rs11141915 (DAPK1): Gemcitabine Toxicity Risk
Key takeaways
- rs11141915 sits in the DAPK1 gene on chromosome 9q21
- Carriers showed roughly 4 times higher odds of severe white blood cell loss during gemcitabine chemotherapy
- The finding comes from one small study of 174 patients and should be considered preliminary
- Combining 4 risk SNPs raised the odds of severe toxicity as high as 50 times above the lowest-risk group
- No lifestyle factors have been linked to this variant in the available research
Key takeaways
- rs11141915 sits within the DAPK1 (Death-Associated Protein Kinase 1) gene on chromosome 9q21
- Carriers of the risk genotype showed roughly 4 times higher odds of severe white blood cell loss during gemcitabine chemotherapy
- Evidence comes from a single small study of 174 patients and should be considered preliminary
- Combining four genetic risk markers pushed odds of severe toxicity as high as 50 times above the lowest-risk group
- No lifestyle factors have been linked to this variant in the available literature
What the research says A 2012 genome-wide association study (GWAS) genotyping over 610,000 SNPs across 174 cancer patients identified rs11141915, located in DAPK1 on chromosome 9q21, as one of four loci possibly associated with gemcitabine-induced severe leukopenia/neutropenia - a dangerous reduction in white blood cells - with a combined odds ratio of 4.10 (Kiyotani et al., Pharmacogenetics and genomics, 2012). When patients were classified by the total number of risk genotypes across all four identified SNPs, those carrying two risk genotypes showed an odds ratio of 11.97 and those carrying three showed an odds ratio of 50.00 relative to patients with zero or one risk genotype, suggesting a strongly compounding polygenic effect on toxicity risk.
Reported associations
- Gemcitabine-induced leukopenia/neutropenia (Grade ≥3): rs11141915 in DAPK1 was associated with roughly 4-fold higher odds (OR=4.10) of severe white blood cell reduction in cancer patients receiving gemcitabine, identified in a two-phase GWAS of 174 patients (54 cases with grade ≥3 toxicity, 120 controls with no toxicity)
- Combined polygenic toxicity risk (4-SNP score): In patients carrying two of four identified risk genotypes (including rs11141915), OR=11.97; in those carrying three risk genotypes, OR=50.00, relative to the zero-or-one-risk-genotype reference group
Evidence quality All evidence derives from a single two-phase GWAS (Kiyotani et al., Pharmacogenetics and genomics, 2012) with a combined sample of 174 patients - 54 cases and 120 controls - which is markedly small by current GWAS standards, where well-powered studies typically enrol tens of thousands of participants. The authors describe the four loci as "possibly associated," and the reported P-values do not clearly reach the conventional genome-wide significance threshold of P<5×10^-8 based on the values presented. No independent large-scale replication cohort is described in the available source material. The effect size (OR=4.10 for rs11141915 alone) is notable if confirmed, but the preliminary nature of the evidence and the small sample size warrant caution. This finding should not be considered established until replicated.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What does the DAPK1 gene do?
DAPK1 (Death-Associated Protein Kinase 1) is a gene involved in cell death signaling pathways. Its precise role in chemotherapy metabolism or susceptibility to blood cell toxicity is not fully established by the available research.
What is rs11141915?
rs11141915 is a single nucleotide polymorphism - a single-letter variation in DNA - located in the DAPK1 gene on chromosome 9q21. A 2012 study identified it as one of four genetic markers possibly associated with severe side effects during gemcitabine chemotherapy.
Is rs11141915 linked to leukopenia during chemotherapy?
A small 2012 GWAS found that carriers of rs11141915 had roughly 4 times higher odds of developing grade 3 or worse leukopenia (severely low white blood cell count) during gemcitabine treatment. This finding is preliminary and has not been confirmed in large independent cohorts based on the available materials.
What is gemcitabine-induced neutropenia?
Neutropenia is a significant drop in neutrophils, a type of white blood cell essential for fighting infection. When triggered by chemotherapy drugs like gemcitabine, grade 3 or higher neutropenia is a serious adverse effect that may require medical management.
How strong is the evidence for rs11141915?
The evidence is preliminary: it comes from a single study of just 174 patients, which is far below the sample sizes typical for reliable GWAS findings. The loci are described as 'possibly associated,' and no large independent replication is reported in the available source material.