- 作者：David Pá ; ez M.D.&lowast ; ; ; dpaez@santpau.cat ; Juliana Salazar Ph.D.&dagger ; ; ; &Dagger ; ; Laia Paré ; M.Sc.&dagger ; ; ; &Dagger ; ; Lourdes Pertriz M.D.§ ; ; Eduardo Targarona M.D.¶ ; ; Elisabeth del Rio B.Sc.&dagger ; ; ; &Dagger ; ; Agusti Barnadas Ph.D. ; M.D.&lowast ; ; Eugenio Marcuello M.D.&lowast ; ; Montserrat Baiget Ph.D.&dagger ; ; ; &Dagger ;
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2011
- 出版时间：1 December 2011
- 年：2011
- 卷：81
- 期：5
- 页码：1319-1327
- 全文大小：278 K
Purpose
Several studies have been performed to evaluate the usefulness of neoadjuvant treatment using oxaliplatin and fluoropyrimidines for locally advanced rectal cancer. However, preoperative biomarkers of outcome are lacking. We studied the polymorphisms in thymidylate synthase, epidermal growth factor receptor, glutathione S-transferase pi 1 (GSTP1), and several DNA repair genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 128 rectal cancer patients treated with preoperative chemoradiotherapy.Methods and Materials
Blood samples were obtained from 128 patients with Stage II-III rectal cancer. DNA was extracted from the peripheral blood nucleated cells, and the genotypes were analyzed by polymerase chain reaction amplification and automated sequencing techniques or using a 48.48 dynamic array on the BioMark system. The germline polymorphisms studied were thymidylate synthase, (VNTR/5¡äUTR, 2R G>C single nucleotide polymorphism [SNP], 3R G>C SNP), epidermal growth factor receptor (Arg497Lys), mlns="""">GSTP1 (Ile105val), excision repair cross-complementing 1 (Asn118Asn, 8092C>A, 19716G>C), X-ray repair cross-complementing group 1 (XRCC1) (Arg194Trp, Arg280His, Arg399Gln), and xeroderma pigmentosum group D (Lys751Gln). The pathologic response, pathologic regression, progression-free survival, and overall survival were evaluated according to each genotype.
Results
The ?/? thymidylate synthase genotype was associated with a greater response rate (pathologic complete remission and microfoci residual tumor, 59 % in ?/? vs. 35 % in ?/? and ?/?; mlns="""">p?= .013). For the thymidylate synthase genotype, the median progression-free survival was 103 months for the ?/? patients and 84 months for the ?/? and ?/? patients (mlns="""">p?= .039). For XRCC1 Arg399Gln SNP, the median progression-free survival was 101 months for the G/G, 78 months for the G/A, and 31 months for the A/A patients (mlns="""">p?= .048).
Conclusions
The thymidylate synthase genotype and XRCC1 Arg399Gln polymorphism might help to identify Stage II-III rectal cancer patients with a better outcome after preoperative concomitant chemoradiotherapy.