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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