DNA Repair Gene Polymorphisms in Non-Small-Cell Lung Cancer Patients Treated with First-Line Platinum-Containing Chemotherapy

Rulli, Eliana; Marabese, Mirko; Piva, Sheila; Bonomi, Lucia; Caiola, Elisa; Ganzinelli, Monica

doi:10.5301/tj.5000526

Cited by 4 publications

(5 citation statements)

References 41 publications

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“…In accordance with what was found in other studies [22,34], the current study showed no statistically significant difference between the different genotypes in both SNPs and neither PFS nor OS. On the contrary, these findings contradict what was found in a trial on NSCLC patients where the TT genotype of rs1047768 had statistically significant shorter PFS and OS compared to the CC genotype [39].…”

Section: Discussionsupporting

confidence: 93%

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Variants of ERCC5 and the outcome of platinum-based regimens in non-small cell lung cancer: a prospective cohort study

et al. 2022

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Excision repair complementary complex 5 (ERCC5) is an important component in the repair pathway of platinum-induced damage. The current study evaluated the effect of ERCC5 variants (rs751402 and rs1047768) on the clinical outcome of platinum-based regimens in non-small cell lung cancer (NSCLC) patients. A prospective, cohort study was conducted on 57 newly diagnosed NSCLC Egyptian patients. Patients received either cisplatin or carboplatin-based chemotherapy. DNA was extracted and the variants were analyzed using real time PCR. This study found no significant difference between the studied variants and patients’ response to chemotherapy, progression-free survival (PFS) or overall survival (OS). However, a statistically significant association was found between the histologic subtypes and the studied variants (p = 0.028 and 0.018 for rs751402 and rs1047768, respectively). A statistically significant association was evident between the type of the allele present in the studied polymorphisms, p value = 0.000040. Moreover, the minor allele frequency (MAF) of the studied variants rs751402 and rs1047768 were similar to those of African and European populations, respectively. Results of this study have concluded that ERCC5 variants did not affect the clinical outcome of platinum-based chemotherapy in NSCLC. A significant coinheritance was found between the two variants of ERCC5. Moreover, the similarity between the MAF of the studied variants and the African or European population can guide future research when extrapolating data from African European populations to their Egyptian counterparts.

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Section: Discussionsupporting

confidence: 93%

“…On the other hand, for the rs1047768, the association was found in the general and recessive model representing a link with the C allele (major allele). Rulli et al found a similar association between ERCC1 (rs11615) genetic variants and the histologic subtypes of NSCLC [ 34 ].…”

Section: Discussionmentioning

confidence: 97%

Variants of ERCC5 and the outcome of platinum-based regimens in non-small cell lung cancer: a prospective cohort study

et al. 2022

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“…However, few studies have investigated the implication of the NER biological pathway and ERCC1 polymorphisms, including rs3212986[ 20 , 21 ], in hepatocarcinogenesis, and no data are available in Caucasian populations. The ERCC1 rs3212986 variant, located in the 3’ untranslated region (3’UTR) of the gene, is thought to increase transcript stability, although further biochemical studies are required to clarify the effect of this polymorphism on gene transcription and protein translation[ 22 , 23 ]. Based on our data, we inferred that the rs3212986 variant allele was associated with elevated ERCC1 expression and/or activity, which could lead to enhanced protection against the accumulation of mutagenic DNA lesions, and consequently, against hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Genetic biomarkers for hepatocellular cancer risk in a caucasian population

Mattia

Cecchin

Polesel

et al. 2017

WJG

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AIMTo uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma (HCC) susceptibility in Caucasians.METHODSThe present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two, independent, HCC-free, age/sex-matched control groups. The HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver transplantation. The first control group comprised 167 patients that were matched to the HCC cohort for the percentage of hepatitis B (HBV) and/or hepatitis C (HCV) infections. A second control group included 192 virus-free, healthy individuals that were used to evaluate the generalizability of the identified predictive markers. All cases and controls were Caucasian. The three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related pathways. The study end-point was to assess the association between genetic variants and HCC onset.RESULTSFive genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/HCV. According to a dominant model, reduced HCC risk was associated with three polymorphisms: ERCC1 rs3212986 (OR = 0.46, 95%CI: 0.30-0.71, P = 0.0005), GST-P1 rs1138272 (OR = 0.41, 95%CI: 0.21-0.81, P = 0.0097), and CYP17A1 rs743572 (OR = 0.50, 95%CI: 0.31-0.79, P = 0.0032). Conversely, according to a recessive model, increased HCC risk was associated with two polymorphisms: XRCC3 rs1799794 (OR = 3.70, 95%CI: 1.02-13.39, P = 0.0461) and ABCB1 rs1128503 (OR = 2.06, 95%CI: 1.18-3.61, P = 0.0111). These associations remained significant in a subgroup analysis, where patients were stratified according to viral status (HBV- or HCV-positive serology). Two variants exhibited a serology-specific effect: ABCB1 rs1128503 (OR = 4.18, 95%CI: 1.55-11.29, P = 0.0048) showed an effect in the HBV-positive subgroup; and ERCC1 rs3212986 (OR = 0.33, 95%CI: 0.18-0.60, P = 0.0003) showed an effect in the HCV-positive subgroup. Among the five markers identified, ERCC1 rs3212986 (OR = 0.43, P < 0.0001) and CYP17A1 rs743572 (OR = 0.73, P = 0.0310) had a different distribution in patients with HCC compared to healthy individuals. With a recursive partitioning approach, we also demonstrated that significant gene-gene interactions between ERCC1 rs3212986, CYP17A1 rs743572, GST-P1 rs1138272, and the previously described UGT1A7*3 predictive marker, played a role in the complex trait of HCC susceptibility.CONCLUSIONWe identified five polymorphisms and interactions that contributed crucially to predicting HCC risk. These findings represented an important step towards improving HCC diagnosis and management.

