Role of p53 Codon72 SNP in breast cancer risk and anthracycline resistance.
OBJECTIVE
We undertook a case-control and a case-case study to examine the possible association of p53 codon72 polymorphism with the breast cancer risk and resistance to anthracycline-based chemotherapy.


METHODS
Case-control study: This study enrolled 175 patients with breast cancer treated at the Salah Aziez Institute and 159 healthy Tunisian women (matched for age, ethnicity and origin), used as a control, with no clinical evidence of any neoplastic disorder. Case-Case study: 400 breast cancer patients, with invasive ductal carcinoma (IDC) treated with anthracycline based-chemotherapy. Genomic DNA was isolated from whole-blood leucocytes using the phenol-chloroform method. Anthracycline response was scored according to the World Health Organization (WHO) criteria. P53 codon72 polymorphism was genotyped using real-time polymerase chain reaction (RT-PCR) with the TaqMan method. Data were statistically analyzed using the Chi-square test.


RESULTS
Clinical data revealed that among the 400 patients, one quarter was resistant to chemotherapy treatment. Genetic data revealed that the p53 Arg72Pro genotype was found to be greatly associated with breast cancer risk (p<0.001), as well as tumor site (p=0.046). However, resistance to anthracycline-based chemotherapy does not seem to be correlated with p53 codon72 polymorphism in our population. Also, the distribution of tumor size, lymph node involvement and tumor grade was not significantly different among the polymorphic variants.


CONCLUSIONS
We conclude that p53 codon72 polymorphism is involved in susceptibility to developing breast cancer. It may be a factor of progression when breast sites are taken into account. However, there is no evidence indicating that Arg72Pro SNP may influence response to anthracycline-based chemotherapy.
Salah Azaiz Institute, Tunis, Tunisia arfaouiabir@hotmail.com.
Abir
A
Arfaoui
Salah Azaiz Institute, Tunis, Tunisia.
Hayet
H
Douik
Salah Azaiz Institute, Tunis, Tunisia.
Ghalia
G
Kablouti
Salah Azaiz Institute, Tunis, Tunisia.
Arij Ben
AB
Chaaben
Salah Azaiz Institute, Tunis, Tunisia.
Nedia
N
Handiri
Salah Azaiz Institute, Tunis, Tunisia.
Zeineb
Z
Zid
Salah Azaiz Institute, Tunis, Tunisia.
Nessrine
N
Ouni
Salah Azaiz Institute, Tunis, Tunisia.
Farah
F
Zouiouch
Salah Azaiz Institute, Tunis, Tunisia.
Faiza
F
Ayari
Salah Azaiz Institute, Tunis, Tunisia.
Tesnim
T
Mamoughli
Salah Azaiz Institute, Tunis, Tunisia.
Jihen
J
Bouassida
Salah Azaiz Institute, Tunis, Tunisia.
Hajer
H
Abazza
Salah Azaiz Institute, Tunis, Tunisia.
Latif
L
Harzallaha
Salah Azaiz Institute, Tunis, Tunisia.
Fethi
F
Guemira
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon; D019008:Drug Resistance, Neoplasm; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D018943:Anthracyclines; D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
Breast cancer risk; anthracycline resistance; p53 codon72 polymorphism