Megan S. Rice

Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis

PurposeThe purpose of this meta-analysis was to determine the strength of the association between gynecologic surgeries, tubal ligation and hysterectomy, and ovarian cancer.MethodsWe searched the PubMed, Web of Science, and Embase databases for all English-language articles dated between 1969 through March 2011 using the keywords “ovarian cancer” and “tubal ligation” or “tubal sterilization” or “hysterectomy.” We identified 30 studies on tubal ligation and 24 studies on hysterectomy that provided relative risks for ovarian cancer and a p-value or 95% confidence interval (CI) to include in the meta-analysis. Summary RRs and 95% CIs were calculated using a random-effects model.ResultsThe summary RR for women with vs. without tubal ligation was 0.70 (95%CI: 0.64, 0.75). Similarly, the summary RR for women with vs. without hysterectomy was 0.74 (95%CI: 0.65, 0.84). Simple hysterectomy and hysterectomy with unilateral oophorectomy were associated with a similar decrease in risk (summery RR = 0.62, 95%CI: 0.49-0.79 and 0.60, 95%CI: 0.47-0.78, respectively). In secondary analyses, the association between tubal ligation and ovarian cancer risk was stronger for endometrioid tumors (summary RR = 0.45, 95%CI: 0.33, 0.61) compared to serous tumors.ConclusionObservational epidemiologic evidence strongly supports that tubal ligation and hysterectomy are associated with a decrease in the risk of ovarian cancer, by approximately 26-30%. Additional research is needed to determine whether the association between tubal ligation and hysterectomy on ovarian cancer risk differs by individual, surgical, and tumor characteristics.

Habitual Coffee Consumption and Risk of Heart Failure: A Dose-Response Meta-Analysis

Background— There have been discrepant findings on the association between coffee consumption and risk of incident heart failure. Methods and Results— We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure. We searched electronic databases (MEDLINE, Embase, and CINAHL) from January 1966 through December 2011, with the use of a standardized protocol. Eligible studies were prospective cohort studies that examined the association of coffee consumption with incident heart failure. Five independent prospective studies of coffee consumption and heart failure risk, including 6522 heart failure events and 140 220 participants, were included in the meta-analysis. We observed a statistically significant J-shaped relationship between coffee and heart failure. Compared with no consumption, the strongest inverse association was seen for 4 servings/day and a potentially higher risk at higher levels of consumption. There was no evidence that the relationship between coffee and heart failure risk varied by sex or by baseline history of myocardial infarction or diabetes. Conclusions— Moderate coffee consumption is inversely associated with risk of heart failure, with the largest inverse association observed for consumption of 4 servings per day.Background—There have been discrepant findings on the association between coffee consumption and risk of incident heart failure. Methods and Results—We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure. We searched electronic databases (MEDLINE, Embase, and CINAHL) from January 1966 through December 2011, with the use of a standardized protocol. Eligible studies were prospective cohort studies that examined the association of coffee consumption with incident heart failure. Five independent prospective studies of coffee consumption and heart failure risk, including 6522 heart failure events and 140 220 participants, were included in the meta-analysis. We observed a statistically significant J-shaped relationship between coffee and heart failure. Compared with no consumption, the strongest inverse association was seen for 4 servings/day and a potentially higher risk at higher levels of consumption. There was no evidence that the relationship between coffee and heart failure risk varied by sex or by baseline history of myocardial infarction or diabetes. Conclusions—Moderate coffee consumption is inversely associated with risk of heart failure, with the largest inverse association observed for consumption of 4 servings per day.

Intake of dietary flavonoids and risk of epithelial ovarian cancer

Background: The impact of different dietary flavonoid subclasses on risk of epithelial ovarian cancer is unclear, with limited previous studies that have focused on only a few compounds. Objective: We prospectively examined associations between habitual flavonoid subclass intake and risk of ovarian cancer. Design: We followed 171,940 Nurses’ Health Study and Nurses’ Health Study II participants to examine associations between intakes of total flavonoids and their subclasses (flavanones, flavonols, anthocyanins, flavan-3-ols, flavones, and polymeric flavonoids) and risk of ovarian cancer by using Cox proportional hazards models. Intake was calculated from validated food-frequency questionnaires collected every 4 y. Results: During 16–22 y of follow-up, 723 cases of ovarian cancer were confirmed through medical records. In pooled multivariate-adjusted analyses, total flavonoids were not statistically significantly associated with ovarian cancer risk (HR for the top compared with the bottom quintile: 0.85; 95% CI: 0.66, 1.09; P-trend = 0.17). However, participants in the highest quintiles of flavonol and flavanone intakes had modestly lower risk of ovarian cancer than did participants in the lowest quintile, although the P-trend was not significant [HRs: 0.76 (95% CI: 0.59, 0.98; P-trend = 0.11) and 0.79 (95% CI: 0.63,1.00; P-trend = 0.26), respectively]. The association for flavanone intake was stronger for serous invasive and poorly differentiated tumors (comparable HR: 0.68; 95% CI: 0.50, 0.92; P-heterogeneity = 0.10, P-trend = 0.07) compared with nonserous and less-aggressive tumors. Intakes of other subclasses were not significantly associated with risk. In food-based analyses used to compare subjects who consumed >1 and ≤1 cup black tea/d, the HR was 0.68 (95% CI: 0.51, 0.90; P < 0.01). Conclusions: Higher intakes of flavonols and flavanones as well as black tea consumption may be associated with lower risk of ovarian cancer. Additional prospective studies are required to confirm these findings.

