Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses

Abstract

Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value<0.001), BSML rs1544410 (OR=1.078; 95 %CI (1.024, 1.153); P-value=0.004), and Fokl rs2228570 (OR=1.123; 95 % CI (1.089, 1.157); P-value<0.001), which were significantly associated with increasing risk of ovarian cancer. Among the other factors, coffee intake (OR=1.106; 95 % CI (1.009, 1.211); P-value=0.030), hormone therapy (RR=1.057; 95 % CI (1.030, 1.400); P-value<0.001), hysterectomy (OR=0.863; 95 % CI (0.745, 0.999); P-value=0.049), and breast feeding (OR=0.719, 95 % CI (0.679, 0.762) and P-value<0.001) were mostly reported in studies. Among nutritional factors, coffee, egg, and fat intake significantly increase the risk of ovarian cancer. Estrogen, estrogen-progesterone, and overall hormone therapies also are related to the higher incidence of ovarian cancer. Some diseases, such as diabetes, endometriosis, and polycystic ovarian syndrome, as well as several genetic polymorphisms, cause a significant increase in ovarian cancer occurrence. Moreover, other factors, for instance, obesity, overweight, smoking, and perineal talc use, significantly increase the risk of ovarian cancer.

Etiopathogenesis of ovarian cancer. An inflamm-aging entity?

“…OvCa is a multifactorial disease, including demographic, reproductive, gynecologic, hormonal, genetic, and lifestyle factors ( Tanha et al, 2021 ).…”

“…Among other factors, such as hereditary, environmental, and lifestyle factors, inflammation is an important risk factor for OvCa. Several studies have suggested that factors related to ovarian surface epithelium (OSE) inflammation, such as ovulation, endometriosis, and pelvic inflammatory diseases (PIDs), are associated with an increased risk of OvCa ( Trabert et al, 2020 , Tanha et al, 2021 ). Mucin 16 (MUC16) is a membrane-associated gene that encodes cancer antigen 125 (CA125), and the upregulation of its expression is another mechanism underlying the effects of inflammatory factors in OvCa ( Liu et al, 2021 ).…”

An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study

“…Obesity may increase the risk of EC by a variety of mechanisms, including the conversion of androgens to estrogens via the aromatase activity [ 10 ]. OC is also associated with hormonal factors, such as nulliparity, early-onset menarche, late-onset menopause, and the use of hormonal treatments [ 4 , 11 ]. Other factors that interact with sex hormones could potentially modify the risk of EC and OC.…”

The Emerging Role of Cyclin-Dependent Kinase Inhibitors in Treating Diet-Induced Obesity: New Opportunities for Breast and Ovarian Cancers?

“…Obesity is also a well-established risk factor for breast cancer (BC) [ 11 ] and ovarian cancer (OC) [ 12 ], which are among the most commonly diagnosed tumors in women worldwide, and a leading cause of cancer mortality [ 13 , 14 , 15 , 16 ]. Although epidemiologic data have associated obesity with increased risk of cancer development and progression for a variety of tumors long ago, only recently the underlying molecular mechanisms have begun to be characterized [ 17 , 18 ].…”