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Harris H.,Karolinska Institutet | Harris H.,Obstetrics and Gynecology Epidemiology Center | Harris H.,Fred Hutchinson Cancer Research Center | Wolk A.,Karolinska Institutet | And 4 more authors.
International Journal of Molecular Epidemiology and Genetics | Year: 2016

Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between sVEGFR2 and 3 levels and breast cancer risk. The analysis included 69 incident breast cancer cases diagnosed after blood collection and 719 controls. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. After adjustment for breast cancer risk factors, sVEGFR2 levels were associated with breast cancer risk (OR=1.28; 95% CI=1.06-1.56 per 1000 ng/L increase in concentration) while sVEGFR3 levels were not related to such risk (OR=1.00; 95% CI=0.93-1.07). Our results suggest that sVEGFR2 levels may be positively associated with breast cancer risk, however future studies with larger case groups are necessary to confirm this association. © 2016, E-Century Publishing Corporation. All rights reserved.

Shivappa N.,University of South Carolina | Harris H.,Karolinska Institutet | Harris H.,Obstetrics and Gynecology Epidemiology Center | Wolk A.,Karolinska Institutet | Hebert J.R.,University of South Carolina
European Journal of Nutrition | Year: 2016

Purpose: Diet and dietary components have been studied previously in relation to mortality; however, little is known about the relationship between the inflammatory potential of overall diet and mortality. Materials and methods: We examined the association between the Dietary Inflammatory Index (DII) and mortality among 33,747 participants in the population-based Swedish Mammography Cohort. The DII score was calculated based on dietary information obtained from a self-administered food frequency questionnaire. Mortality was determined through linkage to the Swedish Cause of Death Registry through 2013. Cox proportional hazard regression was used to estimate hazard ratios (HR). During 15 years of follow-up, 7095 deaths were identified, including 1996 due to cancer, 602 of which were due to digestive-tract cancer, and 2399 due to cardiovascular disease. Results: After adjusting for age, energy intake, education, alcohol intake, physical activity, BMI, and smoking status, analyses revealed a positive association between higher DII score and all-cause mortality. When used as a continuous variable (range −4.19 to 5.10), DII score was associated with all-cause mortality (HRContinuous = 1.05; 95 % CI 1.01–1.09) and digestive-tract cancer mortality (HRContinuous = 1.15; 95 % CI 1.02–1.29). Comparing subjects in the highest quintile of DII (≥1.91) versus the lowest quintile (DII ≤ −0.67), a significant association was observed for all-cause mortality (HR = 1.25; 95 % CI 1.07–1.47, Ptrend = 0.003). Conclusion: These results indicate that a pro-inflammatory diet, as indicated by higher DII score, was associated with all-cause and digestive-tract cancer mortality. © 2015, Springer-Verlag Berlin Heidelberg.

Weizman N.F.,Brigham and Womens Hospital | Einarsson J.I.,Brigham and Womens Hospital | Wang K.C.,Brigham and Womens Hospital | Vitonis A.F.,Obstetrics and Gynecology Epidemiology Center | Cohen S.L.,Brigham and Womens Hospital
Journal of the Society of Laparoendoscopic Surgeons | Year: 2015

Background and Objectives: To evaluate whether the route and surgical technique by which hysterectomy is performed influence the incidence of vaginal cuff dehiscence. Methods: We performed a retrospective analysis of total hysterectomy cases performed at Brigham and Woman’s Hospital or Faulkner Hospital during 2009 through 2011. Results: During the study period, 2382 total hysterectomies were performed; 23 of these (0.96%) were diagnosed with cuff dehiscence, and 4 women had recurrent dehiscence. Both laparoscopic (odds ratio, 23.4; P =.007) and robotic (odds ratio, 73; P =.0006) hysterectomies were associated with increased odds of cuff dehiscence in a multivariate regression analysis. The type of energy used during colpotomy, mode of closure (hand sewn, laparoscopic suturing, or suturing assisted by a device), and suture material did not differ significantly between groups; however, continuous suturing of the cuff was a protective factor (odds ratio, 0.24; P =.03). Women with dehiscence had more extensive procedures, as well as an increased incidence of additional major postoperative complications (17.4% vs 3%, P =.004). Conclusion: The rate of cuff dehiscence in our cohort correlates with the current literature. This study suggests that the risk of dehiscence is influenced mainly by the scope and complexity of the surgical procedure. It seems that different colpotomy techniques do not influence the rate of cuff dehiscence; however, continuous suturing of the cuff may be superior to interrupted suturing. © 2015 by JSLS, Journal of the Society of Laparoendoscopic Surgeons.

Cuellar-Partida G.,QIMR Berghofer Medical Research Institute | Cuellar-Partida G.,University of Queensland | Lu Y.,QIMR Berghofer Medical Research Institute | Dixon S.C.,QIMR Berghofer Medical Research Institute | And 119 more authors.
Human Genetics | Year: 2016

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ((Formula presented.) = 8.8 ± 1.1 %), endometrioid ((Formula presented.) = 3.2 ± 1.6 %), clear cell ((Formula presented.) = 6.7 ± 3.3 %) and all EOC ((Formula presented.) = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach. © 2016 Springer-Verlag Berlin Heidelberg

Michels K.B.,Obstetrics and Gynecology Epidemiology Center
Obstetrics and Gynecology | Year: 2010

Objective: To estimate the association between maternal pregnancy-related hypertension and offspring hypertension later in life in a birth cohort from New England. Methods: Covariate and exposure data were collected between 1959 and 1966 through the Collaborative Perinatal Project. Follow-up information was obtained through the New England Family Study between 2001 and 2004, when study participants were between 34 and 44 years old. The study population consisted of 1,556 individuals. Participants who reported having hypertension diagnosed at least once were considered to have hypertension. Logistic regression was used to estimate the association between maternal pregnancy-related hypertension and offspring hypertension later in life. Results were adjusted for sex, maternal race, maternal body mass index, maternal socioeconomic status, maternal diabetes, and twin pregnancy. Results: Maternal pregnancy-related hypertension was associated with an increased risk of being prescribed antihypertensives compared with never having hypertension diagnosed (from 8.8% to 17.4%; adjusted odds ratio 1.88, 95% confidence interval 1.00-3.55). The association was not attenuated after adjustment for birth weight or preterm delivery. After excluding offspring of women who reported hypertension during pregnancy only, this association increased to an adjusted odds ratio of 1.97 (95% confidence interval 1.04-3.72). Conclusion: In a birth cohort from New England, maternal pregnancy-related hypertension was associated with hypertension in offspring later in life. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams and Wilkins.

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