Risk Factors for Ovarian Cancer: An Umbrella Review of the Literature

Abstract

Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11–1.20), body mass index (BMI) (RR ≥ 30 kg/m2 versus normal 1.27, 95% CI 1.17–1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69–0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.

Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision

“…Other modifiable risk factors include the use of hormonal-based contraception, breastfeeding, pregnancy, avoidance of tamoxifen and prevention of diabetes 394–396 . Modifiable risk factors for ovarian cancer in the general population include obesity, hormone replacement therapy and nulliparity 397 . As with endometrial cancer, the use of hormonal contraception is thought to be protective against ovarian cancer 397 .…”

“…Modifiable risk factors for ovarian cancer in the general population include obesity, hormone replacement therapy and nulliparity 397 . As with endometrial cancer, the use of hormonal contraception is thought to be protective against ovarian cancer 397 . For cervical cancer, factors that reduce an individual’s exposure to HPV or increase their ability to clear HPV are seen as protective.…”

Immune pathway through endometriosis to ovarian cancer

“…Although endometriosis is a benign disease, more and more studies support that it has been linked with an increased chance of developing ovarian cancer, representing an earlier stage of neoplastic processes[ 9 - 11 ]. The first histological correlation between endometriosis tissue and ovarian cancer specimens was first presented by Sampson (1925), proposing that endometrial ovarian cancer may develop from endometriotic tissue, creating some criteria for diagnosis: (1) Evidence of coexisting tumor and endometriosis in the same ovarian location; (2) exclusion of a second malignancy elsewhere; and (3) histological pattern that resembles endometrial origin[ 12 ].…”

Metastatic Ovarian Cancer: Bibliographic Analysis

“…Typical for the metastatic process of ovarian cancer is intra-abdominal spread, which is manifested by peritoneal carcinomatosis [3,4]. The most common sites of distant metastases of ovarian cancer are the pleura, lungs, heart, and lymph nodes [5,6].…”