Single nucleotide polymorphisms of nucleotide excision repair pathway are significantly associated with outcomes of platinum-based chemotherapy in lung cancer

Abstract

Nucleotide excision repair (NER) pathway plays critical roles in repairing DNA disorders caused by platinum. To comprehensively understand the association between variants of NER and clinical outcomes of platinum-based chemotherapy, 173 SNPs in 27 genes were selected to evaluate association with toxicities and efficiency in 1004 patients with advanced non-small cell lung cancer. The results showed that consecutive significant signals were observed in XPA, RPA1, POLD1, POLD3. Further subgroup analysis showed that GTF2H4 presented consecutive significant signals in clinical benefit among adenocarcimoma. In squamous cell carcinoma, rs4150558, rs2290280, rs8067195 were significantly associated with anemia, rs3786136 was significantly related to thrombocytopenia, ERCC5 presented consecutive significant signals in response rate. In patients receiving TP regimen, significant association presented in neutropenia, thrombocytopenia and gastrointestinal toxicity. Association with anemia and neutropenia were found in GP regimen. rs4150558 showed significant association with anemia in NP regimen. In patients > 58, ERCC5 showed consecutive significant signals in gastrointestinal toxicity. Survival analysis showed SNPs in POLD2, XPA, ERCC6 and POLE were significantly associated with progression free survival, SNPs in GTF2H4, ERCC6, GTF2HA, MAT1, POLD1 were significantly associated with overall survival. This study suggests SNPs in NER pathway could be potential predictors for clinical outcomes of platinum-based chemotherapy among NSCLC.

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview

“…A number of aberrations identified as potential future therapeutic targets include several single nucleotide polymorphisms (SNPs) such as ERCC1, ERCC2, XRCC1, CCNH, GPX7, and ABCC4, which may play critical roles in neurotoxicity, as described in Table 1 and Fig. 1 [13][14][15][16][17][18][19]. One genomically targeted therapeutic intervention focuses on the protein, apurinic/apyrimidinic endonuclease (APE-1).…”

Prenatal diagnosis of cerebro‐oculo‐facio‐skeletal syndrome: Report of three fetuses and review of the literature

“…Here, we describe the phenotype of three fetuses with molecularly confirmed ERCC5/XPG COFS syndrome following termination of pregnancies for severe malformations. The detailed histological features provide new perspectives for the comprehension of XPG functions in developing tissues: abnormal cell proliferating compartments (thymus, liver—hematopoietic compartment, ganglionic eminences) at specific timepoints suggest that cell cycle deregulation could be major in the physiopathology of the disease, in line with the known association of ERCC5/XPG polymorphisms and cancer susceptibility (Shakil, Mubarik, Baig, Masood, & Chaudhry, ) or chemotherapy success (Song et al, ).…”

Genetic polymorphism ofSLC31A1is associated with clinical outcomes of platinum-based chemotherapy in non-small-cell lung cancer patients through modulating microRNA-mediated regulation

“…This study encompassed in total 1004 eligible patients (Chinese Han) histologically diagnosed with stage III-IV NSCLC between March 2005 and January 2010 from five hospitals in the East of China: Shanghai Chest Hospital, Shanghai Zhongshan Hospital, Shanghai Changhai Hospital, Shanghai Changzheng Hospital, and Cancer Hospital of Jiangsu Province. The recruitment criteria for enrolling eligible patients and their demographic characteristics such as gender, age at diagnosis, smoking status, ECOG performance status, clinical TNM stage, and tumor histological type were described in detail in our previous reports [ 36 – 39 ]. No statistically significant difference was observed in the distribution of demographic features among the patients from the six hospitals ( P gender = 0.698, P age = 0.321).…”