Tubal ligation, hysterectomy, and epithelial ovarian cancer in the New England Case-Control Study

Previous studies have observed that tubal ligation and hysterectomy are associated with a decreased risk of ovarian cancer; however, little is known about whether these associations vary by surgical characteristics, individual characteristics or tumor histology. We used logistic regression to examine tubal ligation, simple hysterectomy and hysterectomy with unilateral oophorectomy in relation to risk of epithelial ovarian cancer in the New England Case–Control Study. Our primary analysis included 2,265 cases and 2,333 controls. Overall, tubal ligation was associated with a lower risk of epithelial ovarian cancer [odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.68–0.97], especially for endometrioid tumors (OR = 0.45, 95% CI: 0.29–0.69). The inverse association between tubal ligation and ovarian cancer risk was stronger for women who had undergone the procedure at the time of last delivery (OR = 0.60, 95% CI: 0.42–0.84) rather than at a later time (OR = 0.93, 95% CI: 0.75–1.15). Overall, simple hysterectomy was not associated with ovarian cancer risk (OR: 1.09, 95% CI: 0.83–1.42), although it was associated with a nonsignificant decreased risk of ovarian cancer among women who underwent the procedure at age 45 or older (RR: 0.64, 95% CI: 0.40–1.02) or within the last 10 years (OR = 0.65, 95% CI: 0.38–1.13). Overall, women who had a hysterectomy with a unilateral oophorectomy had significantly lower risk of ovarian cancer (OR = 0.65, 95% CI: 0.45–0.94). In summary, tubal ligation and hysterectomy with unilateral oophorectomy were inversely associated with ovarian cancer risk in a large population‐based case–control study. Additional research is necessary to understand the potential biologic mechanisms by which these procedures may reduce ovarian cancer risk.

Metabolic Syndrome and Mammographic Density in Mexican Women

Metabolic syndrome has been associated with an increased risk of breast cancer; however, little is known about the association between metabolic syndrome and percent mammographic density, a strong predictor of breast cancer. We analyzed cross-sectional data from 789 premenopausal and 322 postmenopausal women in the Mexican Teachers Cohort (ESMaestras). Metabolic syndrome was defined according to the harmonized definition. We measured percent density on mammograms using a computer-assisted thresholding method. Multivariable linear regression was used to estimate the association between density and metabolic syndrome, as well as its components by state (Jalisco, Veracruz) and menopausal status (premenopausal, postmenopausal). Among premenopausal women in Jalisco, women with metabolic syndrome had higher percent density than those without after adjusting for potential confounders including BMI [difference = 4.76; 95% confidence interval (CI), 1.72–7.81]. Among the metabolic syndrome components, only low high-density lipoprotein levels (<50 mg/dL) were associated with significantly higher percent density among premenopausal women in Jalisco (difference = 4.62; 95% CI, 1.73–7.52). Metabolic syndrome was not associated with percent density among premenopausal women in Veracruz (difference = −2.91; 95% CI, −7.19 to 1.38), nor among postmenopausal women in either state. Metabolic syndrome was associated with higher percent density among premenopausal women in Jalisco, Mexico, but was not associated with percent density among premenopausal women in Veracruz, Mexico, or among postmenopausal women in either Jalisco or Veracruz. These findings provide some support for a possible role of metabolic syndrome in mammographic density among premenopausal women; however, results were inconsistent across states and require further confirmation in larger studies. Cancer Prev Res; 6(7); 701–10. ©2013 AACR.

Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

Background Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. Methods and findings We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35–85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (–0.46 cm [95% CI: −0.53, −0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was −0.24 cm (95% CI: −0.34, −0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (−0.38 cm [95% CI: −0.44, −0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. Conclusions Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

International Consortium on Mammographic Density: Methodology and population diversity captured across 22 countries.

