Risk factors for a serous cancer precursor ("p53 signature") in women with inherited BRCA mutations.
OBJECTIVE
Pelvic (ovarian) serous carcinomas frequently contain p53 mutations. Recently, a candidate serous cancer precursor (the p53 signature) with p53 mutations and other features in common with serous cancer has been discovered in distal fallopian tube mucosa. This study examined the relationship of putative ovarian cancer risk factors with the presence of p53 signatures in women with BRCA mutations (BRCA+).


METHODS
Fallopian tubes from 75 BRCA+ women were immunostained for p53 signatures and correlated with age at first childbirth, parity, oral contraceptive use, body mass index (BMI), and BRCA subtype (1 or 2). Statistical analysis was performed with the T-test or Chi-square analysis and logistic regression adjusting for age and parity.


RESULTS
Thirty-eight percent of the tubes contained p53 signatures, which were significantly associated with older age at first childbirth (mean 30.8 vs. 28.4 years; p=0.04) and lower parity (mean 1.4 vs. 2.2; p=0.01) in univariate analyses. The unadjusted odds ratios were 3.8 (p-trend=0.04) for first childbirth>/=30 years versus <30 and 0.2 (p-trend=0.01) for parity >/= 3 versus nulliparous women. After adjusting for age and parity, the trend for age at first childbirth became non-significant (adjusted odds ratio 3.5; p-trend=0.15), while that for parity remained significant (adjusted odds ratio 0.2; p-trend 0.02).


CONCLUSIONS
The p53 signature is significantly associated with lower parity and possibly higher age at first childbirth, further linking this entity to serous cancer via risk factors associated with ovulation. The p53 signature merits consideration as a surrogate marker for serous cancer risk.
Saleemuddin
Aasia
A
Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Folkins
Ann K
AK
Garrett
Leslie
L
Garber
Judy
J
Muto
Michael G
MG
Crum
Christopher P
CP
Tworoger
Shelley
S
D000328:Adult; D000368:Aged; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010052:Ovariectomy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53