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

• Published in: Cancer chemotherapy and pharmacology 2021-11, Vol.88 (5), p.813-823
• Main Authors: Duran, Goretti, Cruz, Raquel, Aguín, Santiago, Barros, Francisco, Giráldez, José María, Bernárdez, Beatriz, Zarra, Irene, López-López, Rafael, Carracedo, Ángel, Lamas, María Jesús
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Cancer; Cancer Research; Chemoradiotherapy; Chemotherapy; Deoxyribonucleic acid; DNA; DNA repair; Drug metabolism; ERCC2 gene; Female; Gelatinase A; Gene Frequency; Genes; Genetic diversity; Genetic variance; Genotypes; Haplotypes; Head & neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - therapy; Health risks; Humans; Male; Matrix Metalloproteinase 2 - genetics; Medicine; Medicine & Public Health; Metabolism; Middle Aged; Multidrug Resistance-Associated Protein 2 - genetics; Oncology; Original Article; Patients; Pharmacogenomic Variants; Pharmacology/Toxicology; Platinum; Polymorphism, Single Nucleotide; Radiation therapy; Repair; Risk assessment; Single-nucleotide polymorphism; Subgroups; Survival; Treatment Outcome; Xeroderma Pigmentosum Group D Protein - genetics
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-021-04330-1

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.