General Information of Drug Transporter (DT)
DT ID	DTD0244 Transporter Info
Gene Name	SLC28A1
Protein Name	Concentrative nucleoside transporter 1
Gene ID	9154
UniProt ID	O00337
Genetic Polymorphisms of DT (GPD)
Genetic Polymorphism	rs2242046
Site of GPD	chr15:84935498 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A / G>T
Minor Allele Frequency	A=0.2081/1042 (Global)
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           3 Drugs in Total
Gemcitabine	Drug Info	Non-Small-Cell Lung Carcinoma	Correlated with the decreased hematologic toxicity risk in patients (compare with genotypes AA + AG)		[ 1]
Gemcitabine	N.A.	Nephrotoxicity	Genotype GG is associated with decreased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AG.		[ 1]
Gemcitabine	N.A.	Non-small Cell Lung Carcinoma	Genotype GG is associated with decreased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AG.		[ 1]
Allele A	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Gemcitabine	N.A.	Cardiotoxicity	Allele A is not associated with clearance of gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to allele G.		[ 2]
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Gemcitabine	N.A.	Non-small Cell Lung Carcinoma	Patients with the AA genotype and non-small-cell lung cancer may have an increased risk of hematologic toxicity when treated with gemcitabine as compared to patients with the GG genotype. Other genetic and clinical factors may also influence risk of hematologic toxicity.		[ 1]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Gemcitabine	N.A.	Non-small Cell Lung Carcinoma	Patients with the AG genotype and non-small-cell lung cancer may have an increased risk of hematologic toxicity when treated with gemcitabine as compared to patients with the GG genotype. Other genetic and clinical factors may also influence risk of hematologic toxicity.		[ 1]
Genetic Polymorphism	rs2290271
Site of GPD	chr15:84904404 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	A>C
Minor Allele Frequency	C=0.4383/2195 (Global)
Allele C	Click to Show/Hide the Full List of Affected Drugs:           7 Drugs in Total
Daunorubicin	Drug Info	Neoplasm	Irrelevant to the likelihood of cardiotoxicity in patients (compare with Allele A)		[ 3]
Doxorubicin	Drug Info	Neoplasm	Irrelevant to the likelihood of cardiotoxicity in patients (compare with Allele A)		[ 3]
Anthracyclines And Related Substances	N.A.	Nephrotoxicity	Allele C is associated with decreased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to allele A.		[ 4]
Daunorubicin	N.A.	Cardiotoxicity	Allele C is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele A.		[ 3]
Doxorubicin	N.A.	Cardiotoxicity	Allele C is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele A.		[ 3]
Anthracyclines And Related Substances	N.A.	Neutropenia	Allele C is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele A.		[ 3]
Anthracyclines	N.A.	Neoplasm	Correlated with the decreased likelihood of cardiotoxicity in patients (compare with Allele A)		[ 4]
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Anthracyclines And Related Substances	N.A.	Neutropenia	Patients with genotype AA may have increased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to patients with genotype CC or AC, although this is contradicted in one study. Other genetic and clinical factors may also influence the toxicity to anthracyclines.		[ 4]
Genotype AC	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Anthracyclines And Related Substances	N.A.	Neutropenia	Patients with genotype AC may have decreased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to patients with genotype AA, although this is contradicted in one study. Other genetic and clinical factors may also influence the toxicity to anthracyclines.		[ 4]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Anthracyclines And Related Substances	N.A.	Neutropenia	Patients with genotype CC may have decreased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to patients with genotype AA, although this is contradicted in one study. Other genetic and clinical factors may also influence the toxicity to anthracyclines.		[ 4]
Genetic Polymorphism	rs2305364
Site of GPD	chr15:84909044 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>C
Allele T	Click to Show/Hide the Full List of Affected Drugs:           8 Drugs in Total
Daunorubicin	Drug Info	Neoplasm	Irrelevant to the likelihood of cardiotoxicity in patients (compare with allele C)		[ 3]
Doxorubicin	Drug Info	Neoplasm	Irrelevant to the likelihood of cardiotoxicity in patients (compare with allele C)		[ 3]
Anthracyclines And Related Substances	N.A.	Nephrotoxicity	Allele T is associated with increased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to allele C.		[ 4]
Daunorubicin	N.A.	Cardiotoxicity	Allele T is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele C.		[ 3]
Doxorubicin	N.A.	Cardiotoxicity	Allele T is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele C.		[ 3]
Anthracyclines And Related Substances	N.A.	Neoplasms	Allele T is associated with increased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to allele C.		[ 4]
Anthracyclines And Related Substances	N.A.	Neoplasms	Allele T is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele C.		[ 3]
