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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years in Female versus Male with rs11133373 C/C genotype (A), rs1801260 T/C+C/C genotype (B) and rs11133391 T/T genotype (C).
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f2: Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years in Female versus Male with rs11133373 C/C genotype (A), rs1801260 T/C+C/C genotype (B) and rs11133391 T/T genotype (C).

Mentions: When analysed by gender, results showed a better survival rate in women compared to men with rs11133373 C/C, median PFS of 23 months vs 11 months (2 years-PFS 33.3% vs 6.3%, p = 0.006) and median OS of 57 months vs 18 months (3 years-OS 70.1% vs 25.0%, p = 0.01), respectively (Fig. 2A). In women the C/C genotype was also associated with a longer PFS and OS compared to C/G+G/G genotype (23 months vs 16 months and 57 months vs 44 months, respectively) while the opposite effect happened in men (11 months vs 14 months and 18 months vs 32 months, respectively) (supplementary Table S1).


Gender effects of single nucleotide polymorphisms and miRNAs targeting clock-genes in metastatic colorectal cancer patients (mCRC)
Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years in Female versus Male with rs11133373 C/C genotype (A), rs1801260 T/C+C/C genotype (B) and rs11133391 T/T genotype (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036027&req=5

f2: Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years in Female versus Male with rs11133373 C/C genotype (A), rs1801260 T/C+C/C genotype (B) and rs11133391 T/T genotype (C).
Mentions: When analysed by gender, results showed a better survival rate in women compared to men with rs11133373 C/C, median PFS of 23 months vs 11 months (2 years-PFS 33.3% vs 6.3%, p = 0.006) and median OS of 57 months vs 18 months (3 years-OS 70.1% vs 25.0%, p = 0.01), respectively (Fig. 2A). In women the C/C genotype was also associated with a longer PFS and OS compared to C/G+G/G genotype (23 months vs 16 months and 57 months vs 44 months, respectively) while the opposite effect happened in men (11 months vs 14 months and 18 months vs 32 months, respectively) (supplementary Table S1).

View Article: PubMed Central - PubMed

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.

No MeSH data available.