THE CHEK2 del5395 IS A FOUNDER MUTATION
WITHOUT DIRECT EFFECTS FOR CANCER RISK
IN THE LATVIAN POPULATION Plonis J*, Kalniete D, Nakazawa-Miklasevica M, Irmejs A, Vjaters E, Gardovskis J, Miklasevics E *Corresponding Author: Juris Plonis, M.D., Institute of Oncology, Riga Stradins University, Dzirciema 16, LV-
1007, Riga, Latvia. Tel: +371-2915-9476. Fax: +371-6706-9904. E-mail: juris.plonis@inbox.lv page: 33
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DISCUSSION
Results obtained in this study support the assumption
that del5395 is a founder mutation in the
Eastern European population, although statistically
significant relationship between the del5395 mutation
and cancers risks could not be established. The frequency
of del5395 in breast cancer patients (0.68%)
was slightly lower than that reported in Poland [4,5],
Czech Republic and Slovakia [2], whereas in ovarian
cancer patients (1.0%) it was similar to that in the
above reports. However, higher frequency of del5395
in the healthy control group significantly lowered the OR of each cancer group in this study. The Chernobyl
liquidators had been exposed to high radiation that
had caused DNA damage and higher cancer development
risk [8].
Radiation is one of the factors activating the
CHEK2 protein. In response to DNA damage, the
CHEK2 protein interacts with several other proteins,
including tumor protein 53 (that is produced from
the TP53 gene). These proteins halt cell division and
determine whether a cell will repair the damage or
self-destruct in a controlled manner (undergo apoptosis).
This process keeps cells with mutated or damaged
DNA from dividing, thus helping to prevent the
development of tumors [1].
It was assumed that the CHEK2 mutation carriers
would be more sensitive to ionizing radiation and thus
have a higher predisposition towards cancer development.
Of the 51 cancer patients with different types
of cancer in the Chernobyl liquidators group in this
study (9.6%), none had the del5395 mutation. The
geriatric control group was designed to estimate the
strength of the del5395 mutation against mortality.
If del5395 correlates with an increase in the rates of
oncological diseases and mortality in the population,
the geriatric group should have lower frequency of
del5395. Nevertheless, we did not observe any statistically
significant difference in the frequency of del5395
between the healthy control group and the geriatric
group (OR = 0.89; 95% CI 0.13-5.28; p = 1). In the
51 Chernobyl liquidators with different localization
of cancers, the del5395 mutation was not identified
(data not shown).
We concluded that the CHEK2 gene del5395 is
a founder mutation in the Latvian population, which,
however, does not have a direct impact on genetic
predisposition toward colorectal, breast, ovarian
and prostate cancer. Moreover, we believe that the
del5395 mutation requires further research to identify
additional genetic and/or environmental factors,
which in combination with the above mutation, increase
the odds of cancer development.
Declaration of Interest. This study was supported
by the State research program “Biomedicine
for Public Health (BIOMEDICINE).” The authors
report no conflicts of interest. The authors alone are
responsible for the content and writing of this article.
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