Anthracyclines	N.A.	Neoplasm	Correlated with the increased likelihood of cardiotoxicity in patients (compare with allele C)		[ 4]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Anthracyclines And Related Substances	N.A.	Neoplasms	Patients with the CC genotype may have decreased likelihood of cardiotoxicity when exposed to anthracyclines for pediatric cancer as compared to patients with the CT or TT genotype, although this is contradicted in one study. Other genetic and clinical factors may also influence risk for cardiotoxicity.		[ 4]
Genotype CT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Anthracyclines And Related Substances	N.A.	Neoplasms	Patients with the CT genotype may have decreased likelihood of cardiotoxicity when exposed to anthracyclines for pediatric cancer as compared to patients with the TT genotype and increased likelihood as compared to patients with the CC genotype, although this is contradicted in one study. Other genetic and clinical factors may also influence risk for cardiotoxicity.		[ 4]
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Anthracyclines And Related Substances	N.A.	Neoplasms	Patients with the TT genotype may have an increased likelihood of cardiotoxicity when exposed to anthracyclines for pediatric cancer as compared to patients with the CT or CC genotypes, although this is contradicted in one study. Other genetic and clinical factors may also influence risk for cardiotoxicity.		[ 4]
Genetic Polymorphism	rs2290272
Site of GPD	chr15:84904200 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A / G>C
Minor Allele Frequency	G=0.6210/1228 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Capecitabine	N.A.	Nephrotoxicity	Allele A is not associated with metabolism of capecitabine in people with Breast Neoplasms as compared to allele G.		[ 5]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Gemcitabine	N.A.	Nephrotoxicity	Genotype GG is not associated with increased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AG.		[ 1]
Genetic Polymorphism	rs17215836
Site of GPD	chr15:84895081 (GRCh38.p12)
GPD Type	Indel
Allele(s) in dbSNP	T / TTAT / TTGT
Minor Allele Frequency	T=0.7390/1462 (Global)
Genotype TGT/TGT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Gemcitabine	N.A.	Nephrotoxicity	Genotype TGT/TGT is not associated with increased response to gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes TGT/del + del/del.		[ 1]
Genetic Polymorphism	rs11853372
Site of GPD	chr15:84913115 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>A / T>C / T>G
Minor Allele Frequency	T=0.2490/492 (Global)
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Nephrotoxicity	Genotype TT is not associated with metabolism of gemcitabine as compared to genotypes GG + GT.		[ 6]
Ara-ctp	N.A.	Cardiotoxicity	Genotype TT is associated with decreased concentrations of ara-CTP in children with Leukemia, Myeloid, Acute as compared to genotypes GG + GT.		[ 7]
Genetic Polymorphism	rs8187758
Site of GPD	chr15:84905644 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>A
Minor Allele Frequency	C=0.7040/1393 (Global)
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Nephrotoxicity	Genotype CC is not associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AA + AC.		[ 8]
Gemcitabine	N.A.	Nephrotoxicity	Genotype CC is not associated with increased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AC.		[ 1]
Allele A	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Stavudine	N.A.	Peripheral Nervous System Diseases	Allele A is not associated with risk of Peripheral Nervous System Diseases due to stavudine in people with HIV Infections as compared to allele C.		[ 9]
Genetic Polymorphism	rs2242047
Site of GPD	chr15:84935465 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>T
Minor Allele Frequency	C=0.8840/1749 (Global)
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Nephrotoxicity	Genotype CC is associated with increased response to gemcitabine in people with Colorectal Neoplasms as compared to genotype TT.		[ 10]
Gemcitabine	N.A.	Nephrotoxicity	Genotype CC is not associated with increased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes CT + TT.		[ 1]
Genetic Polymorphism	rs2242048
Site of GPD	chr15:84935179 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	A>G / A>T
Minor Allele Frequency	A=0.0690/136 (Global)
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Nephrotoxicity	Genotype GG is not associated with increased risk of hematologic toxicity when treated with gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AG.		[ 1]
Gemcitabine	N.A.	Cardiotoxicity	Genotype GG is not associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AA + AG.		[ 8]
Genetic Polymorphism	rs3825876
Site of GPD	chr15:84892637 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Minor Allele Frequency	G=0.7480/1480 (Global)
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Genotype AA is associated with increased risk of Neutropenia due to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AG + GG.		[ 11]
