Ovarian Cancer: Causes

Pathogenesis (disease development)

The pathogenesis of ovarian cancer is not yet fully understood. To date, ovarian cancer is thought to have a dual genesis:

  • Type 1 (“low grade”) carcinomas arise from defined precursor lesions such as borderline tumors
  • Type 2 (“high grade”; aggressive) carcinomas often arise from intraepithelial lesions (damage located within the epithelial layer) of the tubes (fallopian tubes).

Etiology (causes)

Biographical causes

  • Genetic burden from parents, grandparents (familial clustering of ovarian cancer (ovarian cancer) and breast cancer (breast cancer)); positive family history of ovarian cancer (= 9.8-fold increase in risk):
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: HOXD-AS1, SKAP1, TIPARP, XRCC2.
        • SNP: rs2072590 in the gene HOXD-AS1
          • Allele constellation: GT (1.2-fold).
          • Allele constellation: TT (1.4-fold)
        • SNP: rs9303542 in the gene SKAP1
          • Allele constellation: AG (1.1-fold).
          • Allele constellation: GG (1.2-fold)
        • SNP: rs2665390 in the gene TIPARP.
          • Allele constellation: CT (1.2-fold).
          • Allele constellation: CC (0.8-fold)
        • SNP: rs3814113 in an intergenic region.
          • Allele constellation: CT (0.8-fold).
          • Allele constellation: CC (0.8-fold)
        • SNP: rs3218536 in gene XRCC2
          • Allele constellation: AG (0.8-fold).
          • Allele constellation: AA (0.64-fold)
      • In women with a BRCA mutation, the risk – over a lifetime – of developing breast cancer is circa 60 to 80%. The lifetime risk of developing ovarian cancer (ovarian cancer) is circa 40 to 60 percent for BRCA1 mutation carriers and circa 10 to 30 percent for BRCA2 mutation carriers.
      • BRCA3 mutation (RAD51C) carriers also have a significantly increased risk of breast and ovarian cancer. However, the frequency (incidence) of RAD51C germline mutation carriers in high-risk families is estimated to be only about 1.5% to a maximum of 4% (BRCA1: about 15%, BRCA2: about 10%). The lifetime risk of breast cancer in RAD51C mutation carriers is reported to be approximately 60 to 80%, and the risk of ovarian cancer is reported to be approximately 20 to 40%.
  • Ethnic origin – belonging to the white race
  • Hormonal factors – childlessness
  • Occupations – occupational groups with occupational contact with carcinogens such as talc or asbestos.
  • Socioeconomic factors – high socioeconomic status.

Behavioral causes

  • Nutrition
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Overweight (BMI ≥ 25; obesity) (+ 10%).

Disease-related causes

  • Ascending (ascending) infections of the female reproductive organs.
    • Seropositivity (= individuals in whom antibodies to a specific antigen can be found) to Chlamydia/C. trachomatis occurred in 20% of ovarian cancer patients (12% of controls)
  • Endometriosis – benign disease in which endometrium grows in various locations inside and outside the uterus.
  • Mammary carcinoma (breast cancer)
  • Oligomenorrhea (cycles lasting more than 35 days) or frequent anovulation (cycles without ovulation): 2-fold increased risk of dying from ovarian cancer before age 70 (95 percent confidence interval 1.1 to 3.4); by age 77, 3-fold increased risk (95 percent confidence interval 1.5-6.7 for incidence and 1.4-5.9 for mortality)

Medications

  • Hormone therapy (HT) after menopause (the time of the last spontaneous menstrual period in a woman’s lifetime) – regardless of the type of HT (estrogen or an estrogen-progestin combination) – promotes the development of ovarian cancer. The Collaborative Group on Epidemiological Studies of Ovarian Cancer individually analyzed and pooled data from all relevant epidemiological studies:
    • Women who had received HT at any time had a 20% higher relative risk of cancer than women who never received HT.
    • Women who had just undergone HT were at highest risk. Their risk – studied prospectively – was 41% higher than that of never-HT users.
    • Women who had stopped HT but who had been on it for less than five years still had a 23% increased risk of ovarian cancer.
  • Estrogen or estrogen-progestin therapy may increase ovarian cancer risk; onset of effect with user durations of less than 5 years; risk reduces after discontinuation of therapy.
    • Menopausal hormone replacement therapy; risk increase of 43% after 5 years; decreases only slowly after discontinuation of therapy
  • Less frequent use of combined hormonal contraceptives (CHD; contraceptives) than the average woman

Environmental exposure – intoxications (poisonings).

  • Occupational contact with carcinogens such as asbestos or talc (talcum powder).
  • Hair dye