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Genetic polymorphisms in SLC23A2 as predictive biomarkers of severe acute toxicities after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.

Minegaki T, Kuwahara A, Yamamori M, Nakamura T, Okuno T, Miki I, Omatsu H, Tamura T, Hirai M, Azuma T, Sakaeda T, Nishiguchi K - Int J Med Sci (2014)

Bottom Line: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively).The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively.Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.

View Article: PubMed Central - PubMed

Affiliation: 1. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.

ABSTRACT

Objective: Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell carcinoma (ESCC); however, inter-individual variations in clinical outcomes have yet to be investigated. In the present study, single nucleotide polymorphisms (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the predictive values for the clinical response, severe acute toxicities, and long-term survival were assessed.

Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course being repeated after a 2-week interval. The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were evaluated.

Results: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively.

Conclusions: Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.

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Related in: MedlinePlus

Association between the SLC23A2 genotypes of rs2681116 and rs13037458 and long-term survival in 49 patients following treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy. Long-term survival was possibly associated with these genotypes (p=0.142 for rs2681116 and p=0.056 for rs13037458; the log-rank test).
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Figure 1: Association between the SLC23A2 genotypes of rs2681116 and rs13037458 and long-term survival in 49 patients following treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy. Long-term survival was possibly associated with these genotypes (p=0.142 for rs2681116 and p=0.056 for rs13037458; the log-rank test).

Mentions: Table 1 summarizes the data on associations between 5 SLC23A2 SNPs and the clinical response. No significant correlations were observed between the genotypes examined and the clinical response; however, rs2681116 (p=0.144) and rs13037458 (p=0.085) had a tendency to associate with. As shown in Figure 1, these 2 SNPs also showed a tendency to predict long-term survival (p=0.142 for rs2681116, p=0.056 for rs13037458). Table 2 lists associations with severe acute leukopenia, stomatitis, and cheilitis. rs4987219 and rs1110277 significantly correlated with leukopenia (p=0.025) and stomatitis (p=0.019), respectively.


Genetic polymorphisms in SLC23A2 as predictive biomarkers of severe acute toxicities after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.

Minegaki T, Kuwahara A, Yamamori M, Nakamura T, Okuno T, Miki I, Omatsu H, Tamura T, Hirai M, Azuma T, Sakaeda T, Nishiguchi K - Int J Med Sci (2014)

Association between the SLC23A2 genotypes of rs2681116 and rs13037458 and long-term survival in 49 patients following treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy. Long-term survival was possibly associated with these genotypes (p=0.142 for rs2681116 and p=0.056 for rs13037458; the log-rank test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3936025&req=5

Figure 1: Association between the SLC23A2 genotypes of rs2681116 and rs13037458 and long-term survival in 49 patients following treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy. Long-term survival was possibly associated with these genotypes (p=0.142 for rs2681116 and p=0.056 for rs13037458; the log-rank test).
Mentions: Table 1 summarizes the data on associations between 5 SLC23A2 SNPs and the clinical response. No significant correlations were observed between the genotypes examined and the clinical response; however, rs2681116 (p=0.144) and rs13037458 (p=0.085) had a tendency to associate with. As shown in Figure 1, these 2 SNPs also showed a tendency to predict long-term survival (p=0.142 for rs2681116, p=0.056 for rs13037458). Table 2 lists associations with severe acute leukopenia, stomatitis, and cheilitis. rs4987219 and rs1110277 significantly correlated with leukopenia (p=0.025) and stomatitis (p=0.019), respectively.

Bottom Line: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively).The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively.Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.

View Article: PubMed Central - PubMed

Affiliation: 1. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.

ABSTRACT

Objective: Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell carcinoma (ESCC); however, inter-individual variations in clinical outcomes have yet to be investigated. In the present study, single nucleotide polymorphisms (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the predictive values for the clinical response, severe acute toxicities, and long-term survival were assessed.

Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course being repeated after a 2-week interval. The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were evaluated.

Results: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively.

Conclusions: Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.

Show MeSH
Related in: MedlinePlus