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Predictive value of ERCC2, ABCC2 and MMP2 of response and long-term survival in locally advanced head and neck cancer patients treated with chemoradiotherapy

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Abstract

Purpose

Genetic variants in genes involved in the distribution, metabolism, accumulation or repair of lesions are likely to influence the response of drugs used in the treatment of Head and Neck Cancer (HNC). We examine the effect of 36 SNPs on clinical outcomes in patients with locally advanced HNC who were receiving platinum-based chemoradiotherapy (CRT).

Methods

These SNPs were genotyped in 110 patients using the iPLEX Gold assay on the MassARRAY method in blood DNA samples and used Kaplan–Meier and Cox regression analyses to compare genotype groups with the survival.

Results

Two SNPs, rs717620 (ABCC2) and rs12934241 (MMP2) were strongly associated with overall survival (OS) and disease-free survival (DFS). At a median follow-up of 64.4 months, the allele A of rs717620 (ABCC2) had an increased risk of disease progression {hazard ratio [HR] = 1.79, p = 0.0018} and death (HR = 2.0, p = 0.00027). ABCC2 was associated with OS after a Bonferroni adjustment for multiple testing. The MMP2 rs12934241‐T allele was associated with an increased risk of worse OS and DFS (p = 0.0098 and p = 0.0015, respectively). One SNP of ABCB1 and three SNPs located in the ERCC2 gene showed an association with response in the subgroup of HNC patients treated with definitive CRT.

Conclusions

Our findings highlight the potential usefulness of SNPs in different genes involved in drug metabolism and repair DNA to predict the response and survival to CRT. ABCC2 is a potential predictor of OS in patients with HNC.

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Acknowledgements

Genotyping services were provided by Centro Nacional de Genotipado—Instituto de Salud Carlos III (CeGen-ISCIII), Santiago de Compostela, Spain. We want to express our gratitude to all donors who contributed their samples as well as to their general practitioners of Departments of Oncology Radiotherapy and Otolaryngology-Head and Neck Surgery. They thank Dr. Emilia Balboa for her help to select candidate SNPs included in this study.

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Authors and Affiliations

  1. Pharmacy Department, Clinical University Hospital of Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706, Santiago, Spain

    Goretti Duran, José María Giráldez, Beatriz Bernárdez & Irene Zarra

  2. Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Trav. Choupana s/n, 15706, Santiago, Spain

    Goretti Duran, José María Giráldez, Beatriz Bernárdez, Irene Zarra & María Jesús Lamas

  3. Center for Biomedical Research on Rare Diseases (CIBERER), Genomics Medicine Group, CIMUS, University of Santiago de Compostela, Avenida de Barcelona s/n, 15782, Santiago, Spain

    Raquel Cruz

  4. Department of Medical Oncology, Clinical University Hospital of Santiago de Compostela (SERGAS), 15706, Santiago, Spain

    Santiago Aguín & Rafael López-López

  5. Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706, Santiago, Spain

    Santiago Aguín & Rafael López-López

  6. Genomic Medicine Group, CIBERER, Fundación Pública Galega de Medicina Xenómica-SERGAS, Trav. Choupana s/n, 15706, Santiago, Spain

    Francisco Barros

  7. Genomic Medicine Group, CIBERER, Fundación Pública Galega de Medicina Xenómica-SERGAS, Health Research Institute of Santiago (IDIS), University of Santiago de Compostela, Trav. Choupana s/n, 15706, Santiago, Spain

    Ángel Carracedo

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  1. Goretti Duran
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  3. Santiago Aguín
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Correspondence to Goretti Duran, Raquel Cruz or Ángel Carracedo.

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Duran, G., Cruz, R., Aguín, S. et al. Predictive value of ERCC2, ABCC2 and MMP2 of response and long-term survival in locally advanced head and neck cancer patients treated with chemoradiotherapy. Cancer Chemother Pharmacol 88, 813–823 (2021). https://doi.org/10.1007/s00280-021-04330-1

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