Risk Factors for Candidate Precursors of Serous Cancer in Tubal Epithelium of BRCA Mutation Carriers
PA Shaw, D Vicus, A Finch, P Sun, S Armel, SA Narod. University Health Network, Toronto, ON, Canada; Women's College Hospital, Toronto, ON, Canada
Background: Candidate precursors of high grade serous carcinoma in tubal epithelium have been reported, and include the p53 signature and the Tubal Intraepithelial Carcinoma (TIC). Both lesions have been identified in prophylactic salpingectomy specimens from BRCA1/2 mutation carriers. In support of the theory that these lesions may play a role in the development of serous cancer, we sought to identify risk factors for these non-invasive tubal lesions, and to compare these risk factors with the traditional risk factors for ovarian cancer.
Design: We have previously reported the incidence of pre-invasive lesions in prophylactic salpingectomy specimens from 173 BRCA mutation carriers. Each participant from that study was asked to complete a risk-factor questionnaire, which included information on their reproductive and medical history and various lifestyle factors. Women for whom a tubal lesion was found (cases) were compared to women with no lesion (controls). Student's t test was used to test for statistical significance for continuous variables and the Fisher exact was used for categorical variables.
Results: Of the 173 patients, 43 (25%) were found to have a tubal abnormality, including 23% of the BRCA1 mutation carriers and 27% of the BRCA2 mutation carriers. The prevalence of a non-invasive tubal lesion increased with age; an abnormality was present in 5% of women who had surgery before the age of 40 (1 of 12) and in 56% of women who underwent surgery at age 60 or above (6 of 13; p = 0.004). The prevalence of either non-invasive lesion was lower for women who had used an oral contraceptive for ten or more years (2.9%), compared to women who had one to nine years of use (29.2%). A non-invasive lesion of either type was found in 31.2% of women with a BMI > 25 kg/m2 ) compared to 18.0% of patients with a BMI <25 kg/m2 at the time of surgery (p = 0.05). Additional variables evaluated included parity, age at first birth, breastfeeding, hormone replacement therapy use, previous breast cancer. None of these variables was associated with the presence of p53 signature or TIC.
Conclusions: We have demonstrated that some but not all known ovarian cancer risk factors are also risk factors for putative cancer precursors in tubal epithelium. The prevalence of p53 signature and TIC increases with age at salpingectomy and with BMI. Long-term oral contraceptive use is associated with a decrease in the prevalence of both lesions.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 145, Tuesday Afternoon