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4CPS-069 Influence of genetic variants in the vitamin D hydroxylation pathway as a response factor to platinum-based chemotherapy in non-small cell lung cancer
  1. LE Pineda Lancheros1,
  2. JM Gálvez Navas1,
  3. C Pérez Ramírez2,
  4. MR Cantudo Cuenca3,
  5. A Jiménez Morales3
  1. 1Pharmacogenetics Unit, Pharmacy Service, University Hospital Virgen de las Nieves, Granada, Spain
  2. 2Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain
  3. 3Pharmacy Service, University Hospital Virgen de las Nieves, Granada, Spain


Background and importance Chemotherapy based on platinum compounds is the standard treatment for non-small cell lung cancer (NSCLC) patients with EGFR wild type and is also used as second line in mutated EGFR patients. Vitamin-D may influence chemotherapy response by inhibiting tumour progression, suppressing metastasis, cell proliferation, and angiogenesis, or promoting apoptosis. Therefore, gene polymorphisms in the vitamin D signalling pathway might have an impact on chemotherapy response. Recent studies reported that genetic background plays a key role in the chemotherapy response. However, little is known about the implication of CYP2R1 and CYP27B1 gene polymorphisms, which regulate the activation of circulating vitamin D through hydroxylation, in the response to platinum-based chemotherapy.

Aim and objectives The aim of this study was to evaluate the influence of polymorphisms in the CYP2R1 and CYP27B1 genes on the platinum-based chemotherapy response in patients with NSCLC.

Material and methods A prospective cohort study was conducted. 165 patients diagnosed with NSCLC between 2003 and 2019, followed-up until December 2020. CYP27B1 (rs4646536, rs3782130, rs703842, rs10877012) and CYP2R1 (rs10741657) polymorphisms were analysed by real-time PCR using TaqMan probes. Response (CR: complete response, PR: partial response) and no response (SD: stable disease, PD: progressive disease) were evaluated.

Results Patients’ median age at NSCLC diagnosis was 62 (53–67) years; 73.3% (121/165) men; 69.09% (114/165) stage IIIB-V; 59.39% (98/165) adenocarcinoma; 58.18% (96/165) family history of cancer; 24.24% (40/165) previous lung disease; EGFR status: 52.73% (87/165) wild type, 10.91% (18/165) mutated, 36.36% (18/165) unknown; 22.56% surgery; 31.52% radiotherapy; chemotherapy agents: 18.29% (30/164) gemcitabine; 21.34% (35/164) paclitaxel; 24.39% (40/164); 35.98% (59/164). 65.85% (108/164) response; 34.15% (56/164) no response.

Patients carrying the CYP2R1-rs10741657-G alleles were associated with better response (p=0.017; OR 3.17; 95% CI 1.19 to 8.42; G vs AA). However, for CYP27B1 (rs4646536, rs3782130, rs703842, rs10877012) we did not find a statistically significant association.

Conclusion and relevance Our results suggest that CYP2R1 rs10741567 G-allele influences response in platinum-based chemotherapy in NSCLC patients. Therefore, this polymorphism could be used as a response biomarker in NSCLC patients undergoing treatment with platinum-based chemotherapy.

Conflict of interest No conflict of interest

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