EGFR intron-1 CA repeat polymorphism is a predictor of relapse and survival in complete resected only surgically treated esophageal cancer

TY - JOUR

T1 - EGFR intron-1 CA repeat polymorphism is a predictor of relapse and survival in complete resected only surgically treated esophageal cancer

AU - Vashist, Yogesh K

AU - Trump, Florian

AU - Gebauer, Florian

AU - Kutup, Asad

AU - Güngör, Cenap

AU - Kalinin, Viacheslav

AU - Muddasar, Rather

AU - Vettorazzi, Eik

AU - Yekebas, Emre F

AU - Brandt, Burkhard

AU - Pantel, Klaus

AU - Izbicki, Jakob R

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Basal transcription regulation of the epidermal growth factor receptor is dependent upon a CA simple sequence repeat polymorphism in the intron-1 (CA-SSR-1). Here, we evaluate the role of CA-SSR-1 in complete resected esophageal cancer (EC) patients without neoadjuvant or adjuvant treatment. Genomic DNA was extracted from peripheral blood leukocytes of 241 patients. To determine the number of the CA repeats in the CA-SSR-1, DNA was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters and clinical outcome. Three genotypes were defined based on cut-off points for short allele (S) with ≤18 and long allele (L) >18 CA repeats. A steadily increasing risk was evident between LL, SL, and SS genotype for larger tumor size, presence of lymph node metastases, and disseminated tumor cells in bone marrow as well as tumor recurrence (P < 0.001, chi-square test). A gradual decrease in disease-free and overall survival (OS) was present among LL, SL, and SS patients (P < 0.001, log-rank test). The different outcomes were also evident in nodal status and histological type adjusted subgroup analyses. CA-SSR-1 was identified as the strongest independent prognosticator of tumor recurrence and OS (P < 0.001, Cox regression analysis). CA-SSR-1 is a strong predictive factor for tumor recurrence and overall survival in patients with complete resected esophageal cancer without neoadjuvant or adjuvant therapy.

AB - Basal transcription regulation of the epidermal growth factor receptor is dependent upon a CA simple sequence repeat polymorphism in the intron-1 (CA-SSR-1). Here, we evaluate the role of CA-SSR-1 in complete resected esophageal cancer (EC) patients without neoadjuvant or adjuvant treatment. Genomic DNA was extracted from peripheral blood leukocytes of 241 patients. To determine the number of the CA repeats in the CA-SSR-1, DNA was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters and clinical outcome. Three genotypes were defined based on cut-off points for short allele (S) with ≤18 and long allele (L) >18 CA repeats. A steadily increasing risk was evident between LL, SL, and SS genotype for larger tumor size, presence of lymph node metastases, and disseminated tumor cells in bone marrow as well as tumor recurrence (P < 0.001, chi-square test). A gradual decrease in disease-free and overall survival (OS) was present among LL, SL, and SS patients (P < 0.001, log-rank test). The different outcomes were also evident in nodal status and histological type adjusted subgroup analyses. CA-SSR-1 was identified as the strongest independent prognosticator of tumor recurrence and OS (P < 0.001, Cox regression analysis). CA-SSR-1 is a strong predictive factor for tumor recurrence and overall survival in patients with complete resected esophageal cancer without neoadjuvant or adjuvant therapy.

U2 - 10.1007/s11523-013-0260-2

DO - 10.1007/s11523-013-0260-2

M3 - SCORING: Journal article

C2 - 23377570

VL - 9

SP - 43

EP - 52

JO - TARGET ONCOL

JF - TARGET ONCOL

SN - 1776-2596

IS - 1

ER -