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Passive educational techniques (such as lectures) are thought to be less productive than active learning.We examined whether preparing for and participating in a debate would be an effective, active way to learn about a controversial topic.We compared quiz performance in residents who attended a lecture to residents who prepared for/participated in a debate. Twelve residents each participated in one lecture session and one debate session. Learning was evaluated via a quiz. Quizzes were given twice: before the debate/lecture and 1 week after the debate/lecture. Quiz scores were compared using repeated measures analysis of variance, with a p value of.05 considered significant. A survey evaluating the usefulness of debating was given to all participants.There was a statistically significant difference in the pretest mean quiz score between the debate and lecture groups: 78.3% and 52.5%, respectively (p = .02). Similarly, on posttest quizzes, the average debater scored 85.8%, versus 61.7% for the lecture group (p = .003). Although no one in the debate group scored lower on a follow-up quiz, 3 residents in the lecture group did worse on follow-up.When learning about a controversial topic, residents who prepared for/participated in a debate achieved higher quiz scores and were better at retaining information than those who attended a lecture. When faced with teaching a controversial topic, organizing a debate may be more effective than giving a lecture.

Objective. The purpose of this study was to evaluate the usefulness of virtual spherical tissue sampling using 3-dimensional (3D) ultrasound power Doppler angiography to enhance differentiation between normal and pathologic ovaries. Methods. Twenty-seven cases with ovarian tumors were analyzed: 14 with invasive cancers and 13 with borderline tumors confirmed by surgery. The control subjects consisted of 53 healthy ovulating women. Ultrasound scans were done, and 3D volumes were analyzed with 3-/4-dimensional software for personal computers based on 3D vascularity indices: the vascularization index, flow index, and vascularization-flow index. A virtual spherical tissue sample of 1 cm 3 was taken from the place of the highest vessel density contained completely within the contours of the ovary. Calculations for the whole solid volume were done for comparison. Results. Vascularity indices for both 1-cm 3 spherical samples and whole dense parts of the ovaries were compared in the following groups: (1) ovarian tumors versus controls, (2) normal ovaries in the proliferative versus secretory phase, (3) invasive cancers versus borderline tumors, (4) invasive cancers versus normal ovaries, and (5) borderline tumors versus normal ovaries. Spherical 1-cm 3 sampling achieved a higher degree of discrimination between the groups compared with the whole solid-part approach. Conclusions. Spherical 1-cm 3 sampling of ovarian tissue with 3D ultrasound power Doppler angiography is a sensitive and promising approach to differentiate between ovarian tumors and normal ovaries. It opens the possibility to implement objective computerized positioning, standardized comparison, and analysis of ovarian tumors.

To evaluate the associations of breast cancer risk with polymorphisms in the XPC and XPD/ERCC2 DNA nucleotide excision repair genes, a case-control study nested within a prospective cohort of 14,274 women was conducted. Genotypes were characterized for 612 incident, invasive breast cancer cases and their 1:1 matched controls. The homozygous variant of a poly(AT) insertion/deletion polymorphism in intron 9 of the XPC gene (XPC-PAT+/+), was associated with breast cancer risk [odds ratio (OR) = 1.45, 95% confidence interval: 1.07-1.97], after adjustment for other breast cancer risk factors. The breast cancer risk associated with XPC-PAT+/+ did not differ by age at diagnosis. There was an indication of an interaction (p = 0.08) between the XPC-PAT+/+ genotype and cigarette smoking. Ever smokers with the XPC-PAT+/+ genotype were at elevated risk of breast cancer (OR = 1.56, CI: 0.95-2.58), but no differences were observed among never smokers. Analyses of the ERCC2 Lys751Gln polymorphism did not show an association with breast cancer risk, either overall or at younger ages. The results suggest that breast cancer risk is related to the XPC haplotype tagged by the XPC-PAT+/+ insertion-deletion polymorphism in intron 9. Further study of the XPC haplotypes and their interactions with smoking in relation to breast cancer risk is needed.

Background: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy. Methods: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Results: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the 33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II. Conclusions: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2489–93)

Extra-amniotic saline infusion (EASI) via a Foley catheter has been thought to be comparable in efficacy to other induction and cervical ripening methods. This study examines the risk of cesarean delivery associated with EASI compared with spontaneous labor and other methods of cervical ripening. A retrospective cohort study based upon deliveries at Bellevue Hospital Center from August 2000 to December 2002 was conducted. Three groups were identified: EASI, other methods of induction such as prostaglandins and oxytocin administration, and spontaneous labor. Pairwise comparisons were performed using analysis of variance and multivariate logistic regression analysis to control for confounding variables. There were 625 charts evaluated: including 171 with EASI, 190 with other induction methods, and 264 with spontaneous labor. The rates of cesarean section were 33.9%, 17.9%, and 7.2%, respectively. When compared with spontaneous labor, there was a higher risk of cesarean delivery for subjects induced with other methods (adjusted odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.5; p < 0.001), and for those induced with EASI (adjusted OR, 5.5; 95% CI, 3.1 to 9.9; p < 0.001). When EASI was compared with other methods of induction, the risk of cesarean delivery was still increased (adjusted OR, 2.3; 95% CI, 1.4 to 3.8; p = 0.001). EASI is associated with an increased risk of cesarean delivery compared with spontaneous labor and other methods of cervical ripening.

