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- W618903640 abstract "4047 Background: CD44 is a transmembrane glycoprotein serving as receptor of hyaluronan and osteopontin, is associated with adhesion and metastasis in gastrointestinal carcinomas. Moreover, a gastric cancer stem cell population with CD44 as their defined surface marker has been identified showing increased resistance for chemotherapy- or radiation-induced cell death. High CD44 protein expression has been associated with poor prognosis in GA. We tested the hypothesis whether germline variations involved in the CD44 pathway will predict clinical outcome in patients with localized GA. Methods: Either blood or FFPE tissues specimens were obtained from 137 patients (54 females and 83 males; median age = 55 yrs; range = 21-85 yrs) with localized GA at University of Southern California (n = 105) and Memorial Sloan-Kettering Cancer Center medical facilities (n = 32). The median follow-up was 3.3 years. Sixty-one of 137 patients (45%) had tumor recurrence, with a probability of 3-year recurrence of 52%. Genomic DNA was isolated from peripheral blood or FFPE tissues and germline variants within the CD44 (rs8193, rs187116, rs4755392, rs7116432), osteopontin (rs9138, rs1126616) and hyaluronan (rs4123220, rs1057308) genes were determined by PCR-RFLP technique. Results: The G allele (GG; AG) at the CD44 +4883G>A gene locus (rs187116) and the A allele (AA; AG) at the CD44 +779G>A gene locus (rs7116432) had a significantly shorter median TTR of 2.1 years compared to 7.0 years (p = 0.036, log-rank test) and a median OS of 2.2 years compared to 7.0 years (p = 0.045, log-rank test), respectively in univariate analysis. After adjusting for clinical parameters, patients harboring 0 favorable alleles of the tested CD44 SNPs had a significantly worse TTR (RR: 2.41; adjusted p value = 0.016) and OS (RR: 2.74; adjusted p value = 0.019) in the multivariable analysis. No statistical significant association was found between TTR or OS and the other tested germline variants. Conclusions: For the first time, this study identified germline variants within the CD44 gene as independent prognostic markers in localized GA. Our exploratory data warrant future confirmatory trials. No significant financial relationships to disclose." @default.
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- W618903640 date "2010-05-20" @default.
- W618903640 modified "2023-10-17" @default.
- W618903640 title "Association of germline polymorphisms in genes involved in the CD44 pathway and clinical outcome in localized gastric adenocarcinoma (GA)." @default.
- W618903640 doi "https://doi.org/10.1200/jco.2010.28.15_suppl.4047" @default.
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