Gender effects of single nucleotide polymorphisms and miRNAs targeting clock-genes in metastatic colorectal cancer patients (mCRC).
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.
Division of Medical Oncology, Spirito Santo Hospital Pescara, Italy.
Carlo
C
Garufi
Dept. of Biomolecular Sciences (DiSB) University of Urbino "Carlo Bo", Urbino, Italy.
Elisa
E
Giacomini
Division of Medical Oncology Azienda Ospedaliera San Giovanni Addolorata Hospital, Rome, Italy.
Angela
A
Torsello
Biostatistic Unit, Regina Elena National Cancer Institute Rome, Italy.
Isabella
I
Sperduti
Pathology Department Regina Elena National Cancer Institute Rome, Italy.
Elisa
E
Melucci
Pathology Department Regina Elena National Cancer Institute Rome, Italy.
Marcella
M
Mottolese
Division of Medical Oncology Regina Elena National Cancer Institute Rome, Italy.
Massimo
M
Zeuli
General Surgery and Transplantation Unit San Camillo Hospital Rome, Italy.
Giuseppe Maria
GM
Ettorre
Dept. of Biomolecular Sciences (DiSB) University of Urbino "Carlo Bo", Urbino, Italy.
Teresa
T
Ricciardi
Division of Medical Oncology Regina Elena National Cancer Institute Rome, Italy.
Francesco
F
Cognetti
Dept. of Biomolecular Sciences (DiSB) University of Urbino "Carlo Bo", Urbino, Italy.
Mauro
M
Magnani
Dept. of Biomolecular Sciences (DiSB) University of Urbino "Carlo Bo", Urbino, Italy.
Annamaria
A
Ruzzo
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