Our findings suggest that rs3212986 polymorphism in 3'UTR of ERCC1 overlapped with CD3EAP may affect the repair of the damage induced by BPDE mainly via regulating ERCC1 expression and become a potential biomarker to predict smoking-related lung cancer.
A Chinese case-control analysis comprising 370 cases and 388 controls was conducted to evaluate the effects of the high-risk diplotype predefined as PPP1R13L rs1970764(AA)-CD3EAP rs967591(GG)-ERCC1rs11615(AA) among Caucasians and three SNPs alone or other haplotypes combined for lung cancer risk.
Using a panel of 20 lung cancer cell lines, including 15 NSCLC and 5 small cell lung cancers (SCLC), the mRNA expression levels for the RRM1, ERCC1 and ERCC2 genes were examined by quantitative real-time reverse transcription PCR.
Furthermore, a significant effect of SNPs in nucleotide excision repair pathway on lung cancer survival was observed among 185 stages III-IV patients treated with platinum-based chemotherapy without surgical operation: XPC rs2228000 (Ala499Val; P = 0.002) and ERCC1rs11615 (Asn118Asn; P = 0.012).
This meta-analysis suggests that the ERCC1 19007T>C polymorphism may be associated with lung cancer risk in Asians, while larger scale association studies are necessary to further validate the association of 19007T>C polymorphism with lung cancer risk.
In conclusion, this study indicated no association between mRNA expression of the DNA-repair genes ERCC1 and XPD and risk of subsequent development of lung cancer.
We compared the results of repeated staining of the entire original set of samples obtained from 589 patients in the International Adjuvant Lung Cancer Trial Biology study, which had led to the initial correlation between the absence of ERCC1 expression and platinum response, with our previous results in the same tumors.
MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P=0.004-0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk.
The ERCC1rs321986 GT and TT genotypes (at radon concentrations >200 Bq/m<sup>3</sup>) were more significantly associated with higher lung cancer risk (OR = 2.40, 95% CI = 1.29-4.45; OR = 4.45, 95% CI = 1.26-15.7, respectively).
We tested whether genetic variants in the ERCC1 gene are associated with susceptibility to lung cancer and efficacy of platinum-chemotherapy in patients with small cell lung cancer (SCLC).
Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity.
We have previously reported that both homozygote carriers of the A-allele as well as homozygous carriers of a high-risk haplotype (which includes the AA genotype in ERCC1G19007A) were at increased risk of basal cell carcinoma, breast cancer, and lung cancer among Caucasians.
Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02).
In this study, we examined the expression of excision repair cross-complementation group 1 (ERCC1) protein in 90 completely resected lung cancer samples from patients who received adjuvant or neo-adjuvant platinum-based chemotherapy.
We identified a sufficient number of epidemiologic studies on lung cancer to conduct a meta-analysis for genetic polymorphisms in nucleotide excision repair pathway genes, focusing on xeroderma pigmentosum group A (XPA), excision repair cross complementing group 1 (ERCC1), ERCC2/XPD, ERCC4/XPF and ERCC5/XPG.
In order to comprehensively capture common genetic variation in the ERCC1 gene, Caucasian data from the International HapMap project was used to assess linkage disequilibrium and choose four tagSNPs (rs1319052, rs3212955, rs3212948, and rs735482) in the ERCC1 gene to genotype 452 lung cancer cases, 175 H&N cancer cases, and 790 healthy controls.