Background: Dairy foods and their constituents (lactose and calcium) have been hypothesized to promote ovarian carcinogenesis. Although case-control studies have reported conflicting results for dairy foods and lactose, several cohort studies have shown positive associations between skim milk, lactose, and ovarian cancer. Methods: A pooled analysis of the primary data from 12 prospective cohort studies was conducted. The study population consisted of 553,217 women among whom 2,132 epithelial ovarian cases were identified. Study-specific relative risks and 95% confidence intervals were calculated by Cox proportional hazards models and then pooled by a random-effects model. Results: No statistically significant associations were observed between intakes of milk, cheese, yogurt, ice cream, and dietary and total calcium intake and risk of ovarian cancer. Higher lactose intakes comparing ≥30 versus Discussion: Overall, no associations were observed for intakes of specific dairy foods or calcium and ovarian cancer risk. A modest elevation in the risk of ovarian cancer was seen for lactose intake at the level that was equivalent to three or more servings of milk per day. Because a new dietary guideline recommends two to three servings of dairy products per day, the relation between dairy product consumption and ovarian cancer risk at these consumption levels deserves further examination. (Cancer Epidemiol Biomarkers Prev 2006;15(2):364–72)

BACKGROUND Uterine leiomyomas are extremely common and a major cause of pelvic pain, bleeding, infertility, and the leading indication for hysterectomy. Familial and epidemiological studies provide compelling evidence that genetic alterations play an important role in leiomyoma development. METHODS Using Affymetrix U133A GeneChip we analysed expression profiles of 22,283 genes in paired samples of leiomyoma and adjacent normal myometrium. We compared our results with previously published data on gene expression in uterine leiomyoma and identified the overlapping gene alterations. RESULTS We detected 80 genes with average differences of > or = 2-fold and false discovery rates of < 5% (14 overexpressed and 66 underexpressed). A comparative analysis including eight previous gene expression studies revealed eight prominent genes (ADH1, ATF3, CRABP2, CYR61, DPT, GRIA2, IGF2, MEST) identified by at least five different studies, eleven genes (ALDH1, CD24, CTGF, DCX, DUSP1, FOS, GAGEC1, IGFBP6, PTGDS, PTGER3, TYMS) reported by four studies, twelve genes (ABCA, ANXA1, APM2, CCL21, CDKN1A, CRMP1, EMP1, ESR1, FY, MAP3K5, TGFBR2, TIMP3) identified by three studies, and 40 genes reported by two different studies. CONCLUSIONS Review of gene expression data revealed concordant changes in genes regulating retinoid synthesis, IGF metabolism, TGF-beta signaling and extracellular matrix formation. Gene expression studies provide clues to the relevant pathways of leiomyoma development.

Objective The purpose of this study was to compare the performance of the transabdominal versus the transvaginal route for the multifetal pregnancy reductions. Study design Two hundred ninety consecutive cases of multifetal pregnancy reduction were reviewed. Two hundred three reductions (70.0%) were done transabdominally; 75 cases (25.9%) were done transvaginally, and 12 cases (4.1%) used both routes. The indications for the transvaginal route were extreme obesity, abdominal scars, or if the lower fetus could not be reached transabdominally. Two hundred seventy-one women were delivered of live born babies after 24 weeks (group 1). Nineteen cases had pregnancy losses ≤24 weeks (group 2). Results The complete pregnancy loss rate was 6.5% (19/290 cases). Total pregnancy loss rates of multifetal pregnancy reduction were 3.5% (7/203 reductions) for the transabdominal route and 13.3% (10/75 reductions) for the transvaginal route (P = .004). Overall pregnancy losses were 4.8% for starting with twins, 6.6% for starting with triplets, 1.8% for starting with quadruplets, 14.3% for starting with quintuplets, and 14.3% with starting numbers of ≥6 fetuses. For finishing numbers, total pregnancy losses were 5.1% for ending with a singleton infant, 6.6% for ending with twins, and 0% for ending with triplets. Significant differences in complete pregnancy loss were observed between transabdominal and transvaginal routes for starting with triplets (2.7% for transabdominal versus 16.7% for transvaginal; P = .006) and for finishing with a single fetus (0% for transabdominal versus 20% for transvaginal; P Conclusion The multifetal pregnancy reduction success rate was higher with the transabdominal route compared with the transvaginal route. Significant differences in favor of the transabdominal route were observed for starting with triplets or finishing with a single fetus. The transvaginal route should be reserved only for cases in which the transabdominal approach is hard or impossible to perform. The performance of the procedure at 12 to 13 weeks of gestation enables structural evaluation of the fetuses before reduction.

Objectives The objective of this study was to determine the extent to which normal fetal anatomy can be detected between 11- and 14-week scan by sonographers in the US. Study design In a prospective cross-sectional study, 223 unselected women underwent a detailed assessment of fetal anatomy at 11 to 13 and 6/7 weeks by sonographers with transabdominal and/or transvaginal transducers. Thirty-seven structures were examined. Two groups were identified: group I: 121 patients between 11 and 12 weeks, and group II: 102 patients between 13 and 14 weeks. Results Structures other than the posterior fossa, heart, genitalia, and the sacral spine were seen between 64% to 99% for group I, and 72% to 98% for group II. The following structures were detected with statistically significantly higher rates in group II compared with group I: cerebellum, posterior fossa, face, 4-chamber view left ventricular outflow tract, aortic arch, ductal arch, kidneys, and genitalia. Comparing the patients of group I and group II, the transvaginal scans yielded a higher detection rate of structures than do the transabdominal scans. Conclusion Anatomic surveys between 11 and 14 weeks can be performed by sonographers with good detection rates of most structures. Using the vaginal probe compared with the abdominal probe improved the detection rate at 13 to 14 weeks as well as 11 to 12 weeks. If early fetal structure evaluation is to become customary in the US, the present practice of experienced and trained sonographers to scan such patients can be maintained.

Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog2: 1.07 (0.99–1.17)), or with any of the examined subgroups. Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.

Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p

Background: It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16α-hydroxylation pathway may be inversely associated with breast cancer risk. Methods: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and the 2-OHE1:16α-OHE1 ratio in a case–control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16α-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation. Results: Overall, no significant associations were observed between breast cancer risk and circulating levels of 2-OHE1, 16α-OHE1, or their ratio in either cohort and in combined analyses. For 2-OHE1, there was evidence of heterogeneity by ER status in models adjusting for estrone (P ≤ 0.03). We observed a protective association of 2-OHE1 with ER+ breast cancer [multivariate-adjusted OR for a doubling of 2-OHE1, 0.67 (95% confidence interval [CI], 0.48–0.94; P = 0.02)]. Conclusions: In this study, higher levels of 2-OHE1 were associated with reduced risk of ER+ breast cancer in postmenopausal women after adjustment for circulating estrone. Impact: These results suggest that taking into account the levels of parent estrogens and ER status is important in studies of estrogen metabolites and breast cancer. Cancer Epidemiol Biomarkers Prev; 23(7); 1290–7. ©2014 AACR.

Introduction: Experimental evidence suggests a protective role for circulating 25-hydroxyvitamin D (25(OH) D) in breast cancer development, but the results of epidemiological studies have been inconsistent. Methods: We conducted a case-control study nested within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Mammary Screening Cohort. Blood samples were collected at enrollment, and women were followed up for breast cancer ascertainment. In total, 1,585 incident breast cancer cases were individually-matched to 2,940 controls. Of these subjects, 678 cases and 1,208 controls contributed two repeat blood samples, at least one year apart. Circulating levels of 25(OH) D were measured, and multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: No association was observed between circulating levels of 25(OH) D and overall breast cancer risk (multivariate-adjusted model OR = 0.94, 95% CI = 0.76-1.16 for the highest vs. lowest quintile, ptrend = 0.30). The temporal reliability of 25(OH)D measured in repeat blood samples was high (intraclass correlation coefficients for season-adjusted 25(OH) D > 0.70). An inverse association between 25(OH) D levels and breast cancer risk was observed among women who were = 45 years of age (ORQ5-Q1 = 0.48, 95% CI = 0.30-0.79, ptrend = 0.01) or premenopausal at enrollment (ORQ5-Q1 = 0.67, 95% CI = 0.48-0.92, ptrend = 0.03). Conclusions: Circulating 25(OH) D levels were not associated with breast cancer risk overall, although we could not exclude the possibility of a protective effect in younger women. Recommendations regarding vitamin D supplementation should be based on considerations other than breast cancer prevention.

PurposeDiabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan).MethodsThe pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (

PURPOSE: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. PATIENTS AND METHODS: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. RESULTS: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. CONCLUSION: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.

Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk. This work was supported by National Cancer Institute grants R01 CA081212, R01 CA098661 and P30 CA016087 and Center grant ES000260 from the National Institute of Environmental Health Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The incremental iterative technique is used to effectively couple for three-dimensional transonic flow about a twisted unswept rectangular wing, an aerodynamic solution for the pressure distribution with a structural solution for the corresponding deflections and, using the quasianalytical approach, simultaneously obtain the aerodynamic, structural, and coupling sensitivity derivatives for the fully coupled system. The solution includes aerodynamic sensitivities for nine design variables at all flowfield points, structural sensitivities for four design variables at 490 points on the wing, and 450 coupling sensitivities. Subsequently, fully coupled system sensitivity derivatives are obtained. The results often show significant differences between the discipline and system sensitivity derivatives and that the system derivatives are sensitive to the location and number of coupling derivatives.

Background: Lung cancer in never smokers is a significant contributor of cancer mortality. As the incidence of lung cancer in never smokers is increasing, there is a need to investigate risk factors for lung cancer in this population. There is data to support that polyomaviruses are potentially carcinogenic in the human lung. We explored the role of polyomaviruses in lung cancer development in never smokers using a multiplex assay to detect serum antibodies to viral capsid proteins. Methods: We conducted a nested case-control study of never-smoking cases of lung cancer identified from four established prospective cohorts- NYU Women's Health Study (NYU-WHS), Janus Serum Bank, Shanghai Women's Health Study (SWHS) and Singapore Chinese Health Study (SCHS). Controls were matched to cases on gender, never-smoking status, age and calendar period of entry. Serological analysis was performed using a 100 μL pre-diagnostic serum sample at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, Germany using fluorescent bead-based multiplex serology and included antibodies to viral capsid protein-1 and T-antigens of 9 human polyomaviruses: JC virus, BK virus, KI virus, WU virus, Trichodysplasia Spinulosa-associated Polyoma Virus, Merkel Cell Polyoma Virus, Human Polyoma Virus 6, Human Polyoma Virus 7 and Human Polyoma Virus 10. Results: The final analysis included 511 cases and 508 controls. Mean age of participants was 56.1±11.0 years. SWHS and SCHS included only Asian participants. NYU-WHS and SWHS had only female participants. Nearly 85% of the participants in our pooled analysis were females and 74% were Asians. Seropositivity for each polyomavirus showed significant heterogeneity by study but overall there were no statistical significant differences between cases and controls for any of the polyomaviruses. 72.0% of the cases and 71.5% of the controls were seropositive for JC virus antibody. Seropositivity for BK virus was higher at 89.0% in cases and 89.8% in controls. We did not find any difference in seropositivity between cases and controls in our stratified analysis based on gender, histology or time interval from sample collection to cancer diagnosis. We also performed sensitivity analyses and found the seroprevalence data to be very robust to alterations in the MFI cutpoints. Conclusions: Our study is the largest epidemiological study in never smokers to investigate the role of polyomaviruses in lung cancer development. We did not find a significant difference in serological measurements of antibodies against each of the polyomaviruses between the cases and controls. Future research to evaluate the relationship between polyomaviruses and lung carcinogenesis should focus on evaluating viral replication in tumor in combination with serological markers of infection especially as antibody reactivities can vary considerably across different populations and geographical areas as demonstrated by our study. Citation Format: Jyoti Malhotra, Tim Waterboer, Michael Pawlita, Angelika Michel, Qiuyin Cai, Wei Zheng, Qing Lan, Nathaniel Rothman, Hilde Langseth, Tom K. Grimsrud, Jian-Min Yuan, Woon-Puay Koh, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Paolo Boffetta. Serum biomarkers of polyomavirus infection and risk of lung cancer in never smokers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4290.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of > 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

BACKGROUND: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. METHODS: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). RESULTS: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. CONCLUSION: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.

