/or gonococcal PID.

Objective: As the consequences of Mycoplasma genitalium in pregnant women are unknown, we examined the relationship between prenatal M. genitalium infection and SAB., Methods: The presence of M. genitalium was determined by PCR in urine from 82 women who subsequently experienced a SAB and 134 women who maintained their pregnancies past 22 weeks gestation. The relationships between M. genitalium and subsequent SAB, demographic, current pregnancy, and reproductive health history characteristics were evaluated., Results: Compared to women without M. genitalium, women with M. genitalium were more likely to report nulliparity (41.7% versus 17.4%, P = .04), history of pelvic inflammatory disease (27.3% versus 8.8%, P = .08), prior C. trachomatis infection (63.6% versus 36.9%, P = .11,) and problems getting pregnant (18.2% versus 4.4%, P = .10). M. genitalium was not associated with SAB (AOR 0.9, 95% CI 0.2-3.8)., Conclusions: Pregnant women who test positive for M. genitalium do not have an increased risk of SAB but report a history of reproductive morbidities.

We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope 1 (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95% CI, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer.

In this article, the authors discuss current challenges and opportunities in epidemiology that will affect the field's future. Epidemiology is commonly considered the methodologic backbone for the fields of public health and outcomes research because its practitioners describe patterns of disease occurrence, identify risk factors and etiologic determinants, and demonstrate the usefulness of interventions. Like most aspects of science, epidemiology is in rapid flux. Several factors that are influencing and will continue to influence epidemiology and the health of the public include factors fundamental to framing the discipline of epidemiology (i.e., its means of communication, its methodologies, its access to data, its values, its population perspective), factors relating to scientific advances (e.g., genomics, comparative effectiveness in therapeutics), and factors shaping human health (e.g., increasing globalism, the environment, disease and lifestyle, demographics, infectious disease).

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).

Genomic analysis of the Chlamydiaceae has revealed a multigene family encoding large, putatively autotransported polymorphic membrane proteins (Pmps) with nine members in the sexually transmitted pathogen Chlamydia trachomatis. While various pathogenesis-related functions are emerging for the Pmps, observed genotypic and phenotypic variation among several chlamydial Pmps in various Chlamydia species has led us to hypothesize that the pmp gene repertoire is the basis of a previously undetected mechanism of antigenic variation. To test this hypothesis, we chose to examine the serologic response of C. trachomatis-infected patients to each Pmp subtype. Immune serum samples were collected from four populations of patients with confirmed C. trachomatis genital infection: 40 women with pelvic inflammatory disease from Pittsburgh, PA; 27 and 34 adolescent/young females from Oakland, CA, and Little Rock, AR, respectively; and 58 adult male patients from Baltimore, MD. The Pmp-specific antibody response was obtained using immunoblot analysis against each of the nine recombinantly expressed Pmps and quantified by densitometry. Our results show that nearly all C. trachomatis-infected patients mount a strong serologic response against individual or multiple Pmp subtypes and that the antibody specificity profile varies between patients. Moreover, our analysis reveals differences in the strengths and specificities of the Pmp subtype-specific antibody reactivity relating to gender and clinical outcome. Overall, our results indicate that the Pmps elicit various serologic responses in C. trachomatis-infected patients and are consistent with the pmp gene family being the basis of a mechanism of antigenic variation.

