Association Between Rs3212986 and Rs1799793 and OS in Patients With Advanced Esophageal Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2019 Mar 9

PMID 30847299

Citations 5

Authors

Elisa Boldrin

Sandro Malacrida

Enrica Rumiato

Giorgio Battaglia

Alberto Ruol

Alberto Amadori

Daniela Saggioro

Affiliations

Soon will be listed here.

Abstract

Esophageal cancer (EC) is a very aggressive tumor, and no reliable prognostic markers exist especially for resectable advanced neoplasia. The principal aim of this study was to investigate the association of germline polymorphisms in nucleotide excision repair (NER) pathway genes with the overall survival (OS) of patients with advanced EC. As a second aim, we also studied the association of NER gene variants with response to cisplatin-based chemotherapy. Among the EC patients referred to our Institution between 2004 and 2012, we selected a cohort of 180 patients diagnosed with a clinical tumor stage ranging from IIB and IVA. Patients were genotyped for four NER variants, two in the (rs11615 and rs3212986) and two in the (rs1799793 and rs13181) genes. Kaplan-Meier analyses and Cox proportional hazards model were used to evaluate the associations of the selected variants with OS; association with response to neoadjuvant therapy was investigated using logistic regression. Results showed that the rs3212986 and the rs1799793 were significantly associated with shorter OS. On the contrary, response association analysis displayed that, while rs11615 and rs3212986 in were associated with response, both variants were not. By creating survival prediction models, we showed that the rs3212986 and the rs1799793 have a better predictability of the tumor stage alone. Furthermore, they were able to improve the power of the clinical model (AUC = 0.660 vs. AUC = 0.548, = 0.004). In conclusion, our results indicate that the rs3212986 and the rs1799793 could be used as surrogate markers for a better stratification of EC patients with advanced resectable tumor.

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References

Chen P, Wiencke J, Aldape K, Miike R, Kelsey K, Lee M . Association of an ERCC1 polymorphism with adult-onset glioma. Cancer Epidemiol Biomarkers Prev. 2000; 9(8):843-7. View

Spitz M, Wu X, Wang Y, Wang L, Shete S, Amos C . Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res. 2001; 61(4):1354-7. View

Seker H, Butkiewicz D, Bowman E, Rusin M, Hedayati M, Grossman L . Functional significance of XPD polymorphic variants: attenuated apoptosis in human lymphoblastoid cells with the XPD 312 Asp/Asp genotype. Cancer Res. 2001; 61(20):7430-4. View

Goode E, Ulrich C, Potter J . Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002; 11(12):1513-30. View

Neumann A, Sturgis E, Wei Q . Nucleotide excision repair as a marker for susceptibility to tobacco-related cancers: a review of molecular epidemiological studies. Mol Carcinog. 2005; 42(2):65-92. DOI: 10.1002/mc.20069. View

Tudek B . Base excision repair modulation as a risk factor for human cancers. Mol Aspects Med. 2007; 28(3-4):258-75. DOI: 10.1016/j.mam.2007.05.003. View

Wolfe K, Wickliffe J, Hill C, Paolini M, Ammenheuser M, Abdel-Rahman S . Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics. 2007; 17(11):897-905. DOI: 10.1097/FPC.0b013e3280115e63. View

Menashe I, Rosenberg P, Chen B . PGA: power calculator for case-control genetic association analyses. BMC Genet. 2008; 9:36. PMC: 2387159. DOI: 10.1186/1471-2156-9-36. View

Pan J, Lin J, Izzo J, Liu Y, Xing J, Huang M . Genetic susceptibility to esophageal cancer: the role of the nucleotide excision repair pathway. Carcinogenesis. 2009; 30(5):785-92. PMC: 2675653. DOI: 10.1093/carcin/bgp058. View

10.

Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A . Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009; 30(7):1073-81. DOI: 10.1093/carcin/bgp127. View

11.

Bradbury P, Kulke M, Heist R, Zhou W, Ma C, Xu W . Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes. Pharmacogenet Genomics. 2009; 19(8):613-25. PMC: 3085844. DOI: 10.1097/FPC.0b013e32832f3010. View

12.

Wheeler H, Gamazon E, Stark A, ODonnell P, Gorsic L, Huang R . Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations. Pharmacogenomics J. 2011; 13(1):35-43. PMC: 3370147. DOI: 10.1038/tpj.2011.38. View

13.

Duan X, Gong H, Zeng X, Ni X, Yan Y, Chen W . Association between XPD Asp312Asn polymorphism and esophageal cancer susceptibility: a meta-analysis. Asian Pac J Cancer Prev. 2012; 13(7):3299-303. DOI: 10.7314/apjcp.2012.13.7.3299. View

14.

Rugge M, Fassan M, Cavallin F, Cavallini F, Zaninotto G . Re: Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst. 2012; 104(22):1771-2. DOI: 10.1093/jnci/djs426. View

15.

Wheeler H, Maitland M, Dolan M, Cox N, Ratain M . Cancer pharmacogenomics: strategies and challenges. Nat Rev Genet. 2012; 14(1):23-34. PMC: 3668552. DOI: 10.1038/nrg3352. View

16.

Abdulrahman W, Iltis I, Radu L, Braun C, Maglott-Roth A, Giraudon C . ARCH domain of XPD, an anchoring platform for CAK that conditions TFIIH DNA repair and transcription activities. Proc Natl Acad Sci U S A. 2013; 110(8):E633-42. PMC: 3581935. DOI: 10.1073/pnas.1213981110. View

17.

Paszkowska-Szczur K, Scott R, Serrano-Fernandez P, Mirecka A, Gapska P, Gorski B . Xeroderma pigmentosum genes and melanoma risk. Int J Cancer. 2013; 133(5):1094-100. DOI: 10.1002/ijc.28123. View

18.

McCullough L, Santella R, Cleveland R, Millikan R, Olshan A, North K . Polymorphisms in DNA repair genes, recreational physical activity and breast cancer risk. Int J Cancer. 2013; 134(3):654-63. PMC: 3830595. DOI: 10.1002/ijc.28383. View

19.

Rumiato E, Cavallin F, Boldrin E, Cagol M, Alfieri R, Basso D . ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy. Pharmacogenet Genomics. 2013; 23(11):597-604. DOI: 10.1097/FPC.0b013e3283653afc. View

20.

Li Y, Liu Z, Liu H, Wang L, Tan D, Ajani J . ERCC1 and ERCC2 variants predict survival in gastric cancer patients. PLoS One. 2013; 8(9):e71994. PMC: 3759385. DOI: 10.1371/journal.pone.0071994. View