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“…In the literature, there have been several ERCC1 SNPs examined for their cancer risk and s11615 and rs3212986 have been the most frequently studied. For example, identifying the ERCC1 rs11615 genotype may help in predicting a positive or poor outcome of platinum-based chemotherapy for patients with colorectal (29), advanced gastric (30-32) and breast cancer (33) as well as testicular germ cell tumors (34), ovarian (35,36), esophageal (37), and most importantly, non-small cell lung cancer (17)(18)(19)(20). Molecular studies consistently provided evidence showing that ERCC1 rs11615 T allele is associated with relatively lower expression of ERCC1 at both the mRNA and protein levels; however, its role as a predictive marker for cancer therapy is controversial (38-42).…”

Section: Discussionmentioning

confidence: 99%

“…From late 1990s, evidence have been accumulating showing that in cancers, such as ovarian and gastric cancer, the expression level of ERCC1 may be a useful marker for clinical drug resistance for those patients with platinum-based chemo-treatments (16). In addition, it has also been suggested that ERCC1 downregulation is associated with increased chemotherapeutic sensitivity and, thus, considered as a predictive marker for lung patients receiving platinum-based chemotherapy (17)(18)(19)(20). However, ERCC1 genotype is seldom evaluated as a predictor for lung cancer risk.…”

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confidence: 99%

The Significant Interaction of Excision Repair Cross-complementing Group 1 Genotypes and Smoking to Lung Cancer Risk

Chen

Shen

et al. 2020

Cancer Genomics Proteomics

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Background: The study aims to evaluate the contribution of excision repair cross-complementing group 1 (ERCC1), which plays an important role in genome integrity maintenance, to lung cancer risk. Materials and Methods: ERCC1 rs11615 and rs3212986 genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and their association with lung cancer risk was examined among 358 lung cancer patients and 716 controls. Results: The proportions of CC, CT and TT for the rs11615 genotype were 43.6%, 41.6% and 14.8% in the case group and 50.0%, 41.1% and 8.9% in the control group, respectively (p for trend=0.0082). Allelic analysis showed that ERCC1 rs11615 T-allele carriers have a 1.32-fold higher risk of lung cancer than wild-type C-allele carriers [95%confidence interval (CI)=1.09-1.60, p=0.0039]. In addition, a significant interaction between the rs11615 genotype and smoking status was observed. Conclusion: The T allele of ERCC1 rs11615 jointly with smoking habits may contribute to a higher lung cancer risk in Taiwan. According to the most recent report on cancer incidence and mortality by the International Agency for Research on Cancer, lung cancer has remained as the leading cause of cancer deaths all over the world (1). An estimated 2.1 million new lung cancer cases and 1.8 million cancer-related deaths occurred worldwide in 2018 (1). The rapidly increasing cases and the high death rate have urged us to look for effective marker(s) for the prediction of the risk of lung cancer, the outcome of the prognosis and the responsiveness of patient drug treatment. The initiation and development of lung cancer is related to multiple exogenous and endogenous factors including behavioral, environmental and genetic discrepancies, among which the consumption of cigarettes is the most significant factor to be associated with lung cancer risk (2). On the other hand, the fact that about 10% to 25% of lung cancer patients are non-smokers worldwide indicates that the individual genomic influences also play a critical part for personal lung cancer etiology (3). In Taiwan, the incidence and mortality of lung cancer has been ranked on the third and first place, respectively, among different types of cancer, for several years (4). Although several biomarkers for the early detection of lung cancer are being examined during recent years (5-11), the continuous search for effective clinically practical markers and the undermining mechanisms is still largely ongoing. Our genome is regularly and frequently damaged by various kinds of endogenous and exogenous mutagens and the DNA repair systems play a vital role in protecting it from irreversible mutations that can lead to carcinogenesis (12, 13). Concerning non-small cell lung cancer, genomic instability was 571 This article is freely accessible online.

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DNA Repair Gene Polymorphisms in Non-Small-Cell Lung Cancer Patients Treated with First-Line Platinum-Containing Chemotherapy

Abstract: The findings suggest that the investigated SNPs do not make any significant contribution to the outcome of NSCLC.

Cited by 4 publications

References 41 publications

Variants of ERCC5 and the outcome of platinum-based regimens in non-small cell lung cancer: a prospective cohort study

Variants of ERCC5 and the outcome of platinum-based regimens in non-small cell lung cancer: a prospective cohort study

Genetic biomarkers for hepatocellular cancer risk in a caucasian population

The Significant Interaction of Excision Repair Cross-complementing Group 1 Genotypes and Smoking to Lung Cancer Risk

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