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

Autor:	Alberto Sobrero, Nicoletta Pella, Mauro Magnani, Maria Teresa Ionta, Pietro Sozzi, Vittorina Zagonel, Luisa Foltran, Francesco Graziano, Roberto Labianca, Silvia Lazzarelli, Monica Ronzoni, Enzo Veltri, Annamaria Ruzzo, Francesca Bergamo, Daniele Turci, Eliana Rulli, Luciano Frontini, Claudio Verusio, Sandro Barni, Claudia Mucciarini, Edoardo Biondi, Vincenzo Ricci, M. Nicolini, Annalisa Bramati, Sara Lonardi, Bruno Massidda, Francesca Galli, F. Galli, Irene Bagaloni
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine medicine.medical_specialty Colorectal cancer lcsh:Medicine Predictive markers Gastroenterology Article 03 medical and health sciences GSTP1 0302 clinical medicine FOLFOX XRCC3 Internal medicine Genotype Medicine lcsh:Science Multidisciplinary biology business.industry lcsh:R medicine.disease Colon cancer 030104 developmental biology Methylenetetrahydrofolate reductase biology.protein lcsh:Q ERCC1 business 030217 neurology & neurosurgery Pharmacogenetics medicine.drug
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-47627-1
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea02efe822c3d2a15edac37f32eb0dd5 http://link.springer.com/article/10.1038/s41598-019-47627-1 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.