Background It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy. Methods In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry. Results We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis. Conclusions This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process.

Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries.

The objective of the study was to investigate whether resistance to annexin A5 anticoagulant activity (AnxA5) occurs in women with histories for obstetric complications of antiphospholipid syndrome (Obs-APS) and whether this correlates with antibody recognition of domain 1 of ?2-glycoprotein.One hundred thirty-six women with antiphospholipid antibodies, including 70 with histories for Obs-APS and 30 controls, were investigated.Women with Obs-APS showed resistance to AnxA5 activity (median, 216%; range, 130-282% vs controls; median, 247%; range, 217-283%; P

The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer. Cancer Prev Res; 4(9); 1457–64. ©2011 AACR.

Background: Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A1 versus A2 variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A1 allele would confer greater risk than A2 allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk. Methods: We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression. Results: An increased risk was observed in participants with A1 but not A2 alleles. Compared with subjects with genotype O/O, genotypes A2/O, A2/A1, A1/O, and A1/A1 had ORs of 0.96 (95% CI, 0.72–1.26), 1.46 (95% CI, 0.98–2.17), 1.48 (95% CI, 1.23–1.78), and 1.71 (95% CI, 1.18–2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A1, and A2 were 1.00 (95% CI, 0.87–1.14), 1.38 (95% CI, 1.20–1.58), and 0.96 (95% CI, 0.77–1.20); P, O01 versus O02 = 0.94, A1 versus A2 = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63). Conclusions: Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk. Impact: These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34. Cancer Epidemiol Biomarkers Prev; 19(12); 3140–9. ©2010 AACR.

Background Cytokines are involved in the development of chronic diseases, including cancer. It is important to evaluate the temporal reproducibility of cytokines in plasma prior to conducting epidemiologic studies utilizing these markers. Findings We assessed the temporal reliability of CRP, 22 cytokines and their soluble receptors (IL-1α, IL-1β, IL-1RA, IL-2, sIL-2R, IL-4, IL-5, IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, TNFα, sTNF-R1, sTNF-R2, IFNα, IFNγ) and eight growth factors (GM-CSF, EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2) in repeated EDTA plasma samples collected an average of two years apart from 18 healthy women (age range: 42-62) enrolled in a prospective cohort study. We also estimated the correlation between serum and plasma biomarker levels using 18 paired clinical samples from postmenopausal women (age range: 75-86). Twenty-six assays were able to detect their analytes in at least 70% of samples. Of those 26 assays, we observed moderate to high intra-class correlation coefficients (ICCs)(ranging from 0.53-0.89) for 22 assays, and low ICCs (0-0.47) for four assays. Serum and plasma levels were highly correlated (r > 0.6) for most markers, except for seven assays (r < 0.5). Conclusions For 22 of the 31 biomarkers, a single plasma measurement is a reliable estimate of a woman's average level over a two-year period.

Udgivelsesdato: 2010-Jan-4 A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.

Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (P(trend) = 0.68) or by sex (men, P(trend) = 0.50; women, P(trend) = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects.

BackgroundObesity has been proposed as a risk factor for pancreatic cancer.MethodsPooled data were analyzed from the National Cancer Institute Pancreatic Cancer Cohort Consortium (PanScan) to study the association between prediagnostic anthropometric measures and risk of pancreatic cancer. PanScan applied a nested case-control study design and included 2170 cases and 2209 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight, height, waist circumference, and waist to hip ratio as well as conventional BMI categories (underweight, or = 35.0). Models were adjusted for potential confounders.ResultsIn all of the participants, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs lowest BMI quartile, 1.33; 95% CI, 1.12-1.58; P(trend) < .001). In men, the adjusted OR for pancreatic cancer for the highest vs lowest quartile of BMI was 1.33 (95% CI, 1.04-1.69; P(trend) < .03), and in women it was 1.34 (95% CI, 1.05-1.70; P(trend) = .01). Increased waist to hip ratio was associated with increased risk of pancreatic cancer in women (adjusted OR for the highest vs lowest quartile, 1.87; 95% CI, 1.31-2.69; P(trend) = .003) but less so in men.ConclusionsThese findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women.

