Polymorphism of FGD4 and Myelosuppression in Patients with Esophageal Squamous Cell Carcinoma

Abstract

Background: Chemotherapy-related adverse events may restrain taxane/cisplatin administration as a regimen for patients with esophageal squamous cell carcinoma. Genetic polymorphisms may contribute to adverse event susceptibility. Method & results: The authors genotyped ten SNPs from five genes (rs1045642, rs2032582 and rs3213619 of ABCB1; rs2231137 and rs2231142 of ABCG2; rs246221 of ABCC1; rs3740066 of ABCC2; and rs10771973, rs12296975 and rs1239829 of FGD4) in 219 patients with esophageal squamous cell carcinoma treated with taxane/cisplatin. Patients with severe toxicities were compared with those with minor or no adverse events by unconditional logistic regression models and semi-Bayesian shrinkage. After adjustment for age and sex, with the null prior, FGD4 rs1239829 was statistically significantly related to grade 3–4 leukopenia (odds ratio [95% CI] in dominant model = 1.77 [1.04–3.03]). Conclusion: The minor allele of FGD4 rs1239829 was related to grade 3–4 leukopenia in patients with esophageal squamous cell carcinoma treated with taxane/cisplatin, with unclear biological mechanism.

Association between polymorphisms of ABCB1 and prognosis in esophageal squamous cell carcinoma patients treated with taxane

“…Seven SNPs (rs1045642, rs2032582, and rs3213619 of ABCB1; rs2231137 and rs2231142 of ABCG2; and ABCC1 rs246221 and ABCC2 rs3740066) were decided for analysis. Selected SNPs were genotyped in all 227 patients simultaneously with a customized MassARRAY™ matrix‐assisted laser desorption ionization–time of flight system (Sequenom, Inc.) that was operated by Precision Medicine Biological Technology (Wuxi) Co., Ltd in China, as described previously 19 . The corresponding primer information of each SNP is provided in the Supporting information (Table S2).…”

“…Selected SNPs were genotyped in all 227 patients simultaneously with a customized Mass-ARRAY™ matrix-assisted laser desorption ionization-time of flight system (Sequenom, Inc.) that was operated by Precision Medicine Biological Technology (Wuxi) Co., Ltd in China, as described previously. 19 The corresponding primer information of each SNP is provided in the Supporting information (Table S2). Approximately 5% of the samples were replicated for quality control.…”

“…The ABC superfamily functions in substance distribution and transportation across the cellular membrane 17 ; thus, most studies have focused on the relation of their genetic variations and anticancer treatment response and toxicities 18,19 . For example, Wang et al 18 .…”

“…16 The ABC superfamily functions in substance distribution and transportation across the cellular membrane 17 ; thus, most studies have focused on the relation of their genetic variations and anticancer treatment response and toxicities. 18,19 For example, Wang et al 18 showed that, in radioresistant ESCC cells, the expression of both ABCC1 mRNA and protein was higher than that in their counterparts, and upregulation of ABCB1 expression together with ionization radiation induced drug resistance. Nevertheless, our previously published study found no relationship between ABC family members and taxane toxicity in ESCC patients.…”

“…Nevertheless, our previously published study found no relationship between ABC family members and taxane toxicity in ESCC patients. 19 In terms of prognosis, there were no studies on ABC family polymorphisms and ESCC survival, and a few studies on other cancer prognoses, such as lung cancer, 20,21 prostate cancer, 22 primary hepatocellular carcinoma, 23 normal karyotype acute myeloid leukemia, 24 nasopharyngeal carcinoma, 25 and head and neck cancer, 26 had contradictory conclusions.…”