Gemcitabine	N.A.	Pancreatic Neoplasms	Genotype AA is associated with increased risk of Neutropenia due to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AG + GG.		[ 11]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Patients with pancreatic cancer and the AG genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the AA genotype. Note that this variant is in high LD with rs12148896 (see clinical annotation 1450373755). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Gemcitabine	N.A.	Pancreatic Neoplasms	Patients with pancreatic cancer and the AG genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the AA genotype. Note that this variant is in high LD with rs12148896 (see clinical annotation 1450373755). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Patients with pancreatic cancer and the GG genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the AA genotype. Note that this variant is in high LD with rs12148896 (see clinical annotation 1450373755). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Gemcitabine	N.A.	Pancreatic Neoplasms	Patients with pancreatic cancer and the GG genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the AA genotype. Note that this variant is in high LD with rs12148896 (see clinical annotation 1450373755). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Genetic Polymorphism	rs12148896
Site of GPD	chr15:84891963 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Minor Allele Frequency	G=0.4300/850 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Allele A is associated with decreased risk of Neutropenia due to gemcitabine in people with Pancreatic Neoplasms as compared to allele G.		[ 11]
Gemcitabine	N.A.	Pancreatic Neoplasms	Allele A is associated with decreased risk of Neutropenia due to gemcitabine in people with Pancreatic Neoplasms as compared to allele G.		[ 11]
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Patients with pancreatic cancer and the AA genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the GG genotype. Note that this variant is in high LD with rs3825876 (see clinical annotation 1450373761). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Gemcitabine	N.A.	Pancreatic Neoplasms	Patients with pancreatic cancer and the AA genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the GG genotype. Note that this variant is in high LD with rs3825876 (see clinical annotation 1450373761). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Genotype AG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Patients with pancreatic cancer and the AG genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the GG genotype. Note that this variant is in high LD with rs3825876 (see clinical annotation 1450373761). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Gemcitabine	N.A.	Pancreatic Neoplasms	Patients with pancreatic cancer and the AG genotype may be at a decreased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the GG genotype. Note that this variant is in high LD with rs3825876 (see clinical annotation 1450373761). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Gemcitabine	N.A.	Neutropenia	Patients with pancreatic cancer and the GG genotype may be at an increased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the AA or AG genotypes. Note that this variant is in high LD with rs3825876 (see clinical annotation 1450373761). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
Gemcitabine	N.A.	Pancreatic Neoplasms	Patients with pancreatic cancer and the GG genotype may be at an increased risk of developing neutropenia as a result of gemcitabine treatment as compared to patients with the AA or AG genotypes. Note that this variant is in high LD with rs3825876 (see clinical annotation 1450373761). Other genetic or clinical factors may also affect a patient's risk of developing neutropenia as a result of gemcitabine treatment.		[ 11]
References
1	Distribution of gemcitabine pathway genotypes in ethnic Asians and their association with outcome in non-small cell lung cancer patients. Lung Cancer. 2009 Jan;63(1):121-7.
2	Gene polymorphisms, pharmacokinetics, and hematological toxicity in advanced non-small-cell lung cancer patients receiving cisplatin/gemcitabine. Cancer Chemother Pharmacol. 2012 Jan;69(1):25-33.
3	Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr Blood Cancer. 2013 Aug;60(8):1375-81.
4	Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J Clin Oncol. 2012 May 1;30(13):1422-8.
5	Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer. Breast Cancer Res Treat. 2013 May;139(1):135-43.
6	SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours. Br J Cancer. 2014 Jan 21;110(2):304-12.
7	Comprehensive Ara-C SNP score predicts leukemic cell intracellular ara-CTP levels in pediatric acute myeloid leukemia patients. Pharmacogenomics. 2018 Sep 01;19(14):1101-1110.
8	Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer. Cancer. 2010 Nov 15;116(22):5325-35.
9	Pharmacogenetic variation influences sensory neuropathy occurrence in Southern Africans treated with stavudine-containing antiretroviral therapy. PLoS One. 2018;13(10):e0204111.
10	Effect of genetic polymorphisms on therapeutic response and clinical outcomes in pancreatic cancer patients treated with gemcitabine. Pharmacogenomics. 2012 Jul;13(9):1023-35.
11	An initial genetic analysis of gemcitabine-induced high-grade neutropenia in pancreatic cancer patients in CALGB 80303 (Alliance). Pharmacogenet Genomics. 2019 Aug;29(6):123-131.

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