A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18–1.62], 1.47 (95% CI, 1.07–2.02), and 1.53 (95% CI, 1.21–1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13–1.58) and 1.61 (95% CI, 1.22–2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14–1.85) and 2.42 (1.28–4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03–3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk. Cancer Res; 70(3); 1015–23

We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

Udgivelsesdato: 2009-Sep We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

Objective. The purpose of this study was to assess the vascular indices generated by 3-dimensional (3D) power Doppler angiography by evaluating the cyclic changes in the vascularity of normal ovaries, including those that were ovulating, nonovulating, and hormonally suppressed. Methods. In this prospective longitudinal observational study, a cohort of premenopausal regularly menstruating women with no known ovarian disease underwent 3D power Doppler imaging every 2 to 3 days for the duration of 1 menstrual cycle. Four indices were generated: vascularization index (VI), flow index (FI), vascularization-flow index (VFI), and mean grayness. Comparisons of vascularity were made between ovulating, nonovulating, and hormonally suppressed ovaries. Normal ranges were established and graphed longitudinally. Results. Eighteen participants (36 ovaries) ages 28 to 45 years underwent an average of 10 examinations, yielding 368 acquired ovarian volumes for analysis. Seven participants used hormonal contraception. The VI, FI, and VFI were closely correlated (Pearson product moment correlation coefficients, 0.52–0.95). The vascular indices of ovulating ovaries were significantly higher than those of nonovulating ovaries (VI, FI, and VFI, all P < .001), with the largest discrepancies during the luteal phase. Hormonally suppressed ovaries had significantly lower vascularity throughout the cycle (VI, P < .002; FI, P < .001; VFI, P < .007). The vascular indices of all groups appeared to drop during the late follicular period and then rise again. Conclusions. The VI would suffice as the principal vascular parameter for 3D power Doppler analysis. Preovulatory scans may be more useful for distinguishing pathologic vascularization. Hormonally suppressed ovaries have significantly lower vascularity throughout the cycle. Normal-appearing ovaries with vascular indices above the normal ranges established by these data may warrant further investigation. Key words: flow index; ovarian blood flow; ovarian vascularity; sonographic angiography; 3-dimensional power Doppler sonography; vascularization-flow index; vascularization index.

Objective: Chinese women have been shown to have a higher incidence of severe perineal laceration compared to other ethnic groups. We sought to test the hypothesis that this risk is related to body mass index (BMI) or to a relative fetal-maternal size disproportion as measured by the ratio of the newborn birthweight to maternal BMI (BW:BMI). Methods: A retrospective cohort study was performed using a pre-existing obstetric database. Third- and fourth-degree perineal lacerations served as the primary outcome of interest. Logistic regression was used to compare Chinese women to other ethnic groups and adjust for confounders. Results: Three thousand and eighty-five singleton vaginal deliveries were identified, with BMI data available for 2281. Chinese women had a greater risk for severe perineal laceration compared to Caucasian (OR: 3.22; 95% Cl: 0.73-14.32) and Hispanic women (OR: 2.88; 95% Cl: 1.92-4.30). Multivariate analysis found that newborn birth weight plays a role (OR: 1.0012; 95% Cl: 1.0007-1.0016), but BMI alone did not explain the discrepancy (P=0.89). However, the BW:BMI ratio appears to be a stronger predictor of laceration rate than either variable alone (OR: 1.011; 95% Cl: 1.003-1.020). Conclusion: The higher risk of severe perineal laceration in Chinese women compared to other ethnicities can be attributed, in part, to a relative fetal-maternal size disproportion.

We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59–2.01). In addition, there was no evidence of an interaction effect betweenVDRSNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.

Inflammatory processes may influence the risk of epithelial ovarian cancer, but available epidemiological evidence is limited and indirect. Circulating C-reactive protein (CRP), a sensitive marker of inflammation, may serve as a direct biological marker of an underlying association. The association between ovarian cancer risk and pre-diagnostic circulating CRP was tested in a case–control study nested within three prospective cohorts from Sweden, USA, and Italy. The study included 237 cases and 427 individually matched controls. CRP was measured in stored blood samples by high-sensitivity immunoturbidimetric assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. Overall, CRP was not related to risk of ovarian cancer. However, a marked increase in risk was observed for CRP concentrations >10 mg/l: OR (95% CI) 4.4 (1.8–10.9), which remained significant after limiting analyses to cases diagnosed more than two or five years after blood donation (OR 3.0 (1.2–8.0) and 3.6 (1.0–13.2), respectively). Risk of mucinous tumors increased with high CRP, but the number of cases in this analysis was small. Study results offer additional support to the concept that chronic inflammation plays a role in epithelial ovarian cancer.

Our study aimed to identify perceptions Latina women have about four different contraceptive methods and to investigate whether religiosity and acculturation play a role in their contraceptive choice. An observational cross-sectional study was performed at Bellevue Hospital. A questionnaire was given to women in the gynecology outpatient clinics asking about: oral contraceptive pills (OCP’s), injectable contraception (DMPA), the Intrauterine device (IUD) and the Ortho-Evra Patch (Patch). In the 102 complete surveys, self identified Latina women were not convinced of the safety of OCPs and DMPA (less than 50% perceived them to be safe) and largely uncertain about the Patch and IUD. Latinas also demonstrated more negative beliefs about the side effects of OCPs and DMPA. In particular, they were concerned about weight gain, method reversibility, and bleeding. There was no substantial correlation between religiosity and contraceptive beliefs. Low level acculturated women were more likely to believe that the IUD and OCPs were harmful, as opposed to their more acculturated counterparts who demonstrated more negative beliefs about the Patch. Overall, Latina women in this study tended to overrate the risks associated with contraceptive use, particularly OCPs and DMPA. The markedly low method confidence suggested by high rates of “unsure” answers is a possible explanation for why Latinas are less adherent with birth control than their white counterparts.

Highly penetrant, but rare, mutations in genes involved in double-strand break repair (i.e., BRCA1 and BRCA2 ) are associated with a risk for breast cancer of 40% to 65% by age 70 years ([1][1], [2][2]). Polymorphisms in other double-strand break repair genes are thought to contribute to the risk

Study Objective: To characterize and compare acceptability of human papillomavirus (HPV) vaccination by Latino parents at an urban medical center in the United States and a community hospital in El Salvador. Design: After reading an information sheet on HPV, 148 subjects at Bellevue Hospital in New York City and 160 subjects at Hospital Nacional de Santa Gertrudis in San Vicente, El Salvador, completed a survey. Results were analyzed using chi-square, Fisher's exact test, and Student's t-tests. Results and Conclusions: Parental acceptance of HPV vaccination was higher in a sample of Salvadoran subjects than in a sample of U.S. Latinas (P! 0.001 for daughters and sons). Reasons for objecting to HPV vaccination differ in the two locations. There are important differences between Salvadoran and U.S. subjects. Salvadorans are more accept- ing of HPV vaccination, and parental acceptance is unlikely to be a barrier to widespread vaccination in El Salvador. Tar- geted educational materials are needed in both locations.

