Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium.

BACKGROUND: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. METHODS: We analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. RESULTS: Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100 mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500 mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). CONCLUSIONS: Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.

Consumption of sugary foods and drinks and risk of endometrial cancer.

Consumption of foods high in sugar promotes insulin production, which has been linked to endometrial carcinogenesis. We evaluated the impact of dietary intake of sugary foods and beverages, as well as added sugar and total sugar on endometrial cancer risk in a population-based case-control study, including 424 cases and 398 controls. Participants completed an interview and food frequency questionnaire, and provided self-recorded waist and hip measurements. Women in the highest quartile of added sugar intake had significantly increased endometrial cancer risk (OR = 1.84, 95% CI 1.16-2.92). Among women with waist-to-hip ratio ≥0.85, risk was significantly higher for the highest versus lowest tertile of added sugar intakes (OR = 2.50, 95% CI 1.38-4.52). The association with added sugar also became stronger when analyses were restricted to never users of hormone replacement therapy (OR = 2.03; 95% CI 1.27-3.26, for highest versus lowest tertile). There was little evidence of effect modification by body mass index or physical activity. Given the high prevalence of intake of sugary foods and drinks in Western populations, additional research is warranted to confirm our findings on endometrial cancer.

Tubal ligation and risk of ovarian cancer subtypes: a pooled analysis of case-control studies.

BACKGROUND: Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes. METHODS: We pooled primary data from 13 population-based case-control studies, including 10,157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13,904 control women. Invasive cases were analysed by histological type, grade and stage, and borderline cases were analysed by histological type. Pooled odds ratios were estimated using conditional logistic regression to match on site, race/ethnicity and age categories, and to adjust for age, oral contraceptive use duration and number of full-term births. RESULTS: Tubal ligation was associated with significantly reduced risks of invasive serous (OR, 0.81; 95% CI, 0.74-0.89; P < 0.001), endometrioid (OR, 0.48; 95% CI, 0.40-0.59; P < 0.001), clear cell (OR, 0.52; 95% CI, 0.40-0.67; P < 0.001) and mucinous (OR, 0.68; 95% CI, 0.52-0.89; P = 0.005) cancers. The magnitude of risk reduction was significantly greater for invasive endometrioid (P < 0.0001) and clear cell (P = 0.0018) than for serous cancer. No significant associations were found with borderline serous or mucinous tumours. CONCLUSIONS: We found that the protective effects of tubal ligation on ovarian cancer risk were subtype-specific. These findings provide insights into distinct aetiologies of ovarian cancer subtypes and mechanisms underlying the protective effects of tubal ligation.

Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies.

PURPOSE: The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. METHODS: We used data from 21 case-control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. RESULTS: Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03-1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39-2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12-1.50). For these histological types, consistent dose-response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. CONCLUSIONS: Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease.

Sugary food and beverage consumption and epithelial ovarian cancer risk: a population-based case-control study.

BACKGROUND: Ovarian cancer is the deadliest gynecologic cancer in the US. The consumption of refined sugars has increased dramatically over the past few decades, accounting for almost 15% of total energy intake. Yet, there is limited evidence on how sugar consumption affects ovarian cancer risk. METHODS: We evaluated ovarian cancer risk in relation to sugary foods and beverages, and total and added sugar intakes in a population-based case-control study. Cases were women with newly diagnosed epithelial ovarian cancer, older than 21 years, able to speak English or Spanish, and residents of six counties in New Jersey. Controls met same criteria as cases, but were ineligible if they had both ovaries removed. A total of 205 cases and 390 controls completed a phone interview, food frequency questionnaire, and self-recorded waist and hip measurements. Based on dietary data, we computed the number of servings of dessert foods, non-dessert foods, sugary drinks and total sugary foods and drinks for each participant. Total and added sugar intakes (grams/day) were also calculated. Multiple logistic regression models were used to estimate odds ratios and 95% confidence intervals for food and drink groups and total and added sugar intakes, while adjusting for major risk factors. RESULTS: We did not find evidence of an association between consumption of sugary foods and beverages and risk, although there was a suggestion of increased risk associated with sugary drink intake (servings per 1,000 kcal; OR=1.63, 95% CI: 0.94-2.83). CONCLUSIONS: Overall, we found little indication that sugar intake played a major role on ovarian cancer development.

Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium.

