Certain risk factors for ovarian cancer, such as nulliparity(ไม่เคยมีบุตร), may be more strongly associated with familial than with spontaneous ovarian cancer. Schildkraut et al. have reported that increased ovulatory cycles were associated with p53 overexpression in ovarian tumors, although others did not support this
Mutations of p53 are found more frequently in nonmucinous tumors, especially serous types, and may represent the accumulation of spontaneous DNA replication errors during normal epithelial cell proliferation associated with ovulation. Overexpression of p53 in borderline lesions, although uncommon, is associated with metastatic disease. Histologic differences in the patterns of p53 mutations may influence the association of ovarian cancer with ovulation-related risk factors such as parity, use of the oral contraceptive pill, and lactation. In addition to p53, the inactivation of the tumor suppressor gene PTEN is commonly found in endometrioid and clear cell tumors. In addition to tumor suppressor genes, oncogenes also have been shown to be overexpressed or mutated in association with ovarian cancer. For example, the overexpression of HER-2/neu in ovarian tissue is predictive of a poorer response to therapy and poorer survival in ovarian cancer patients.