Background: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent. Methods: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12 prospective cohort studies from North America and Europe. The study population consisted of 531,583 women among whom 2,036 epithelial ovarian cancer cases were identified. To summarize associations, study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Results: Women with height ≥1.70 m had a pooled multivariate RR of 1.38 [95% confidence interval (95% CI), 1.16-1.65] compared with those with height Conclusion: Height was associated with an increased ovarian cancer risk, especially in premenopausal women. BMI was not associated with ovarian cancer risk in postmenopausal women but was positively associated with risk in premenopausal women. (Cancer Epidemiol Biomarkers Prev 2008;17(4):902–12)

BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Introduction: Ovarian cancer is a heterogeneous disease with about half of patients dying within 3 years, but a third surviving at least 10 years, potentially reflecting differences not only for stage, but also in tumor biology. We evaluated if known and putative ovarian cancer risk factors were differentially associated with tumor aggressiveness, defined as rapidly fatal (death within 3 years) and less aggressive (all others). We assessed oral contraceptive (OC) use, parity, tubal ligation, height, body mass index (BMI), family history of breast or ovarian cancer, age at menarche and menopause, and smoking using pooled data from 18 prospective cohort studies. Methods: Ovarian cancer characteristics and diagnosis dates were abstracted from pathology reports or cancer registries; registries were used to ascertain vital status and date of death. We used competing risks Cox proportional hazards models to compute relative risks (RR) and 95% confidence intervals (CI) by tumor aggressiveness, stratified on study, age, and birth year, and adjusted for parity and OC use; p-heterogeneity (p-het) was evaluated by likelihood ratio tests. Results: Among 3,811 cases with known vital status and the potential for at least 3 years of post-diagnosis follow-up, 1,897 (49.8%; median survival=1yr) were rapidly fatal and 1,914 (50.2%; median survival=18yr) were less aggressive. 66% of rapidly fatal and 55% of less aggressive cases were of serous histology. Stronger inverse associations were observed for less aggressive than for rapidly fatal disease for tubal ligation (RR, yes vs. no=0.67 vs. 1.06, respectively; p-het=0.004), parity (RR, per child=0.87 vs. 0.93; p-het=0.001) pack years of smoking (RR, >30 pack-years vs. never=0.78 vs. 1.14; p-het=0.01), and suggestively for family history of breast cancer (RR, yes vs. no=1.15 vs. 0.99, p-het=0.18). Conversely, women with a BMI>30 vs. >22-25 kg/m2 were at higher risk of rapidly fatal disease (RR=1.40), but not less aggressive disease (RR=1.00; p-het=0.04). Associations for other risk factors did not differ by aggressiveness. Discussion: In this prospective analysis, we observed differential associations by tumor aggressiveness for some risk factors. The potentially stronger association of a family history of breast cancer with less aggressive disease is supported by reports of better survival in BRCA mutation carriers. Associations of parity, tubal ligation, and smoking with less aggressive disease may reflect differential associations by histology; additional analyses will account for histology and stage. The BMI association with rapidly fatal disease suggests that metabolic dysfunction may play a role in tumor aggressiveness. Our results support that pre-diagnostic factors may influence ovarian cancer development and aggressivness. Ultimately, understanding a woman's risk profile with respect to risk of rapidly fatal versus less aggressive disease at diagnosis may aid in determining the most optimal treatment strategy for long term survival. Citation Format: Shelley S. Tworoger, Elizabeth M. Poole, Alan A. Arslan, Lesley M. Butler, Victoria Kirsh, James V. Lacey, Jr., I-Min Lee, Alpa V. Patel, Kim Robien, Thomas Rohan, Dale P. Sandler, Leo J. Schouten, V. Wendy Setiawan, Kala Visvanathan, Elisabete Weiderpass, Emily White, Nicolas Wentzensen, for the OC3. Ovarian cancer risk factor associations by tumor aggressiveness in the ovarian cancer cohort consortium (OC3) [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS10.

