Table 5.
Single nucleotide polymorphisms in CDA and related phenotypes
| rsID | Location/Effect | Phenotype | PMID |
|---|---|---|---|
| rs2072671 | 79A>C (Lys27Gln) | The C allele was not associated with CDA enzymatic activity compared to the A allele in patients with cancer when treated with gemcitabine and cisplatin. There was a toxic death case (severe hematological toxicity including leukopenia) in the single individual with the AC genotype, who also had CDA enzymatic activity less than 75% of the average of the cohort. | 17885621 |
| rs2072671 | 79A>C (Lys27Gln) | The AC and CC genotypes are associated with increased risk of severe neutropenia compared to genotype AA in people with late stage, or metastatic cancer (NSCLC, bladder, cholangiocellular carcinoma etc.). Some patients received gemcitabine monotherapy, others combination therapy with cisplatin. | 22546611 |
| rs2072671 | 79A>C (Lys27Gln) | The C allele is associated with increased frequency of nausea and vomiting compared to the A allele in people with mesothelioma that were treated with a combination of gemcitabine and platinum compounds. | 22134350 |
| rs2072671 | 79A>C (Lys27Gln) | The AA and AC genotypes are associated with increased risk of severe hematologic toxicity compared to genotype CC in people with pancreatic cancer that are treated with gemcitabine, but not in patients treated with fluorouracil. | 21625252 |
| rs2072671 | 79A>C (Lys27Gln) | The AA genotype is associated with a decreased risk of neutropenia compared to the AC and CC genotypes in people with pancreatic cancer when treated with a combination of gemcitabine and radiotherapy, or platinum. | 20665488 |
| rs2072671 | 79A>C (Lys27Gln) | The AA genotype is associated with increased risk of neutropenia or thrombocytopenia, and improved survival, including longer time to progression compared to genotypes AC and CC in people with stage III or IV NSCLC treated with gemcitabine and cisplatin. The A allele is also associated with decreased CDA enzymatic activity (in vitro). | 18347182 |
| rs2072671 | 79A>C (Lys27Gln) | The AA genotype is not associated with increased risk of neutropenia, or response compared to the AC and CC genotypes in people with NSCLC when treated with a combination gemcitabine and carboplatin. | 18538445 |
| rs2072671 | 79A>C (Lys27Gln) | The A allele is not associated with patient survival, or neurotoxicity compared to the C allele in people with metastatic breast cancer treated with a combination of gemcitabine and paclitaxel. | 24361227 |
| rs2072671 | 79A>C (Lys27Gln) | Genotype AA is associated with decreased activity of CDA in whole blood from healthy volunteers as compared to genotypes AC and CC (in vitro). | 23651026 |
| rs2072671 | 79A>C (Lys27Gln) | Genotype CC is associated with increased expression of CDA in PBMCs (in vitro). | 21521023 |
| rs2072671 | 79A>C (Lys27Gln) | The A allele is associated with decreased enzymatic activity compared to the C allele in cytoplasmic extracts from RBCs (in vitro). | 18600531 |
| rs2072671 | 79A>C (Lys27Gln) | The A allele is associated with decreased enzymatic activity compared to the C allele in in cells transfected with DNA from healthy Caucasian and African-American healthy volunteers (in vitro). | 16551864 |
| rs1048977 | 435C>T (Thr145=) | The TT genotype is associated with increased expression of CDA in peripheral mononuclear blood cells from healthy volunteers (in vitro) | 21521023 |
| rs1048977 | 435C>T (Thr145=) | The CC genotype is not associated with enzymatic activity of CDA in whole blood compared to genotypes CT and TT (in vitro). | 23651026 |
| rs1048977 | 435C>T (Thr145=) | The CC genotype is not associated with response compared to genotypes CT and TT in people with pancreatic cancer when treated with a combination of gemcitabine and radiotherapy, or platinum. | 20665488 |
| rs1048977 | 435C>T (Thr145=) | The C allele is not associated with response compared to the T allele in people with metastatic breast cancer treated with a combination of gemcitabine and paclitaxel. | 24361227 |
| rs1048977 | 435C>T (Thr145=) | The CC and CT genotypes are associated with increased elimination clearance of dFdU, and formation of dFdCTP when compared to the TT genotype in people with cancer. | 22838949 |
| rs1048977 | 435C>T (Thr145=) | The CC genotype is associated with increased response, but is not associated with hematological toxicity compared to genotypes CT and TT in people with NSCLC when treated with a combination of gemcitabine and carboplatin. | 18538445 |
| rs60369023 | 208G>A (Ala70Thr) | The AA genotype is associated with severe risk of toxicity compared to genotype GG. This is a case study of a single patient with pancreatic cancer who was treated with a combination of gemcitabine and cisplatin. | 15814642 |
| rs60369023 | 208G>A (Ala70Thr) | The A allele is associated with decreased clearance of gemcitabine, and increased risk of neutropenia compared to the G allele in people with cancer when gemcitabine is combined with platinum or fluorouracil therapy. | 17194903 |
| rs60369023 | 208G>A (Ala70Thr) | The A allele is not associated with increased risk of neurotoxicity compared to the G allele in people with metastatic breast cancer when treated with gemcitabine and paclitaxel. | 24361227 |
| rs60369023 | 208G>A (Ala70Thr) | The A allele is not associated with catalytic activity of recombinant CDA protein towards gemcitabine (in vitro). | 23230131 |
| rs4655226 | 155-3137C>T | Genotype CC is associated with increased clearance of dFdU compared to genotype CT in people with cancer. | 22838949 |
All alleles reported in the table are on the positive strand. Variants marked by an * are the complement of what is reported in the study.
Abbreviations: NSCLC (non-small cell lung cancer), CDA (cytidine deaminase), dFdU (2', 2' difluorodeoxyuracil), dFdCTP (gemcitabine triphosphate), PBMC (peripheral blood mononuclear cells).