Genotyping panel to assess Hand-Foot Syndrome in T2DM and cancer patients who receive concurrent Platin derivates and Biguanides

Abstract

Objective: Different prevention strategies towards Type II Diabetes Mellitus (T2DM) patients with neuromuscular pain have been assessed in several studies. Recent data reported the correlation between genotype and neuromuscular events in patients, carrying both T2DM and cardiovascular disease, who were administered with statins-based therapy. In light of this, the present study was planned to evaluate whether Pharmacogenomics (PGx) profile can affect neuromuscolar pain in patients carrying T2DM and cancer. For this purpose, we have taken into account a panel of 4 polymorphisms on 4 candidate genes, already known as important markers related to Platin derivate and Biguanides (Pt-B) and peripheral neurotoxicity as “Hand-Foot syndrome” (HFS). Patients and Methods: We genotyped 37 T2DM/cancer patients who underwent anti-diabetic and polypharmacy; 17 of them received concurrent platin derivates and biguanides therapy. Candidate variants were genes encoding drug transporters as ATP-binding cassette subfamily B member (ABCB1), subfamily C member 8 (ABCC8), and drug enzymes as Cytochrome P450 Family (CYP) including CYP2C8*3 and Glutathione S Transpherase P1 (GSTP1). An early evaluation of genotyping costs and benefits was also pointed out. Results: Of 17 patients treated with Pt-B, 12 (65.7%) had adverse peripheral neuropathy events and 5 of them had HFS. Pharmacogenomics analysis showed a lack of any correlation between candidate genes polymorphisms and HFS toxicity. The genotyping results revealed that 14.1% of patients experienced grade >2 neurotoxicity, but none of them developed HFS (Odds Ratio [OR] 12.5, 95% CI 1.32-118.47, p= 0.003). Conclusions: The pharmacogenomic panel considered in the present work may play a decisive role in improving patients’ treatments with both cancer and T2DM. Our experimental results support pharmacogenomics implementation, helping physicians in clinical decisions. Patients will be provided with a better treatment able to minimize neuromuscular pain and increase benefits, in term of both therapy efficacy and economy for national healthcare system.

Keywords

• pharmacogenetics
• genotyping methods
• platin derivates
• biguanides
• neuromuscular pain