Risk factors for Ovarian cancer

1.

Elsevier ClinicalKey Clinical Overview

Diagnosis Subsubsection Title: Age: Occurs mostly in postmenopausal women, with peak incidence between ages 55 and 64 years, although it can occur in younger women, particularly those with hereditary cancer syndromes Subsubsection Title: Genetics: Hereditary breast and ovarian cancer syndrome (OMIM #604370, #612555, and others) Cancer predisposition condition caused by mutations in the BRCA1 and BRCA 2 genes (DNA repair–associated); various subtypes exist Increased risks for various cancers: early-onset breast, multiple breast primaries, male breast, epithelial ovarian, fallopian tube, and primary peritoneal Likelihood of identifying a BRCA 1 or BRCA 2 mutation in a woman with ovarian cancer at any age is around 13% to 18% Lynch syndrome #120435 #276300 Condition of constitutional mismatch repair deficiency caused by biallelic mutations in MSH2, MLH1, PMS2, or MSH6 Increased risk of ovarian cancer in addition to colorectal and other cancers, such as small intestine, hepatobiliary tract, urinary tract, brain, and skin Other inherited germline mutations associated with ovarian cancer include PALB2 , BARD1 , BRIP1, RAD51C , and RAD51D Subsubsection Title: Ethnicity/race: Incidence is higher in White women than in Black, Asian, or Hispanic women Subsubsection Title: Other risk factors/associations: The following factors appear to be associated with an increased risk of ovarian cancer: Family history of ovarian cancer in first-degree relative Polycystic ovary syndrome Endometriosis Obesity Hormone replacement therapy

Diagnosis The following factors appear to be associated with an increased risk of ovarian cancer: Family history of ovarian cancer in first-degree relative Polycystic ovary syndrome Endometriosis Obesity Hormone replacement therapy Transcutaneous hormone therapy may be associated with a lower risk of ovarian cancer than oral hormone therapy Unsuccessful infertility treatment (ovarian hyperstimulation) Intrauterine contraceptive use Cigarette smoking The following factors may be protective: Multiparity Oral contraceptive use Past breastfeeding Tubal ligation and hysterectomy

2.

Armstrong, Deborah K. (2024). In Goldman-Cecil Medicine (pp. 1375). DOI: 10.1016/B978-0-323-93038-3.00184-2

Approximately 20,000 new cases of ovarian cancer are diagnosed annually in the United States Unfortunately, most women have advanced disease at diagnosis, and 13,000 women die annually of their disease. As a result, ovarian cancer has the highest mortality rate of all gynecologic malignancies. Because the incidence of ovarian cancer is highest in developed countries where parity is lower, diets are higher in fat, and women have longer life expectancies, its incidence is highest in North America and Europe but lower in much of Asia and sub-Saharan Africa. The lifetime risk for ovarian cancer in women in the United States is 1:70, or 1 to 2%. The median age of onset for ovarian cancer is 60 to 65 years, although women with a genetic predisposition to ovarian cancer may develop the disease in their 40s or 50s. Although risk factors for ovarian cancer have been identified (Table 184-7), the cause of most ovarian cancers is not known. More frequent lifetime ovulation is associated with increased risk, and factors that suppress ovulation (e.g., pregnancy, use of oral contraceptives, and prolonged lactation) are associated with a decreased risk. Most of these risk factors are modest, with the exception of genetic predisposition related to inherited germline mutations in cancer-predisposing genes. The risk of ovarian cancer is lower in women who have had a tubal ligation, which may result in necrosis of the fallopian tube and death of tubal epithelial cells. A weak association with the use of powder in the genital area has been suggested by case-control studies but is controversial and not substantiated by cohort studies., Approximately 80% of ovarian cancers are sporadic, but about 15 to 20% can be linked to autosomal dominant germline mutations.BRCA1andBRCA2are the most common mutations, identified in about 15% of patients with advanced ovarian cancer (Chapter 166).

Inherited mutations in these genes are associated with a 5- to 30-fold increase in the lifetime risk of ovarian cancer and with a significantly increased risk for breast and other cancers (Table 184-8). In addition toBRCA1andBRCA2, other genes associated with an increased ovarian cancer risk includeATM,BRIP1, PALB2, BARD1, RAD51C, RAD51D, and the Lynch syndrome genes (MSH2, MLH1, PMS2, andMSH6).These genes combined are responsible for the remaining 5% of advanced ovarian cancers with an identified germline mutation. Most of these genes have a lower penetrance and may increase the lifetime risk of ovarian cancer to 5 to 15% or less.

