Disruptions in the circadian clock genes may affect tumor formation

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A group of Argentinian researchers have conducted a study to assess the relationship between the polymorphism of the human clock gene and the risk of getting blood cancer.

According to the National Sleep Foundation, the human body consists of circadian clock genes, or simply known as an internal body clock, which regulates the way the body works each day. The word ai???circadianai??? originates from the Latin words meaning ai???about a dayai???.

The main function of the circadian system is to keep us in sync with the 24-hour-day cycle. Any disruption of the circadian biological clock may trigger a huge range of health problems such as obesity, diabetes, cardiovascular disease, cancer and even early mortality, according to the Division of Sleep Medicine at Harvard Medical School.

The Argentinian researchers, led by Dr. MarAi??a BelAi??n Cerliani from the Laboratory of Cytogenetics and Mutagenesis, La Plata, Argentina, carried out a study to assess the association between PER3 polymorphism and onco-hematological diseases, and analyze whether this variant has an impact on patientai??i??s functionality.

PER3 is a protein coding gene that is a part of the mechanism involved in the circadian clock, according to the human gene database GeneCards. It plays a role in modulating sleep homeostasis in humans.

More relevant to this research is the fact that PER3 and its length polymorphism may have a role in the formation of tumors since clock genes are the main regulators of cell cycle and DNA repair pathways, according to the Argentinian research team.

ai???We conducted a case-control study in 125 patients with onco-hematological diseases and 310 controls. PER3 allelic variants were detected by PCR. A questionnaire was used to obtain sociodemographic data and information about patientai??i??s habits and functionality,ai??? stated Dr. Cerliani and her team.

The questionnaire allowed them to obtain information about the patients, such as changes in weight, changes in appetite, changes in humor, presence of physical/mental fatigue and difficulty sleeping. Any allelic variations ai??i?? i.e., differences in DNA sequencing ai??i?? in PER3 gene was then detected using polymerase chain reaction (PCR) using the suitable primers.

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Dr. MarAi??a BelAi??n Cerliani

Among interesting findings of this study is that women showed lower risk of disease compared to men and higher levels of education were significantly associated with an increased risk.

ai???Behavior variables such as fatigue, difficulty sleeping, waking up several times at night, or changes in appetite or weight did not associate with hematological cancer. This is probably because the study was hospital-based and more than 75% of the control patients were taking medication at the time of the interview. However, ai???feeling positive or negative changes in humorai??? was significantly associated with onco-hematological diseases,ai??? explained the researchers.

Based on the study conducted, the variable number tandem repeat (VNTR) polymorphism (in which repeated copies of DNA sequence lie next to one another on a chromosome) of PER3 increased the risk of onco-hematological diseases by 39%, although the result was not significant.

When the researchers analyzed the distribution of PER3 genotypes among controls and cases, they found that cancer patients with the 4/5 genotype (or heterozygous, i.e., referring to a pair of genes that are different from each other) or 5/5 genotype (homozygous, i.e., a pair of genes that are the same) had greater fatigue on awakening.

ai???Our results suggest that cancer patients with 4/5 or 5/5 genotype may suffer fatigue more intensely, since they combine circadian disruption from the pathology itself with an increased susceptibility to sleep deprivation due to PER3 genotype,ai???explained the study.

The data points obtained show that the VNTR of PER3 may be a significant marker for individual differences in sleep. It may also be a marker for susceptibility to sleep disruption and disruption of the circadian phase.

ai???All these data show that the VNTR of PER3 may have a role in the risk of leukemia, and it may be a significant marker for individual differences in sleep, vulnerability to sleep disruption and circadian phase misalignment. The investigations aimed at elucidating the molecular connection between circadian genes and carcinogenesis will be helpful in identifying individuals at a higher risk or more susceptible to circadian disruption. It is worth to note that circadian disruption may decrease the physiological defenses against the tumor,ai??? concluded Dr. Cerliani and her team.

The team has published their results in the December 2015 issue of the journal of Advances in Modern Oncology Research.

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