Risk factors associated with the development of a potential precursor to ovarian cancer.

B36 We have recently described a candidate preclinical marker for pelvic and ovarian serous cancer known as the “p53 signature” that is located in the distal fallopian tube and shares several attributes with carcinoma. To date, no epidemiological studies have been conducted to determine the risk factors associated with this microscopic entity. This study assessed the association of p53 signatures with several risk factors traditionally associated with ovarian cancer, including age, age at first childbirth, age at menopause, gravidity, parity, menarche, oral contraceptive use, body mass index (BMI), family history of breast cancer, and presence of cystic follicles. A cohort of 75 women from Brigham and Women9s Hospital (Boston, MA) with heritable BRCA mutations who underwent prophylactic salpingo-oophorectomy were studied. All tubes were immunostained for the presence of p53 signatures and signature positive and negative women were compared. Student’s T-tests and Chi-square tests were used on continuous and categorical variables respectively for the univariate analysis while logistic regression was used for multivariate analysis. These women ranged in age from 35 to 75 (mean 48) years. Twenty-nine (39%) scored positive for at least one p53 signature in the fallopian tube. Based on preliminary analysis, there was a statistically significant correlation between the p53 signature and age at first childbirth (p, t-test=0.03) and parity (p, t-test=0.01). Specifically, the odds ratio for women with first childbirth greater than or equal to 30 versus less than 30 was 3.8 (95% CI=1.2-12, p trend=0.15). The odds ratio for women with three childbirths or greater versus no childbirths was 0.18 (95% CI=0.04-0.87, p trend=0.05). After adjusting for age of first childbirth, parity and age, the trend test for age of first childbirth became nonsignificant (p=0.15), while the trend test for parity remained significant (p=0.05). We also observed non-statistically significant inverse association between p53 signature and BMI (p, t-test=0.13, p trend=0.13). Our preliminary results suggest that higher age at first childbirth and a lower parity, two factors associated with increased risk for ovarian cancer, segregate with the p53 signature. If our findings are confirmed, the p53 signature will merit consideration as a surrogate marker for ovarian cancer risk, and further study as an early step in serous carcinogenesis.