Objectives: As the aetiology of bacterial vaginosis (BV) is not well understood, this study sought to determine the relationships between several fastidious microbes, BV and selected clinical characteristics of BV., Methods: Endometrial and cervical specimens from 50 women with non-gonococcal, non-chlamydial endometritis were tested for Leptotrichia sanguinegens/amnionii, Atopobium vaginae, bacterial vaginosis-associated bacteria 1 (BVAB1), Ureaplasma urealyticum biovar 2 (UU-2) and Ureaplasma parvum using PCR. BV was categorised using Nugent's and Amsel's criteria. Odds ratios (OR) adjusted for age and race were estimated using multivariable logistic regression., Results: Although elevated pH was a universal feature, other BV characteristics differed by pathogen, suggesting variable clinical presentation. Only UU-2 was strongly associated with vaginal discharge, but a positive whiff test and a 20% or greater classification of epithelial cells as clue cells were more common among women with L sanguinegens/amnionii, A vaginae and BVAB1. For each of these bacteria, there were trends towards associations with BV defined by Amsel's criteria (L sanguinegens/amnionii OR 2.9, 95% CI 0.5 to 15.7; A vaginae OR 2.6, 95% CI 0.6 to 11.4; BVAB1 OR 5.7, 95% CI 1.0 to 31.1) and significant associations with BV defined by Gram stain (L sanguinegens/amnionii OR 17.7, 95% CI 2.8 to 113.0; A vaginae OR 19.2, 95% CI 3.7 to 98.7; BVAB1 OR 21.1, 95% CI 2.2 to 198.5)., Conclusions: L sanguinegens/amnionii, A vaginae and BVAB1 are associated with clinical characteristics consistent with BV and BV defined by Nugent's and Amsel's criteria. These fastidious bacteria may cause unrecognised infection, as none was associated with abnormal vaginal discharge.

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

Objective: To examine dose-response relationships between the cumulative number of months women lactated and postmenopausal risk factors for cardiovascular disease., Methods: We examined data from 139,681 postmenopausal women (median age 63 years) who reported at least one live birth on enrolling in the Women's Health Initiative observational study or controlled trials. Multivariable models were used to control for sociodemographic (age, parity, race, education, income, age at menopause), lifestyle, and family history variables when examining the effect of duration of lactation on risk factors for cardiovascular disease, including obesity (body mass index [BMI] at or above 30), hypertension, self-reported diabetes, hyperlipidemia, and prevalent and incident cardiovascular disease., Results: Dose-response relationships were seen; in fully adjusted models, women who reported a lifetime history of more than 12 months of lactation were less likely to have hypertension (odds ratio [OR] 0.88, P<.001), diabetes (OR 0.80, P<.001), hyperlipidemia (OR 0.81, P<.001), or cardiovascular disease (OR 0.91, P=.008) than women who never breast-fed, but they were not less likely to be obese. In models adjusted for all above variables and BMI, similar relationships were seen. Using multivariate adjusted prevalence ratios from generalized linear models, we estimate that among parous women who did not breast-feed compared with those who breast-fed for more than 12 months, 42.1% versus 38.6% would have hypertension, 5.3% versus 4.3% would have diabetes, 14.8% versus 12.3% would have hyperlipidemia, and 9.9% versus 9.1% would have developed cardiovascular disease when postmenopausal. Over an average of 7.9 years of postmenopausal participation in the Women's Health Initiative, women with a single live birth who breast-fed for 7-12 months were significantly less likely to develop cardiovascular disease (hazard ratio 0.72, 95% confidence interval 0.53-0.97) than women who never breast-fed., Conclusion: Among postmenopausal women, increased duration of lactation was associated with a lower prevalence of hypertension, diabetes, hyperlipidemia, and cardiovascular disease.

Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and is important to carcinogenesis. Previous studies relating circulating levels of VEGF to breast cancer have been limited by small numbers of participants and lack of adjustment for confounders. We studied the association between serum VEGF and breast cancer in an unmatched case-control study of 407 pre- and postmenopausal women (n = 203 cases, n = 204 controls). Logistic regression was used to model the breast cancer risk as a function of natural log transformed VEGF levels adjusted for age, Gail score, education, physical activity, history of breastfeeding, serum testosterone, and hormone therapy (HT) use. The majority of the population was postmenopausal (67.6%) and the average age was 56 years; age and menopausal status were similar among cases and controls. Geometric mean VEGF levels were non-significantly higher in cases (321.4 pg/ml) than controls (291.4 pg/ml; p = 0.21). In a multivariable model, the odds of breast cancer was 37% higher for women with VEGF levels > or =314.2 pg/ml compared to those with levels below 314.2 pg/ml, albeit not significantly (p = 0.16). There was no interaction between VEGF and menopausal status (p = 0.52). In this case-control study, VEGF was not significantly associated with breast cancer risk in pre- and postmenopausal women.