What are the at-risk groups for ovarian cancer, particularly in terms of family history, genetic mutations, age, reproductive history, and other medical conditions?

At-Risk Groups for Ovarian Cancer

Genetic Mutations (Highest Risk)

Women with BRCA1 or BRCA2 mutations face dramatically elevated ovarian cancer risk and represent the most critical at-risk group requiring intensive management. 1

• BRCA1 mutation carriers have a cumulative lifetime risk of 48.3% (38.8%-57.9%) for ovarian cancer by age 70 1, with other estimates ranging from 37-62% 1 to 56% 2
• BRCA2 mutation carriers have a cumulative lifetime risk of 20.0% (13.3%-29.0%) by age 70 1, with estimates ranging from 11-23% 1
• BRCA mutations account for approximately 90% of hereditary ovarian cancer cases, which comprise 5-10% of all ovarian cancers overall 1, 3
• In population-based studies of unselected ovarian cancer patients, 3.8-14.5% carry BRCA1 mutations and 4.2-5.7% carry BRCA2 mutations 1
• Lynch syndrome (hereditary nonpolyposis colorectal cancer) confers a cumulative ovarian cancer risk exceeding 12%, with diagnosis typically at younger ages 1, 3

Family History (Second Highest Risk)

Family history represents the strongest clinical risk factor for ovarian cancer, even in the absence of identified genetic mutations. 3

• Women with two or more first- or second-degree relatives with ovarian cancer have significantly elevated risk and should be referred for genetic counseling 1, 4
• Women with a combination of breast and ovarian cancer in first- or second-degree relatives on the same side of the family require genetic counseling 1, 4
• Single first-degree relative with ovarian cancer confers more than a twofold increase in ovarian cancer risk 1
• In families with two or more confirmed ovarian cancers, the relative risk is 7.18 (3.82-12.3), with absolute risk by age 70 of 11% 5
• Even in families testing negative for BRCA1/2 mutations, ovarian cancer risk remains elevated at 11.59 (3.12-29.7), suggesting other susceptibility genes 5

Ashkenazi Jewish Ancestry

Women of Ashkenazi Jewish descent have specific, lower-threshold criteria for genetic counseling referral. 1, 4

• Referral indicated with one first-degree relative OR two second-degree relatives on the same side with breast or ovarian cancer 1, 4
• This population has higher prevalence of specific BRCA founder mutations 1

Age-Related Risk

Ovarian cancer is predominantly a disease of postmenopausal women, with risk increasing substantially after age 50. 1

• Over 80% of cases are diagnosed in women over age 50 1
• Estimated lifetime risk for women in the general population is approximately 1 in 54 1
• Hereditary ovarian cancers typically develop approximately 10 years earlier than sporadic cases 1

Reproductive History Factors

Reproductive factors related to ovulation frequency significantly influence ovarian cancer risk. 1

Increased Risk:

• Nulliparity (never having been pregnant) 1
• Early menarche and late menopause (prolonged ovulatory years) 1
• Fewer pregnancies 1

Protective Factors:

• Multiple pregnancies provide substantial protection 1
• Oral contraceptive use reduces risk by approximately 50% 2, 4
• Breastfeeding 2, 4
• Bilateral tubal ligation 2, 4
• Suppression of ovulation 1

Other Medical and Lifestyle Factors

• Obesity increases ovarian cancer risk 1
• Possible association with talcum powder use 1

Critical Clinical Pitfall

44% of patients with high-grade serous ovarian cancer and germline BRCA mutations report NO family history of cancer, emphasizing that absence of family history does not exclude genetic risk. 1 This underscores the importance of considering genetic testing based on tumor characteristics (such as triple-negative breast cancer or high-grade serous ovarian cancer) even without apparent family history.