TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy.
The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.
Rajkumar
Thangarajan
T
Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai, 600020, India. rajkumart@yahoo.com
Samson
Mani
M
Rama
Ranganathan
R
Sridevi
Veluswami
V
Mahji
Urmila
U
Swaminathan
Rajaraman
R
Nancy
Nirmala K
NK
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy*; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D004273:DNA, Neoplasm / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007194:India / Q000453:epidemiology; D008408:Mastectomy; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000099222:betaIG-H3 Protein
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D016326:Extracellular Matrix Proteins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D000099222:betaIG-H3 Protein; C495901:TP53 protein, human; C496556:GSTP1 protein, human