Influence of (C1236T and C3435T) Polymorphisms of ABCB1 Gene on Chemotherapy Treatment Outcome and Toxicity in Breast Cancer Patients.

BACKGROUND: ATP Binding Cassette Transporters (ABCB1) gene plays an important role in transport of different metabolites and anticancer drugs across the cell membrane. There is lack of knowledge on ABCB1 gene polymorphism and its correlation with Adriamycin or paclitaxel based chemotherapy induced toxicity in breast cancer patients. Therefore in this study, we explored the correlation of ABCB1 polymorphisms gene on response and toxicity in adriamycin and paclitaxel based chemotherapy in breast cancer patients from Indian population. METHODS: Two hundred BC patients receiving Adriamycin and paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in ABCB1 gene (C1236T, C3435T) were studied by PCR and RFLP analysis. RESULTS: The univariate logistic regression analysis showed statistically significant negative association with protective effects of ABCB1 (C3435T) polymorphism with heterozygous genotype (OR=0.34, 95% CI: 0.13-0.89; p=0.027), homozygous variant genotype (OR=0.31, 95% CI: 0.10-0.99; p=0.049) and combined C/T+T/T genotypes (OR=0.33, 95% CI: 0.13-0.79; p=0.013) in relation with severe toxicity of chemotherapy induced nausea and vomiting in breast cancer patients treated with Adriamycin chemotherapy. The 3435 C>T polymorphism of ABCB1 gene with heterozygous C/T genotype showed significantly negative association (OR=0.37, 95% CI: 0.14-0.96; p=0.042) with peripheral neuropathy in patients treated primarily with paclitaxel thereafter Adriamycin. CONCLUSION: The findings obtained from this study revealed significant association of ABCB1 3435 C>T polymorphisms with non-hematological toxicity in response to adriamycin and paclitaxel based chemotherapy.

Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra.

BACKGROUND: The present study was planned to investigate possible association of single nucleotide polymorphisms (SNPs) of nucleotide excision repair (NER) genes such as XPC, XPD, XPG with acute radiation induced toxicities such as skin reactions and oral mucositis in normal tissue from head and neck cancer (HNC) patients receiving radiotherapy.  Methods: Two hundred and fifty HNC patients receiving radiotherapy were enrolled in this study and the acute toxicity reactions and radiation response were recorded. Association of SNPs rs2228001 of XPC, rs238406, rs13181 of XPD and rs17655 of XPG gene with normal tissue reactions in the form of dermatitis and mucositis were studied by PCR-RFLP and direct DNA sequencing. RESULTS: The results of univariate analysis of SNPs of XPC, XPD and XPG showed that XPC polymorphism at codon 939 of exon 15 (A>C) was not associated with dermatitis (OR=0.30, 95% CI: 0.06-1.39; p=0.125), or oral mucositis (OR=1.14, 95% CI: 0.41-3.20; p=0.793). The XPD codon 156 of exon 6 (C>A) and codon 751 of exon-23 A>C) polymorphism showed no association with radiosensitivity in HNC patients (OR=1.50, 95% CI: 0.60-3.71; p=0.080) for dermatitis, (OR=1.54, 95% CI: 0.66-3.61; p=0.312) for oral mucositis. The 1104 Asp variant genotype or allele of XPG (OR=1.35 95% CI: 0.50-3.64; p=0.541) showed no association with degree of radiotherapy associated dermatitis or mucositis (OR=0.80, 95% CI: 0.32-2.03; p=0.648) in HNC patients. The variant C allele of 2920 A/C genotype of XPC gene at codon 939 of exon 15, found protective with developing skin reactions with grade >1 (OR=0.60, 95% CI: 0.36-0.97; p=0.039) in HNC patients treated with radiotherapy. CONCLUSION: The results obtained in this study concluded that the SNPs rs2228001of XPC, rs238406, rs13181 SNPs of XPD and rs17655 SNP of XPG are not associated with normal tissue toxicity in HNC patients treated with radiotherapy. Radiotherapy with high radiation dose was significantly associated with oral mucositis in response to radiotherapy.

Single Nucleotide Polymorphisms in DNA Repair Genes (XRCC1, XRCC2, XRCC3) and Their Association with Radiotherapy Toxicity among Head and Neck Cancer Patients:A Study from South-Western Maharashtra.

BACKGROUND: The genetic polymorphisms in DNA repair genes and their correlation with normal tissue toxicity in response to radiation therapy has not been consistently proven in many of the studies done in head and neck cancers (HNC). This study was intended to investigate the association of most common single nucleotide polymorphisms of DNA repair genes with acute radiation induced toxicities such as skin reactions and oral mucositis in normal tissue from HNC patients receiving radiotherapy from South-Western Maharashtra. METHODS: Two hundred HNC patients receiving radiotherapy were enrolled in this study and the radiation injuries in the form of skin reactions and oral mucositis were recorded. Three single nucleotide polymorphisms (SNPs) rs1799782, rs25489) rs25487 of XRCC1 gene, rs3218536in XRCC2 gene and rs861539 SNP of XRCC3 gene were studied by PCR-RFLP and direct DNA sequencing.  Results: The univariate analysis of SNPs of XRCC1, XRCC2 and XRCC3, the obtained results verified that XRCC1 polymorphism at 194Trp of exon 6 (OR=0.69, 95% CI: 0.28-1.71; p=0.433), codon 280 at exon 9 ((OR=1.05, 95% CI: 0.42-2.63; p=0.911) and codon 399 of at exon 10(OR=1.06, 95% CI: 0.52-2.15; p=0.867) and XRCC2 polymorphism at codon 188 at exon 3 (OR=1.07, 95% CI: 0.46-2.47; p=0.866) and 241Met variant genotype of XRCC3 (OR=2.63 95% CI: 0.42-16.30; p=0.298) showed no association with degree of radiotherapy associated dermatitis or mucositis in HNC patients. CONCLUSION: The findings from this study postulated that none of rs1799782, rs25489, rs25487 SNPs of XRCC1, rs3218536 SNP of XRCC2 nor rs861539 SNP of XRCC3 were associated with increased toxicity of radiotherapy in HNC patients of south-western Maharashtra. 
.