3.

Elsevier ClinicalKey Derived Clinical Overview

• Individuals withMLH1, MSH2, MSH6, PMS2, EPCAMmutations. • By age 70, Lynch syndrome carriers have—in addition to an increased risk for colorectal, gastric, hepatobiliary, urinary tract, small bowel, brain, skin, and pancreatic cancers—up to an approximately twentyfold increase in ovarian cancer (4% to 12% risk vs. the general-population risk of 0.7%) and up to an approximately fortyfold increase in uterine cancer (25% to 60+% risk vs. the general-population risk of 1.6%). • The previously listed genes and others (e.g.,PTEN, TP53, CDH1, STK11) that are found less frequently are considered high-penetrance genes, as they can increase the relative risk of their respective syndromes by greater than four- to fivefold. • Other, more moderate-penetrant genes (e.g.,CHEK2, ATM, PALB2, BRIP1, RAD51C, RAD51D),that is, those that are associated with a two- to fourfold increase in the relative risk of cancer, should be considered when assessing risk and ordering genetic tests. • More than 12 known gene mutations are associated with an elevated risk for breast cancer, and a similar number are associated with an elevated risk for ovarian cancer. As such, screening forBRCA1, BRCA2alone will miss these mutations. • In addition to established deleterious mismatch repair gene mutations, gene alterations that are categorized in the literature as emerging risk mutations are also associated with hereditary gynecologic and other cancers.

4.

Ledermann JA, Raja FA, Fotopoulou C, et al. Annals of Oncology : Official Journal of the European Society for Medical Oncology. 2013;24 Suppl 6:vi24-32. doi:10.1093/annonc/mdt333.

Publish date: October 2, 2013.

]. There is variation in the incidence rate across the continent with a higher incidence in northern European countries. In the USA, there were ∼20 400 newly diagnosed cases and 14 400 deaths in 2009 [ ]. Ovarian cancer is the fifth most common type of cancer in women and the fourth most common cause of cancer death in women. The estimated lifetime risk for a woman developing ovarian cancer is about 1 in 54. Ovarian cancer is predominantly a disease of older, postmenopausal women with the majority (>80%) of cases being diagnosed in women over 50 years. The exact cause of ovarian cancer remains unknown but many associated risk factors have been identified. A woman's reproductive history appears to contribute significantly to her lifetime risk of ovarian cancer. Those women who have had multiple pregnancies have a lower risk than those with fewer pregnancies, who in turn have a lower risk than nulliparous women. Early menarche and late menopause also seem to contribute to a greater risk of ovarian cancer, while use of the oral contraceptive pill, tubal ligation, breastfeeding and suppression of ovulation offer protection against ovarian cancer. All of these risk factors point to ovulation being correlated with the development of ovarian cancer. Further risk factors are obesity and possibly the use of talcum powder. Family history plays a very important role in the development of ovarian cancer, although in a recent study 44% patients with high-grade serous ovarian cancer and a germline BRCA mutation did not report a family history of cancer [ ]. Women with a first-degree relative have more than a twofold increase in risk of ovarian cancer compared with women with no family history. However, only 10% of ovarian cancer cases have an identifiable genetic mutation, e.g. the known susceptibility genes BRCA 1 and BRCA 2. An inherited BRCA 1 mutation confers a 15%–45% lifetime risk of developing ovarian cancer and ≤85% risk of developing breast cancer. A BRCA 2 mutation increases the lifetime risk of ovarian cancer to 10%–20% and breast cancer risk of ≤85%. Women with hereditary ovarian cancer tend to develop the disease ∼10 years earlier than women with non-hereditary ovarian cancer. There are no clear guidelines for referral of ovarian cancer patients for testing.

5.

Food and Drug Administration (DailyMed).

Publish date: February 3, 2024.

Warnings And Cautions Ovarian Cancer The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95 percent CI, 0.77–3.24). The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years. 7 A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies. The relative risks associated with current use of hormonal therapy was 1.41 (95% confidence interval [CI] 1.32 to 1.50); there was no difference in the risk estimates by duration of the exposure (less than 5 years [median of 3 years] vs. greater than 5 years [median of 10 years] of use before the cancer diagnosis). The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27–1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown. 5.4 Probable Dementia In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg) -alone or placebo. After an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83–2.66).