Prospective evaluation of XRCC-1 Arg194Trp polymorphism as bio-predictor for clinical outcome in locally advanced laryngeal cancer undergoing cisplatin-based chemoradiation.

BACKGROUND: To determine X-ray repair cross-complementing 1 gene (XRCC-1) Arg194Trp polymorphism as bio-predictor for clinical outcome in advanced laryngeal squamous cell carcinoma undergoing cisplatin-based chemoradiation (CRT). METHODS: A total of 150 patients were enrolled in this prospective study. XRCC-1 Arg194Trp genotyping categorized patients as wild (C/C) and polymorphic (C/T or T/T). The primary endpoint was to assess acute radiation-induced toxicity (ARIT). RESULTS: A significant correlation of skin (P- .04) and oral mucosal ARIT (P- .01) was noticed in the XRCC-1 polymorphic variant. A higher treatment response was noted in the polymorphic variant, and it shows a trend toward significance (P- .08). With 33 months of median follow-up, 2-year progression-free survival (PFS) and overall survival (OS) of wild vs polymorphic variant were 34.6% vs 46.9% (P- .066) and 50.6% vs 62.2% (P- .12). CONCLUSION: XRCC-1 polymorphic variants have significantly higher grade of >2 ARIT and may have improved trend for treatment response and PFS.

Could excision repair cross-complementing group-1 mRNA expression from peripheral blood lymphocytes predict locoregional failure with cisplatin chemoradiation for locally advanced laryngeal cancer?

AIM: The association of excision repair cross-complementing 1 mRNA (ERCC-1 mRNA) expression with the outcome has been reported with immunohistochemistry (IHC) using tumor tissue in head and neck cancer. We evaluated ERCC-1 mRNA expression by reverse transcription polymerase chain reaction (RT-PCR) from peripheral blood lymphocytes (PBLs) as bio-predictor of locoregional failure (LRF) to chemoradiation (CRT) for locally advanced laryngeal squamous cell cancer (LALSCC). METHODS: A total of 107 male patients with LALSCC were enrolled in this prospective study. ERCC-1 mRNA expression by PBLs was determined by RT-PCR. Definitive CRT was delivered with 35 mg/m2 weekly cisplatin. Response Evaluation Criteria in Solid Tumor 1.1 (RECIST 1.1) were used in evaluating treatment response. The primary objective was to assess LRF. The influence of patient characteristics, treatment response, weekly cisplatin cycles, ERCC mRNA expression was determined for LRF, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 98 patients completed definitive CRT. The median value of 2-ΔΔCT ERCC-1 mRNA expression was 3.9; based on which it was categorized as low and high. Correlation of ERCC-1 expression with treatment response was insignificant (P- .38). With a median follow-up of 33 months; 2-year LRF, PFS, and OS was 63.3%, 34.7% and 79.4%. The 2-year LRF, PFS and OS for low versus high expression were 53.1% versus 73.5% (P-value = 0.036), 44.9% versus 24.4% (P-value = 0.047) and 81.6% versus 77.2% (P-value = 0.33), respectively. In multivariate analysis, ERCC-1 expression, T-stage, N-stage and tumor subsite are predictive factors for LRF; T-stage and nodal recurrence for OS; stage and treatment response for PFS. CONCLUSION: LALSCC patient with ERCC-1 mRNA low expression was associated with lower LRF rate, and improved PFS.

To investigate the affiliation of XRCC-1 Gene Arg194Trp polymorphism in alcohol and tobacco substance users and loco-regionally progressed Laryngeal squamous cell carcinoma.

OBJECTIVES: The correlation of XRCC-1 Gene Arg194Trp polymorphism with alcohol and tobacco substance user and with loco-regionally progressed squamous cell cancer of the larynx (LSCC) was assessed in this research study. The result of this research study is described herein. MATERIAL AND METHODS: A tertiary hospital-based observational case-control research was carried out. DNA segregation and Genotype examination were done from the blood sample of the control group and cases to know the correlation between XRCC-1 gene polymorphism with loco-regionally progressed LSCC and with hazard factors tobacco and alcohol. RESULTS: In the cases, the existence of DNA repair XRCC-1 gene polymorphic variants (Hetero CT and Mutant TT) was recognizable in contrary to the control group arm. The XRCC-1 gene polymorphic hetero (CT) genotype (O.R-1.96; 95% C.I: 1.23-3.13; P < 0.004) and mutant (TT) genotype variants (O.R-1.95; 95% C.I: 0.59-6.44; P = 0.27) was correlated with access hazard of loco-regionally progressed LSCC, and its statistically convincing for polymorphic hetero (CT) variant. The data were adapted for the age of the patients and control group, circadian alcohol intake, tobacco chewing habits, and the tobacco smoking habits during application of multivariate logistic regression. Its apparent that the hazard is amalgamated with hetero (CT) genotype variant (O.R- 1.67; 95% C.I: 0.98-2.82; P = 0.05) and mutant (TT) genotype variant (O.R- 1.62; 95% C.I: 0.88-2.78; P = 0.11) and its statistically convincing for polymorphic hetero (CT) genotype variant. Cases with the record of substance use (alcohol and tobacco) have an abundance of XRCC-1 hetero (CT) and mutant (TT) genotype variants in allegory to control group. Increased hazard is related with XRCC-1 hetero (CT) variant in smokers (O.R 3.28; 95% C.I: 1.45-7.41; P = 0.004), in tobacco chewers (O.R-3.79; 95% C.I: 1.87-7.71; P = 0.0002), and in alcohol consumers (O.R- 4.24; 95% C.I: 2.21-8.15; P= <0.0001) which is statistically significant. CONCLUSION: This research investigation demonstrates the correlation of XRCC-1 polymorphic hetero genotype (CT) & mutant genotype (TT) variants as hazard factor in loco-regionally progressed LSCC. Cases with the record of alcohol intake habits, tobacco smoking and chewing habits and XRCC-1 hetero genotype (CT) variant have statistically increased the hazard of loco-regionally progressed LSCC, which demonstrate the role of gene-ecological interconnection in modifying the vulnerability of loco-regionally progressed LSCC.