Gender effects of single nucleotide polymorphisms and miRNAs targeting clock-genes in metastatic colorectal cancer patients (mCRC)

Carlo Garufi, Elisa Giacomini, Angela Torsello, Isabella Sperduti, Elisa Melucci, Marcella Mottolese, Massimo Zeuli, Giuseppe Maria Ettorre, Teresa Ricciardi, Francesco Cognetti, Mauro Magnani, Annamaria Ruzzo

Research output: Contribution to journalArticlepeer-review

Abstract

The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR-132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females). Longer overall survival (OS) was observed in women compared to men, 50 versus 31 months. This difference was associated with rs11133373 C/C genotype (p = 0.01), rs1801260 T/C+C/C genotype (p = 0.06) and rs11133391 T/T genotype (p = 0.06). Moreover women expressing high levels (H) of miR-192 (p = 0.03), miR-206 (p = 0.003), miR-194 (p = 0.02) and miR-219 (p = 0.002) had a longer OS compared to men. In women longer OS was reinforced by the simultaneous presence of two or more H-miR, 58 months versus 15 months (p = 0.0008); in this group of women an OS of 87 months was reached with the additional presence of rs11133391T/T genotype (p = 0.02). In this study we identified a subgroup of female patients who seems to have a better prognosis. Personalized medicine should prospectively take into account both genetic and gender differences.

Original languageEnglish
Article number34006
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Sep 26 2016

ASJC Scopus subject areas

  • General

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