Background: A subset of high grade serous carcinomas may arise from the fallopian tube, while some endometrioid and clear cell carcinomas may derive from endometrial tissue. Previous studies have suggested differences in ovarian cancer risk factors by histologic subtypes, but had limited sample sizes. In the Ovarian Cancer Cohort Consortium (OC3), we evaluated associations of reproductive, hormonal, demographic and lifestyle factors, and family history of cancer with ovarian cancer subtypes. Identification of potential differences in associations among subtypes is important for clarifying ovarian cancer etiology and for developing novel prevention and risk prediction approaches. Methods: Among over 1.2 million women from 21 cohort studies, 4,347 ovarian cancers with histology information were identified during follow-up (3223 serous, 555 endometrioid, 316 mucinous, 253 clear cell). We used competing risks Cox proportional hazards regression to compute risk factor associations by histologic subtype. Models were stratified on study and year of birth and adjusted for age, parity and oral contraceptive use; subtype heterogeneity was evaluated by a likelihood ratio test. Unsupervised hierarchical clustering was used to evaluate patterns of risk factors by histology. Results: Most risk factors showed significant heterogeneity across histologic subtypes. Higher parity was most strongly associated with lower risks of endometrioid (RR per child: 0.79; 95%CI: 0.74-0.85) and clear cell (RR: 0.69; 95%CI: 0.61-0.78) carcinomas (p-het5 years) was associated with endometrioid carcinomas (RR: 2.23; 95% CI: 1.46-3.42) and serous carcinomas (RR: 1.66; 95% CI: 1.44-1.92), and inversely associated with clear cell carcinomas (RR: 0.43; 95% CI: 0.20-0.91; p-het = 0.001). Family history of breast cancer was associated with increased risk of serous carcinomas (RR:1.13; 95% CI:1.02-1.27) and endometrioid carcinomas (RR: 1.44; 95% CI: 1.12-1.87; p-het = 0.02). Smoking (per 20 pack years) showed a positive association with mucinous carcinomas (RR: 1.38; 95% CI: 1.09-1.75) and an inverse association with clear cell carcinomas (RR:0.62; 95% CI: 0.46-0.85; p-het = 0.001). In unsupervised hierarchical clustering, serous and mucinous carcinomas clustered in one group and endometrioid and clear cell carcinomas in the other. Conclusion: Our results demonstrate heterogeneous associations of risk factors with ovarian cancer subtypes, supporting the hypothesis that the subtypes develop through different pathways. Most established risk factors were more strongly associated with non-serous carcinomas, suggesting that risk prediction may be more challenging for serous cancers, the most fatal subtype. Citation Format: Nicolas A. Wentzensen, Elizabeth Poole, Alan A. Arslan, Alpa V. Patel, V Wendy Setiawan, Kala Visvanathan, Elisabete Weiderpass, Emily White, Hans-Olov Adami, Louise A. Brinton, Leslie Bernstein, Julie Buring, Lesley M. Butler, Saioa Chamosa, Tess V. Clendenen, Laure Dossus, Renee Fortner, Susan M. Gapstur, Mia M. Gaudet, Inger Torhild Gram, Patricia Hartge, Judith Hoffman-Bolton, Annika Idahl, Michael Jones, Rudolf Kaaks, Vivki Kirsh, Woon-Puay Koh, James V. Lacey, I-Min Lee, Eva Lundin, Melissa Merritt, Ulrike Peters, Jenny Poynter, Sabina Rinaldi, Kim Robien, Thomas Rohan, Dale P. Sandler, Leo J. Schouten, Louise Sjöholm, Sabina Sieri, Anthony Swerdlow, Anne Tjønneland, Britton Trabert, Lynne Wilkens, Alicja Wolk, Hannah P. Yang, Anne Zeleniuch-Jacquotte, Shelley S. Tworoger. Ovarian cancer risk factors by histologic subtypes: evidence for etiologic heterogeneity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 854. doi:10.1158/1538-7445.AM2015-854

Epidemiologic evidence suggests that a full-term pregnancy may affect maternal risk of breast cancer later in life. The objective of this cross-sectional study was to compare circulating levels of maternal hormones affecting breast differentiation (human chorionic gonadotropin and prolactin) and proliferation [α-fetoprotein, insulin-like growth factor I (IGF-I), and estradiol] between women at a low to moderate risk (Asians and Hispanics), as compared with women at a high risk for breast cancer (Caucasians and African-Americans). Between May 2002 and December 2004, a total of 586 pregnant women were approached during a routine prenatal visit. Among them, 450 women (206 Caucasian, 126 Asian, 88 Hispanic, and 30 African-American) met the inclusion criteria and signed the informed consent. Only singleton pregnancies were considered. Blood samples were drawn during the second trimester of pregnancy. Laboratory analyses were done using the IMMULITE 2000 immunoassay system. Gestational age standardized mean levels of estradiol, IGF-I, and prolactin were significantly higher in Hispanic women compared with Caucasian women. Mean concentration of IGF-I was significantly higher in African-American women compared with Caucasian and Asian women. No significant differences in pregnancy hormone levels were observed between Caucasian and Asian (predominantly second-generation Chinese) women in this study. Irrespective of ethnicity, women who had their first pregnancy had substantially higher mean levels of α-fetoprotein, human chorionic gonadotropin, estradiol, and prolactin compared with women who previously had at least one full-term pregnancy. These data suggest that circulating pregnancy hormone levels may explain some of the ethnic differences in breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2123–30)

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.

Purpose The aim of the study is to determine the reliability during a 2-year period of several newly developed iron-related assays to assess their potential for use in prospective epidemiologic studies. Methods We assessed the temporal reliability of several iron-related assays by using three serum samples collected at yearly intervals from 50 postmenopausal participants in a large prospective study. Results We observed high reliability coefficients for ferritin (0.78; 95% confidence interval [CI], 0.67–0.86), soluble transferrin receptor (sTfR; 0.79; 95% CI, 0.69–0.87), sTfR/ferritin ratio (0.74; 95% CI, 0.62–0.83), and hepcidin (0.89; 95% CI, 0.84–0.94). In a subset of 30 women, lower reliability was observed for serum iron (0.50; 95% CI, 0.29–0.70), unsaturated iron-binding capacity (0.55; 95% CI, 0.34–0.73), total iron-binding capacity (0.60; 95% CI, 0.40–0.76), and serum transferrin saturation rate (0.44; 95% CI, 0.22–0.65). The reliability of anti-5-hydroxymethyl-2′-deoxyuridine autoantibody titers, a biomarker of oxidized DNA damage, one of the mechanisms by which iron is thought to impact disease risk, was very high (0.97, 95% CI, 0.5–0.99). Conclusions Our results show that some newly developed iron-related assays could be useful tools to assess iron–disease associations in prospective cohorts that collect a single blood sample.

