Dietary fat intake and risk of epithelial ovarian cancer by tumour histology.

BACKGROUND: Studies of fat intake and epithelial ovarian cancer (EOC) risk have reported inconsistent findings, hence we hypothesised that associations may vary by histologic subtype. METHODS: We evaluated fat intake in a New England case-control study including 1872 cases and 1978 population-based controls (1992-2008). Epithelial ovarian cancer risk factors and diet were assessed using a food frequency questionnaire at enrolment. Logistic regression was used to estimate associations between fat intake and EOC risk and polytomous logistic regression was used to test whether associations varied by histologic subtype. RESULTS: We observed a decreased risk of EOC when comparing the highest vs lowest quartiles of intake of omega-3 (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.66-0.96, P-trend=0.01) and omega-6 (OR=0.77, 95% CI 0.64-0.94, P-trend=0.02) and an increased risk with high consumption of trans fat (OR=1.30, 95% CI 1.08-1.57, P-trend=0.002). There was no significant heterogeneity by tumour histologic subtype; however, we observed a strong decreased risk for endometrioid invasive tumours with high intake of omega-3 (quartile (Q) 4 vs Q1, OR=0.58, 95% CI 0.41-0.82, P-trend=0.003). CONCLUSIONS: These findings suggest that higher intake of omega-3 may be protective for EOC overall and endometrioid tumours in particular, whereas greater consumption of trans fat may increase risk of EOC overall.

Reproductive characteristics in relation to ovarian cancer risk by histologic pathways.

STUDY QUESTION: Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification? SUMMARY ANSWER: Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer. WHAT IS KNOWN ALREADY: Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways. DESIGN: This case-control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center. MAIN RESULTS AND THE ROLE OF CHANCE: We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36-2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥ 3 versus 0 children, OR = 0.15, 95% CI: 0.11-0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥ 3 versus 0 children, OR = 0.13, 95% CI: 0.10-0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78-3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility. LIMITATIONS, REASONS FOR CAUTION: A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study. WIDER IMPLICATIONS OF THE FINDINGS: This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types. STUDY FUNDING/COMPETING INTEREST(S): This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Serum prolactin and TSH in an in vitro fertilization population: is there a link between fertilization and thyroid function?

PURPOSE: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. METHODS: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. RESULTS: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. CONCLUSION: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.