The Role of Statins in the Prevention of Ovarian and Endometrial Cancers.

Ovarian and endometrial cancers are the most common gynecologic malignancies and emerging evidence suggests that lipid metabolism and subsequent inflammation are important etiologic factors for both tumors. Statins (HMG-CoA reductase inhibitors) are the most widely prescribed lipid-lowering drugs in the United States and are used by 25% of adults aged 40+ years. In addition to their cardio-protective actions, statins have anti-inflammatory effects and have demonstrated antiproliferative and apoptotic properties in cancer cell lines, supporting a potential role in cancer prevention. To appropriately quantify potential public health impact of statin use for cancer prevention, there is a great need to understand the potential risk reduction among individuals at a higher risk of gynecologic cancers, the group that will likely need to be targeted to effectively balance risk/benefit of medications repurposed for cancer prevention. In this commentary, we focus on summarizing emerging evidence suggesting that the anti-inflammatory and lipid-lowering mechanisms of statins may provide important cancer-preventive benefits for gynecologic cancers as well as outline important unanswered questions and future research directions.

Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis.

BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies.

Association of Anti-Mullerian Hormone, Follicle-Stimulating Hormone, and Inhibin B with Risk of Ovarian Cancer in the Janus Serum Bank.

BACKGROUND: Reproductive factors, including parity, breastfeeding, and contraceptive use, affect lifetime ovulatory cycles and cumulative exposure to gonadotropins and are associated with ovarian cancer. To understand the role of ovulation-regulating hormones in the etiology of ovarian cancer, we prospectively analyzed the association of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B with ovarian cancer risk. METHODS: Our study included 370 women from the Janus Serum Bank, including 54 type I and 82 type II invasive epithelial ovarian cancers, 49 borderline tumors, and 185 age-matched controls. We used conditional logistic regression to assess the relationship between hormones and risk of ovarian cancer overall and by subtype (types I and II). RESULTS: Inhibin B was associated with increased risk of ovarian cancer overall [OR, 1.97; 95% confidence interval (CI), 1.14-3.39; P trend = 0.05] and with type I ovarian (OR, 3.10; 95% CI, 1.04-9.23; P trend = 0.06). FSH was not associated with ovarian cancer risk overall, but higher FSH was associated with type II ovarian cancers (OR, 2.78; 95% CI, 1.05-7.38). AMH was not associated with ovarian cancer risk. CONCLUSIONS: FSH and inhibin B may be associated with increased risk in different ovarian cancer subtypes, suggesting that gonadotropin exposure may influence risk of ovarian cancer differently across subtypes. IMPACT: Associations between prospectively collected AMH, FSH, and inhibin B levels with risk of ovarian cancer provide novel insight on the influence of premenopausal markers of ovarian reserve and gonadotropin signaling. Heterogeneity of inhibin B and FSH effects in different tumor types may be informative of tumor etiology.

Historical cancer incidence and mortality assessment in an Illinois community proximal to a former manufactured gas plant.

OBJECTIVES: Concern has been raised that the occurrence of cancer may be increased in neighbourhoods around a former manufactured gas plant in Champaign, Illinois, USA. Thus, we compared historical rates of cancer in this area to comparison communities as well as with nationally standardised rates. DESIGN: Retrospective population-based community cancer assessment during 1990-2010. SETTING: Champaign County, Illinois, USA, and zip codes encompassing the location of the former manufactured gas plant to counties that were similar demographically. PARTICIPANTS: Residents of the counties and zip codes studied between 1990 and 2010. MAIN OUTCOME MEASURES: The relative risk (RR) and 95% CI were used to compare cancer incidence and mortality in the areas near the gas compression site to the comparison counties. Standardised incidence ratios (SIRs) were calculated to compare rates in the areas near the gas compression site to expected rates based on overall US cancer rates. RESULTS: Total cancer mortality (RR=0.91, 95% CI 0.88 to 0.94) and incidence (RR=0.95, 95% CI 0.94 to 0.97) were reduced significantly in Champaign County versus the comparison counties. Similarly, a reduced rate of total cancer was observed in analyses by zip code (proximal to the former gas plant) when compared with either similar counties (RR=0.89, 95% CI 0.86 to 0.93) or national standardised rates of cancer (SIR=0.88, 95% CI 0.85 to 0.91). CONCLUSIONS: This historical cancer assessment did not find an increased risk of total cancer or specific cancer types in communities near a former manufactured gas plant site.