Open AccessMutations in p53 , p53 protein overexpression and breast cancer survival
Author(s) -
Rossner Jr Pavel,
Gammon Marilie D.,
Zhang YuJing,
Terry Mary Beth,
Hibshoosh Hanina,
Memeo Lorenzo,
Mansukhani Mahesh,
Long ChangMin,
Garbowski Gail,
Agrawal Meenakshi,
Kalra Tara S.,
Gaudet Mia M.,
Teitelbaum Susan L.,
Neugut Alfred I.,
Santella Regina M.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00553.x
Subject(s) - missense mutation , breast cancer , hazard ratio , cancer research , biology , medicine , mutation , oncology , nonsense mutation , population , exon , odds ratio , cancer , confidence interval , gene , genetics , environmental health
p53 is an important tumour suppressor gene that encodes p53 protein, a molecule involved in cell cycle regulation and has been inconsistently linked to breast cancer survival. Using archived tumour tissue from a population‐based sample of 859 women diagnosed with breast cancer between 1996 and 1997, we determined p53 mutations in exons 5–8 and p53 protein overexpression. We examined the association of p53 mutations with overexpression and selected tumour clinical parameters. We assessed whether either p53 marker was associated with survival through 2002, adjusting for other tumour markers and prognostic factors. The prevalence of protein overexpression in the tumour was 36% (307/859) and of any p53 mutation was 15% (128/859). p53 overexpression was positively associated with the presence of any p53 mutation (odds ratio [OR]= 2.2, 95% confidence interval [CI]= 1.5–3.2), particularly missense mutations (ER = 7.0, 95% CI = 3.6–13.7). Negative oestrogen and progesterone receptor (ER/PR) status was positively associated with both p53 protein overexpression (= 2.6, 95% CI = 1.7–4.0) and p53 mutation (OR = 3.9, 95% CI = 2.4–6.5). Any p53 mutation and missense mutations, but not p53 protein overexpression, were associated with breast cancer‐specific mortality (hazard ratio [HR]= 1.7, 95% CI = 1.0–2.8; HR = 2.0, 95% CI = 1.1–3.6, respectively) and all‐cause mortality (HR = 1.5, 95% CI = 1.0–2.4; HR = 2.0, 95% CI = 1.2–3.4, respectively); nonsense mutations were associated only with breast cancer‐specific mortality (HR = 3.0, 95% CI = 1.1–8.1). These associations however did not remain after adjusting for ER/PR status. Thus, in this population‐based cohort of women with breast cancer, although p53 protein overexpression and p53 mutations were associated with each other, neither independently impacted breast cancer‐specific or all‐causing mortality, after considering ER/PR status.