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case-control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m(2); 95% CI 1.18-1.30), invasive endometrioid (1.17; 1.11-1.23) and invasive mucinous (1.19; 1.06-1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94-1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03-1.25) and in pre-menopausal women (1.11; 1.04-1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium.

BACKGROUND: Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations. METHODS: We pooled data from 12 case-control studies in the Ovarian Cancer Association Consortium comprising 5,342 OC cases, 1,455 borderline tumors and 10,358 controls with quantitative information on recent alcohol intake to estimate odds ratios (OR) and 95% confidence intervals (CI) according to frequencies of average daily intakes of beer, wine, liquor and total alcohol. RESULTS: Total alcohol intake was not associated with all OC: consumption of >3 drinks per day compared to none, OR=0.92, 95% CI=0.76-1.10, P trend=0.27. Among beverage types, a statistically non-significant decreased risk was observed among women who consumed >8 oz/d of wine compared to none (OR=0.83, 95% CI=0.68-1.01, P trend=0.08). This association was more apparent among women with clear cell OC (OR, 0.43; 95% CI, 0.22-0.83; P trend=0.02), although based on only 10 cases and not statistically different from the other histologic types (P value for statistical heterogeneity between histologic types = 0.09). Statistical heterogeneity of the alcohol- and wine-OC associations was seen among three European studies, but not among eight North American studies. No statistically significant associations were observed in separate analyses evaluating risk with borderline tumors of serous or mucinous histology. Smoking status did not significantly modify any of the associations. CONCLUSIONS: We found no evidence that recent moderate alcohol drinking is associated with increased risk for overall OC, or that variation in risk is associated strongly with specific histologic types. Understanding modifiable causes of these elusive and deadly cancers remains a priority for the research community.

Total and individual antioxidant intake and risk of epithelial ovarian cancer.

BACKGROUND: Limiting oxidative stress to the ovarian epithelium has been proposed as a first-line defense against ovarian cancer. Although evidence for an association between individual dietary antioxidant intake and ovarian cancer risk is conflicting, the combined evidence suggests a modest inverse association. Our study aimed to evaluate the association between total antioxidant capacity (TAC) and individual antioxidant intakes (vitamin C, vitamin E, beta-carotene, selenium, lutein, and lycopene) and ovarian cancer risk. METHODS: We conducted a population-based case-control study in New Jersey. Cases were women ages 21 years and older with newly diagnosed epithelial ovarian cancer who resided in six counties of New Jersey. Controls were women in the same age range who resided in the same geographic area. A total of 205 ovarian cancer cases and 390 controls were included. Dietary intake was ascertained using the Block food frequency questionnaire (FFQ), and TAC indices were constructed by linking FFQ-derived estimates to two standardized antioxidant capacity databases, the USDA Oxygen Radical Absorbance Capacity (ORAC) Database, and the University of Olso's Antioxidant Food Database. Multivariate logistic regression models were used to calculate odds ratios and 95 % confidence intervals while controlling for major ovarian cancer risk factors. RESULTS: We found a strong inverse association with selenium from food sources (OR: 0.41; 95 % CI: 0.20-0.85, for the highest vs. lowest tertile of dietary selenium intake). However, there was little evidence of an association with dietary TAC or the others individual antioxidants. In contrast, compared to non-users, supplement users had significant increased risk for all micronutrients, but no statistically significant increased risk was observed for combined intake from foods and supplements of any of these antioxidants. CONCLUSIONS: This study found an inverse association between selenium consumption from food sources and ovarian cancer risk, while there was little evidence of an association with TAC or any of the other individual antioxidants. Additional research is needed to confirm these findings.

Urinary mycoestrogens, body size and breast development in New Jersey girls.

BACKGROUND: Despite extensive research and interest in endocrine disruptors, there are essentially no epidemiologic studies of estrogenic mycotoxins, such as zeranol and zearalenone (ZEA). ZEA mycoestrogens are present in grains and other plant foods through fungal contamination, and in animal products (e.g., meat, eggs, dairy products) through deliberate introduction of zeranol into livestock to enhance meat production, or by indirect contamination of animals through consumption of contaminated feedstuff. Zeranol is banned for use in animal husbandry in the European Union and other countries, but is still widely used in the US. Surprisingly, little is known about the health effects of these mycoestrogens, including their impact on puberty in girls, a period highly sensitive to estrogenic stimulation. OBJECTIVES AND METHODS: We conducted a cross-sectional analysis among 163 girls, aged 9 and 10 years, participating in the Jersey Girl Study to measure urinary mycoestrogens and their possible relationship to body size and development. RESULTS: We found that mycoestrogens were detectable in urine in 78.5% of the girls, and that urinary levels were predominantly associated with beef and popcorn intake. Furthermore, girls with detectable urinary ZEA mycoestrogen levels tended to be shorter and less likely to have reached the onset of breast development. CONCLUSIONS: Our findings suggest that ZEA mycoestrogens may exert anti-estrogenic effects similar to those reported for isoflavones. To our knowledge, this was the first evaluation of urinary mycoestrogens and their potential health effects in healthy girls. However, our findings need replication in larger studies with more heterogeneous populations, using a longitudinal approach.

Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study.

BACKGROUND: While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention. METHODS: We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol. RESULTS: No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little evidence of an inverse association for isoflavones, lignans, or coumestrol. CONCLUSIONS: This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance.

Healthy eating index and ovarian cancer risk.

The evidence for a role of diet on ovarian cancer prevention remains inconclusive. While many studies have evaluated individual foods and food groups, the evaluation of a comprehensive dietary quality index for predicting cancer risk has received little attention. This study investigates the association between the Healthy Eating Index (HEI), which reflects adherence to the current USDA Dietary Guidelines for Americans and ovarian cancer risk in a population-based case-control study in New Jersey. A total of 205 cases and 390 controls completed the Block 98.2 food frequency questionnaire (FFQ) in addition to reporting on potential risk factors for ovarian cancer. FFQ data were then utilized to calculate the HEI score, and cup, ounce, gram, or caloric equivalents for the 12 different food groups comprising the index. In multivariate models, the OR for the highest tertile of the HEI score compared with the lowest (reflecting a better diet compared with a worse diet) was 0.90 (95% CI: 0.55-1.47). There was limited evidence for a statistically significant association between any of the 12 individual food components and ovarian cancer risk. Based on this study's results, neither individual food groups nor dietary quality showed potential for preventing ovarian cancer.

Adherence to the dietary guidelines for Americans and endometrial cancer risk.

The Healthy Eating Index (HEI) was developed by the US Department of Agriculture with the goal of quantifying adherence to the Dietary Guidelines for Americans. The purpose of this study was to evaluate the impact of the HEI-2005 score and each of its components on endometrial cancer risk in a population-based case-control study in New Jersey. A total of 424 cases and 398 controls completed a Food Frequency Questionnaire, which was used to derive the HEI-2005 score. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression while adjusting for potential covariates, which included all major endometrial cancer risk factors. The adjusted OR for women in the highest quartile when compared to the lowest quartile was 0.83 (95% CI: 0.52-1.34). For the meat and beans component comprising meat, eggs, poultry, fish, and beans, the OR was 0.70 (95% CI: 0.45-1.11; p for trend: 0.07), with little evidence of an association with any of the individual foods. There was no indication of an association for any of the other components of the HEI or of effect modification by body mass index. This study suggested limited value for the HEI-2005 in predicting endometrial cancer risk.

Coffee and tea consumption and endometrial cancer risk in a population-based study in New Jersey.

We evaluated the role of tea and coffee and substances added (sugar/honey, creamers, and milk) on endometrial cancer risk in a population-based case-control study in six counties in New Jersey, including 417 cases and 395 controls. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression. There was a moderate inverse association with coffee consumption, with an adjusted OR of 0.65 (95% CI: 0.36-1.17) for women who reported more than two cups/day of coffee compared to none. Tea consumption appeared to increase risk (OR: 1.93; 95% CI: 1.08-3.45), but after including the variables sugar/honey and cream/milk added to tea in the model, the risk estimate was attenuated and no longer statistically significant (OR: 1.77; 95% CI: 0.96-3.28 for those consuming more than one cup/day of tea compared to nonusers). There was a suggestion of a decreased risk associated with green tea, but the confidence interval included one (adjusted OR for one or more cups/week vs. none: 0.75; 95% CI: 0.48-1.18). We found an association with adding sugar/honey to tea, with those adding two or more teaspoons/cup having an OR of 2.66 (95% CI: 1.42-4.98; p for trend <0.01) after adjusting for relevant confounders. For sugar/honey added to coffee the corresponding OR was 1.43 (95% CI: 0.81-2.55). Our results indicate that sugars and milk/cream added to coffee and tea should be considered in future studies evaluating coffee and tea and endometrial cancer risk.