Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy

Annamaria Ruzzo, Francesco Graziano, Francesca Galli, Fabio Galli, Eliana Rulli, Sara Lonardi, Monica Ronzoni, Bruno Massidda, Vittorina Zagonel, Nicoletta Pella, Claudia Mucciarini, Roberto Labianca, Maria Teresa Ionta, Irene Bagaloni, Enzo Veltri, Pietro Sozzi, Sandro Barni, Vincenzo Ricci, Luisa Foltran, Mario NicoliniEdoardo Biondi, Annalisa Bramati, Daniele Turci, Silvia Lazzarelli, Claudio Verusio, Francesca Bergamo, Alberto Sobrero, Luciano Frontini, Mauro Magnani

Research output: Contribution to journalArticle

Abstract

Polymorphisms contribute to inter-individual differences and show a promising predictive role for chemotherapy-related toxicity in colon cancer (CC). TOSCA is a multicentre, randomized, non-inferiority, phase III study conducted in high-risk stage II/stage III CC patients treated with 6 vs 3 months of FOLFOX-4 or XELOX adjuvant chemotherapy. During this post-hoc analysis, 218 women and 294 men were genotyped for 17 polymorphisms: TYMS (rs34743033, rs2853542, rs11280056), MTHFR (rs1801133, rs1801131), ERCC1 (rs11615), XRCC1 (rs25487), XRCC3 (rs861539), XPD (rs1799793, rs13181), GSTP1 (rs1695), GSTT1/GSTM1 (deletion +/−), ABCC1 (rs2074087), and ABCC2 (rs3740066, rs1885301, rs4148386). The aim was to assess the interaction between these polymorphisms and sex, on safety in terms of time to grade ≥3 haematological (TTH), grade ≥3 gastrointestinal (TTG) and grade ≥2 neurological (TTN) toxicity. Interactions were detected on TTH for rs1801133 and rs1799793, on TTG for rs13181 and on TTN for rs11615. Rs1799793 GA genotype (p = 0.006) and A allele (p = 0.009) shortened TTH in men. In women, the rs11615 CC genotype worsened TTN (co-dominant model p = 0.008, recessive model p = 0.003) and rs13181 G allele improved the TTG (p = 0.039). Differences between the two sexes in genotype distribution of rs1885301 (p = 0.020) and rs4148386 (p = 0.005) were found. We highlight that polymorphisms could be sex-specific biomarkers. These results, however, need to be confirmed in additional series.

Original languageEnglish
Article number11527
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Ruzzo, A., Graziano, F., Galli, F., Galli, F., Rulli, E., Lonardi, S., Ronzoni, M., Massidda, B., Zagonel, V., Pella, N., Mucciarini, C., Labianca, R., Ionta, M. T., Bagaloni, I., Veltri, E., Sozzi, P., Barni, S., Ricci, V., Foltran, L., ... Magnani, M. (2019). Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy. Scientific Reports, 9(1), [11527]. https://doi.org/10.1038/s41598-019-47627-1