In 2001, a service dedicated to family planning was created within a large public hospital to improve patient care services. This retrospective chart review demonstrates the benefit of focusing these services in a specialty clinic.A power analysis was performed and determined that a minimum of 136 charts were needed in each arm of the study to determine if, following an elective abortion, there was a significant increase in attendance at the scheduled postoperative visit. Secondary variables included analysis of contraceptive choice, incidence of continuation of injectable contraception and incidence of repeat pregnancy.After counseling services were initiated, there was a 27% increase in the number of patients returning for the postoperative clinic appointment within 8 weeks [32% (61/191) in 1998 vs. 59% (80/136) in 2001; p.0001]. There was also a significant decrease in patients without a plan for contraception, 29% in 1998 vs. 11% in 2001, and a decrease in repeat pregnancies from 9% in 1998 to 1.5% in 2001. There was no difference in patient adherence with injectable contraception.Consolidation of abortion services improves subsequent use of contraception and reduces incidence of repeat pregnancy.

Objective We investigated whether levels of annexin A5 (AnxA5), AnxA5 anticoagulant activity and binding, and anti-AnxA5 antibodies might be altered in women with previous histories of recurrent spontaneous pregnancy losses (RSPL) when tested during pregnancy. Study design Ninety pregnant women with histories of 3 or more RSPL (cases) and 150 women without adverse pregnancy histories (controls) were assayed for these AnxA5 parameters. Results There were no significant differences between cases and controls in AnxA5 levels (median, 23.1 ng/mL [range, 2.1-201.1 ng/mL] vs 19.7 ng/mL [2.1-151.5 ng/mL]; P = .20), AnxA5 anticoagulant activity (183% [101%-236%] vs 168% [128%-256%]; P = .39) and binding (6.0 ng/aliquot PL [2.1-19.5 ng/aliquot PL) vs 6.1 ng/aliquot PL [1.6-16.8 ng/aliquot PL]; P = .72), and anti-AnxA5 antibody levels. Conclusions AnxA5 parameters do not distinguish between cases and controls when tested during pregnancy. The pregnant state itself appears to be associated with altered levels of AnxA5 parameters.

BACKGROUND: Black ethnicity is one of the risk factors for uterine leiomyomata (ULM). Little is known about the ethnic differences in leiomyoma-associated gene products in women with uterine leiomyomata. METHODS: A total of 120 hysterectomies with ULM were collected from black, Asian, Hispanic and white women (30 cases from each group). Twenty-two gene products were selected for the study. The expressions of the selected dysregulated gene products were measured by the semiquantification and the immunoscores were normalized by matched myometrium. RESULTS: The relative expressions of progesterone receptor A (PR-A) (up-regulation), retinoid acid receptor (down-regulation), and retinoid X receptor (RXR) (no change) in leiomyomata compared to normal myometrium in black women were significantly different compared to other ethnic groups (P < 0.05). About one-third of ULM from black women subclustered together in association with a group of up-regulated gene products. Many other gene products, including local growth factors, insulin-like growth factor (IGF)-signalling proteins, and cell proliferation markers, were dysregulated in ULM but showed non-significant differences between the ethnic groups. CONCLUSIONS: There are substantial differences of the sex steroid receptors and other nuclear receptors between black women and other ethnic groups. Based on tissue microarray data, there are at least two broad groups of leiomyomata presented by the dysregulation of different groups of gene products. One is dominated by up-regulation of amplified in breast cancer 1, CD24, hamartin, human mobility group gene 2, IGF2, PR-A and RXR, and the other is characterized by up-regulation of epithelial growth factor receptor, down-regulation of hamartin, PR-A and tuberin.

Circulating insulin-like growth factor-I (IGF-I) and its major binding protein IGF binding protein-3 (IGFBP-3) have been associated with increased risk of premenopausal breast cancer, although risk estimates varied broadly. An extension of a case-control study (138 cases, 259 matched controls) on IGF-I and breast cancer in premenopausal women nested in the New York University Women's Health Study cohort offered the opportunity to address the hypothesis that such variability may have been the result of variations in the ability of different IGFBP-3 assays to specifically measure intact/functional forms of the protein. IGF-I and IGFBP-3 had originally been measured using in-house RIAs. These measurements were repeated using commercially available ELISAs [Diagnostic System Laboratories (DSL), Webster, Texas], and a third ELISA with greater specificity for active forms for IGFBP-3. Pearson's correlations between IGF-I concentrations in the original study and DSL ELISA were very high [r = 0.92; 95% CI, 0.90-0.94]. Correlations with DSL ELISA were much lower for IGFBP-3 (r = 0.58; 0.49-0.66) and even lower still with the assay for functional IGFBP-3 (r = 0.33; 0.20-0.44). IGF-I and IGFBP-3 measurements by the DSL ELISA methods showed statistically significant relationships with risk. The odds ratios (OR) for top versus bottom quartiles were 1.93 (1.00-3.72; P = 0.02) and 2.03 (1.09-3.76; P = 0.02), respectively, in agreement with the original observations. In contrast, measurements of functional IGFBP-3 tended to be unrelated to risk [ORs for the top versus bottom quartile, 0.97 (0.44-2.11)]. The association with IGF-I became substantially weaker and lost statistical significance after adjustment for IGFBP-3 using DSL ELISA, but became considerably stronger when adjusting for the functional IGFBP-3 measurements [OR = 2.43 (1.21-4.90); P = 0.005], or when considering the molar ratio of IGF-I to IGFBP-3 [OR = 2.37 (1.13-5.00); P = 0.02]. These results are consistent with an association of breast cancer risk in young women with elevated IGF-I and IGFBP-3, and show that for IGFBP-3, the strength of such an association could vary substantially depending on the assay used.