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses.

Circulating concentrations of insulin-like growth factor-I, insulin-like growth factor-binding protein-3, genetic polymorphisms and mammographic density in premenopausal Mexican women: results from the ESMaestras cohort.

The insulin‐like growth factor (IGF) axis plays an essential role in the development of the mammary gland. High circulating levels of IGF‐I and of its major binding protein IGFBP3 have been related with increased mammographic density in Caucasian premenopausal women. Some common single nucleotide polymorphisms (SNPs) in genes of the IGF pathway have also been suggested to play a role in mammographic density. We conducted a cross‐sectional study nested within the large Mexican ESMaestras cohort to investigate the relation between circulating levels of IGF‐I, IGFBP‐3, the IGF‐I/IGFBP‐3 ratio, five common SNPs in the IGF‐1, IGFBP‐3 and IGF‐1R genes and mammographic density in 593 premenopausal Mexican women. Mean age at mammogram was 43.1 (standard deviation, SD = 3.7) years, and average body mass index (BMI) at recruitment was 28.5 kg/m2. Mean percent mammographic density was 36.5% (SD: 17.1), with mean dense tissue area of 48.3 (SD: 33.3) cm2. Mean IGF‐I and IGFBP‐3 concentrations were 15.33 (SD: 5.52) nmol/l and 114.96 (SD: 21.34) nmol/l, respectively. No significant associations were seen between percent density and biomarker concentrations, but women with higher IGF‐I and IGF‐I/IGFBP‐3 concentrations had lower absolute dense (ptrend = 0.03 and 0.09, respectively) and nondense tissue areas (ptrend < 0.001 for both parameters). However, these associations were null after adjustment by BMI. SNPs in specific genes were associated with circulating levels of growth factors, but not with mammographic density features. These results do not support the hypothesis of a strong association between circulating levels of growth hormones and mammographic density in Mexican premenopausal women.

Risk factors for chronic hepatitis B virus infection among blood donors in Bangalore, India.

Objectives and Aim: We performed a study of hepatitis B virus (HBV) risk factors among blood donors in Bangalore, India.

Salpingectomy as a Potential Ovarian Cancer Risk-Reducing Procedure

Accumulated evidence over the past 10 years has strongly indicated that the fallopian tube is the site of origin for many high-grade serous carcinomas (1), which represent 50% to 60% of all epithelial ovarian cancers. This multi-origin model of ovarian cancer development has important implications for prevention of ovarian cancer: if some or all high-grade serous tumors develop in the fallopian tube, then bilateral salpingectomy could prevent this most aggressive form of ovarian cancer. However, to date, no large-scale data regarding the impact of salpingec-tomy on ovarian cancer incidence have been available. The article by Falconer et al. (2) is the first to address this question. This study combined data from several population registries in Sweden to compare incidence of ovarian cancer in women with a previous gynecologic procedure for benign indications (salpingectomy, tubal ligation, total abdominal hysterectomy with bilateral salpingo-oophorectomy [BSO], and hysterectomy without concomitant bilateral salpingo-oophorectomy [TAH]) to women with no history of these surgeries. They reported a statistically significant 35% lower risk of ovarian cancer among women with a previous salpingectomy compared with women with no previous surgeries. Consistent with previous studies, all other gynecologic surgeries evaluated in this study were associated with lower ovarian cancer risk, ranging from a 21% lower risk associated with TAH to a 94% lower risk with BSO. It is well established that BSO almost entirely eliminates the risk of ovarian cancer; BSO is commonly used as an ovarian cancer risk-reducing measure in women with inherited BRCA mutations. However, BSO is not without side effects. First, in young women, this surgery results in early menopause, which is associated with increased risk of cardiovascular diseases, neuro-logical diseases, psychiatric diseases, osteoporosis, and overall mortality (3). Further, studies have demonstrated that post-menopausal women with BSO compared with TAH alone have increased overall mortality and increased risks of cardiovascular and neurologic diseases (4). Therefore, given the risks associated with BSO compared with the low lifetime risk of ovarian cancer in women without BRCA mutations (1 in 72), BSO is not recommended on a population level for prevention of ovarian cancer. The finding that many high-grade serous ovarian cancers arise in the fallopian tube has thus prompted the question: Could sal-pingectomy be a safer, but still effective, alternative to BSO for ovarian cancer prevention? The results provided in the Swedish study suggest that salpingectomy may reduce the risk of ovarian cancer, but to a lesser degree than …