Person:

Terry, Kathryn

Background: Several dietary indices have been developed to measure overall diet quality, including the Healthy Eating Index-2005 (HEI-2005), which measures adherence to the 2005 Dietary Guidelines from the USDA; the Alternative Healthy Eating Index-2010 (AHEI-2010), which is based on foods and nutrients predictive of chronic disease risk; and the Alternate Mediterranean Diet Score (aMDS), which is an index that characterizes traditional food patterns of Mediterranean countries. Few studies have evaluated diet quality and ovarian cancer risk. Methods: We assessed the associations of the HEI-2005, AHEI-2010, and aMDS with risk of epithelial ovarian cancer prospectively among women in the Nurses’ Health Study. We used Cox proportional hazards models, adjusting for known ovarian cancer risk factors. Results: During 24 years of follow-up, we documented 696 incident epithelial ovarian cancer cases among 82,948 women with diet information. The multivariate adjusted hazard ratios (95% confidence interval; Ptrend) of epithelial ovarian cancer comparing the highest with the lowest quintile were 1.03 (0.80-1.34; 0.77) for the AHEI-2010, 0.85 (0.65-1.12; 0.57) for the HEI-2005, and 0.91 (0.71-1.18; 0.44) for the aMDS. Conclusions: We did not observe any clear association of three diet quality scores with ovarian cancer risk. Further work should other metrics of evaluating diet quality that may be more relevant cancer risk. Electronic supplementary material The online version of this article (doi:10.1186/s13048-014-0112-4) contains supplementary material, which is available to authorized users.

Objective: To examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival. Methods: We genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models. Results: Cases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset. Conclusion: This targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted.

Background: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening. Methods: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression. Results: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination. Conclusions: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors. Electronic supplementary material The online version of this article (doi:10.1186/s13048-017-0315-6) contains supplementary material, which is available to authorized users.

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4–21% in reproductive aged women. The altered metabolic and hormonal environment among women with PCOS may increase their risk of some types of cancer. Methods: We performed a comprehensive review of the literature using numerous search terms for all studies examining the associations between polycystic ovary syndrome and related characteristics and cancer published in English through October 2016. This review summarizes the epidemiological findings on the associations between PCOS and endometrial, ovarian, and breast cancers and discusses the methodological issues, complexities, and underlying mechanisms of these associations. Results: We identified 11 individual studies and 3 meta-analyses on the associations between PCOS and endometrial cancer, 8 studies and 1 meta-analysis for ovarian cancer, and 10 studies and 1 meta-analysis for breast cancer. Multiple studies reported that women with PCOS were at a higher risk for endometrial cancer; however, many did not take into account body mass index (BMI), a strong and well-established risk factor for endometrial cancer. The association with ovarian cancer was less clear, but a potentially increased risk of the borderline serous subtype was reported by two studies. No consistent association between PCOS risk and breast cancer was observed. Conclusion: The associations between PCOS and endometrial, ovarian, and breast cancer are complex, with the need to consider many methodological issues in future analyses. Larger well-designed studies, or pooled analyses, may help clarify these complex associations.

Telomeres are repetitive non-coding DNA sequences at the ends of chromosomes that provide protection against chromosomal instability. Telomere length and stability are influenced by proteins, including telomerase which is partially encoded by the TERT gene. Genetic variation in the TERT gene is associated with ovarian cancer risk, and predicts survival in lung cancer and glioma. We investigated whether genetic variation in five telomere maintenance genes was associated with survival among 1480 cases of invasive epithelial ovarian cancer in the population-based New England Case-Control Study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals. Overall we observed no significant associations between SNPs in telomere maintenance genes and mortality using a significance threshold of p=0.001. However, we observed some suggestive associations in subgroup analyses. Future studies with larger populations may further our understanding of what role telomeres play in ovarian cancer survival.

Conflicting reports regarding the relationship between breast-feeding and ovarian cancer risk suggest a possible influence of patterns of breast-feeding. We used logistic regression to examine breast-feeding in a large population of parous women who participated in a case–control study of ovarian cancer in New Hampshire and MA, USA. Risk of ovarian cancer was reduced in parous women who ever breast-fed (OR: 0.75; 95% CI: 0.62, 0.92), but evidence was limited for an influence of duration of breast-feeding and the number of children breast-fed. Compared to never breast-feeding, inverse associations were seen for breast-feeding all children (OR: 0.72; 95% CI: 0.58, 0.91) and for breast-feeding some children when the last born child was breast-fed (OR: 0.58; 95% CI: 0.37, 0.91). There was little evidence of reduced risk for those who breast-fed some children when the last born child was not breast-fed (OR: 0.91; 95% CI: 0.66, 1.26). Similar findings were noted in women with exactly two children and in those with two or more children. The protective influence of breast-feeding on ovarian cancer risk may be limited to women who breast-feed their last born child. These findings, which require confirmation by future studies, imply that breast-feeding resets pregnancy-related states that mediate ovarian cancer risk.

OBJECTIVE: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. METHODS: Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). RESULTS: We found no association with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71-1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06, p=0.38), and all other previously-reported associations. CONCLUSIONS: rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.

Purpose

Menstrual pain is associated with increased production of inflammatory molecules, such as prostaglandins. Inflammation is involved in pathogenesis of several cancers, including ovarian cancer. In this study we examined the association between menstrual pain and risk of ovarian cancer.

Methods

We conducted a case-control study with 2028 cases of epithelial ovarian cancer, and 2091 age and study center matched controls. Women were asked to report the severity of menstrual pain during their 20s and 30s, when not using oral contraceptives or breastfeeding. We used unconditional logistic regression to evaluate the association between menstrual pain and epithelial ovarian cancer risk overall, and polytomous logistic regression to evaluate whether the association differed across tumor subtypes.

Results

Risk of ovarian cancer was increased in women with moderate (OR=1.22, 95% CI: 1.05–1.42) and severe pain (OR = 1.34, 95% CI: 1.09–1.65) compared to women with no or mild pain during menstrual period. The association differed by histologic subtypes, with significant associations for severe pain with endometrioid (OR = 1.64, 95% CI: 1.15–2.34) and clear cell tumors (OR = 1.91, 95% CI: 1.11–3.28).

Conclusions

Our data suggest that moderate and severe pain during menstrual period is associated with increased risk of epithelial ovarian cancer. Due to high prevalence of menstrual pain in women of reproductive age this observation warrants further studies.

Recent epidemiologic evidence supports a role for MUC1 in ovarian carcinogenesis; therefore, we hypothesized that common genetic variation in the genes responsible for glycosylation of MUC1 may influence ovarian cancer risk. In a genome-wide association study of ovarian cancer, we observed an association between a non-synonymous SNP (rs2271077) in the UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosainyltransferase 2 (GALNT2) gene and ovarian cancer risk (p=0.005). We sought to validate the association in four population based ovarian cancer case-control studies collaborating through the Ovarian Cancer Association Consortium. Although rs2271077 was associated with a significantly increased risk (Odds Ratio (OR) = 1.37, 95% Confidence Interval (CI) = 1.06-1.77) in one study with 961 cases and 922 controls, we observed no association in the remaining three studies including 1452 cases and 1954 controls (OR=0.83, 95% CI= 0.66-1.04). Therefore, there appears to be no strong evidence of association between GALNT2 SNP rs2271077 and ovarian cancer risk.

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.