| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Impact of single-nucleotide polymorphisms in DNA repair pathway genes on response to chemoradiotherapy in rectal cancer patients: Results from ACCORD-12/PRODIGE-2 phase III trial |
| Creator | Boige et al. |
| Author | Valérie Boige |
| Author | Caroline Mollevi |
| Author | Sophie Gourgou |
| Author | David Azria |
| Author | Jean-François Seitz |
| Author | Marc Vincent |
| Author | Ludovic Bigot |
| Author | Beata Juzyna |
| Author | Isabelle Miran |
| Author | Jean-Pierre Gerard |
| Author | Pierre Laurent-Puig |
| Abstract | We examined whether 66 germline single-nucleotide polymorphisms (SNPs) in 10 candidate genes would predict clinical outcome in 316 patients with resectable locally advanced rectal cancer (LARC) enrolled in the ACCORD-12 phase III trial who were randomly treated with preoperative radiotherapy plus capecitabine (CAP45; n = 155) or dose-intensified radiotherapy plus capecitabine and oxaliplatin (CAPOX50; n = 161). The primary endpoint was tumor response according to the Dworak score. Multivariate logistic regression models adjusted on treatment arm and T stage determined the SNPs prognostic and predictive values for tumor response. In univariate analysis, five SNPs in ERCC2, XPA, MTHFR and ERCC1 were associated with the Dworak score in the CAPOX50 arm. In the overall population, interaction with treatment arm was significant for ERCC2 rs1799787 (pinteraction = 0.05) and XPA rs3176683 (pinteraction = 0.008), suggesting a predictive effect for response to oxaliplatin-based chemoradiotherapy (CRT). All but XPA rs3176683 had a prognostic effect on tumor response. In a multivariate model, interaction remained significant for XPA rs3176683 ([OR 7.33, 95% CI 1.40-38.23], pinteraction = 0.018) and the prognostic effect significant for ERCC2 rs1799787 ([OR 0.55, 95%CI 0.32-0.93], p = 0.027) and ERCC1 rs10412761 ([OR 0.57, 95%CI 0.34-0.98], p = 0.042). Patients with the T/G haplotype of rs1799787 and rs10412761 had a 60% decrease in odds of response (p? |
| Publication | International Journal of Cancer |
| Date | May 20, 2019 |
| Journal Abbr | Int. J. Cancer |
| Language | eng |
| DOI | 10.1002/ijc.32417 |
| ISSN | 1097-0215 |
| Short Title | Impact of single-nucleotide polymorphisms in DNA repair pathway genes on response to chemoradiotherapy in rectal cancer patients |
| Library Catalog | PubMed |
| Extra | PMID: 31107542 |
| Tags | clinic, Dworak score, ERCC1, ERCC2, oxaliplatin, pathological response, pharmacogenetics, single-nucleotide polymorphism, XPA |
| Date Added | 2019/06/04 - 15:57:14 |
| Date Modified | 2019/12/10 - 17:06:48 |
| Notes and Attachments | PubMed entry (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
