XPD Lys751Gln increases the risk of breast cancer.

Breast cancer incidence has been on the increase in south Indian women. Polymorphisms in DNA repair genes modify an individual's risk to cancer. XPD (Xeroderma pigmentosum D), a DNA helicase gene involved in nucleotide excision repair and transcription coupled repair, may affect an individual's DNA repair capacity, particularly that of bulky adducts. This case-control study (250 breast cancer cases and 500 healthy controls) aimed to investigate the role of the XPD Lys751Gln polymorphism as a risk factor in the development of breast cancer. Genotyping was performed using the Taq Man allelic discrimination assay. Immunohisto-chemistry was used to quantitate the level of polycyclic aromatic hydrocarbon (PAH) adducts in biopsy samples obtained from the breast cancer patients. Results showed that the XPD Gln/Gln genotype was significantly associated with an increased risk of breast cancer (OR, 1.75; 95% CI 1.02-2.80), particularly in premenopausal female patients (OR, 2.6; 95% CI 1.33-4.79). PAH adduct levels were significantly higher in the cases with breast cancer as compared to the normal breast tissue. This study reveals that XPD may play a role in increasing breast cancer risk particularly in premenopausal females.

CYP17 (T34C), CYP19 (Trp39Arg), and FGFR2 (C906T) polymorphisms and the risk of breast cancer in south Indian women.

Breast cancer is initiated by exposure to endogenous and exogenous estrogens. A case-control (n= 250-500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in CYP17 (T34C), CYP19 (Trp39Arg) and FGFR2(C906T). Genotyping was done using the Taqman allelic discrimination assay for CYP17 (T34C) and FGFR2 (T906C) and PCR-CTPP for CYP19 (Trp39Arg). There was a significant protective association of the (TT/CC) genotype of the CYP17 gene against the risk of developing breast cancer (OR= 0.68, 95% CI: 0.49-0.96), which was more significant in postmenopausal women (OR= 0.56, 95% CI: 0.35-0.89) (p= 0.015). CYP19 (Trp39Arg) is a rare polymorphism and all the cases were homozygous for the wild type Trp allele (100%); this was also the case for 99.2% of the controls. We were unable to detect any variant form of the CYP19 gene in south Indian women. There was no significant association between the risk of breast cancer and FGFR2 (C906T). These results suggest that the CYP17 TT/CC genotype is associated with decreased risk for breast cancer, especially in post menopausal women.

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.

Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and P53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer: a case control study from South India.

The present study was undertaken to examine the frequencies of GSTM1 (Null/Present), GSTP1 (Ile105Val) and p53 (Arg72Pro) genotypes and their relations to breast cancer susceptibility in South Indian women. This case - control study involved 250 consecutive breast cancer cases and 500 healthy controls matched in five-year age categories in the ratio of 1:2. Genotyping was performed by PCR for GSTM1, Real-Time Allelic discrimination assay for GSTP1 and PCR-CTPP for p53. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for the known risk factors for breast cancer. The frequencies for the GSTM1 Null genotype were 26% in the cases and 22% in the controls; for GSTP1 Ile/Ile, Ile/Val, Val/Val the frequencies were 46.6%, 41.9% and 11.5%, respectively, in cases and 46.0%, 43.8% and 10.2% in controls; for p53 Arg/Arg, Arg/Pro & Pro/Pro the frequencies were 26.4%, 50.0% and 23.6% in cases and 27.0%, 44.8% and 28.2% in controls. A nonsignificant elevation in breast cancer risk was observed among women who had the GSTM1 Null genotype (OR=1.24; 95% CI=0.83-1.84), the p53 Arg/Arg genotype (OR=1.28; 95% CI=0.81-2.03) and the Pro/Arg genotype (OR=1.49; 95% CI=0.99-2.25), and the GSTP1 Val/Val genotype (OR=1.1; 95% CI=0.64-1.91).