Risk assessment of cancer of the female reproductive system
Aim: To create an information resource concerning multifactorial oncological diseases of the female reproductive system. Materials and Methods: A comprehensive search of the literature in the PubMed and Ukrainian scientific sources published from 1995 to 2014 and the results of researches performed...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2014
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| Цитувати: | Risk assessment of cancer of the female reproductive system / N.M. Glushchenko, I.P. Nesina, N.P. Iurchenko, L.A. Proskurnya, L.G. Buchynska // Experimental Oncology. — 2014. — Т. 36, № 3. — С. 207-211. — Бібліогр.: 46 назв. — англ. |
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irk-123456789-1453682019-01-22T01:23:19Z Risk assessment of cancer of the female reproductive system Glushchenko, N.M. Nesina, I.P. Lurchenko, N.P. Proskurnya, L.A. Buchynska, L.G. Original contributions Aim: To create an information resource concerning multifactorial oncological diseases of the female reproductive system. Materials and Methods: A comprehensive search of the literature in the PubMed and Ukrainian scientific sources published from 1995 to 2014 and the results of researches performed in R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine. Development environment of information resource “Multifactorial oncological disease” was Borland Delphi. Results: The information content of web page concerning cancers of the female reproductive system was posted in the information resource “Multifactorial oncological disease”. The assessment algorithm of genetic contribution to cancers of the female reproductive system and recurrent risk of cancer development in families have been described. These algorithms can be used in assessment of contribution of genetic and environmental factors in the development of malignant tumors. Key Words: cancers of the female reproductive system, information resource, genetic contribution, recurrent risk. 2014 Article Risk assessment of cancer of the female reproductive system / N.M. Glushchenko, I.P. Nesina, N.P. Iurchenko, L.A. Proskurnya, L.G. Buchynska // Experimental Oncology. — 2014. — Т. 36, № 3. — С. 207-211. — Бібліогр.: 46 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/145368 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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English |
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Original contributions Original contributions |
| spellingShingle |
Original contributions Original contributions Glushchenko, N.M. Nesina, I.P. Lurchenko, N.P. Proskurnya, L.A. Buchynska, L.G. Risk assessment of cancer of the female reproductive system Experimental Oncology |
| description |
Aim: To create an information resource concerning multifactorial oncological diseases of the female reproductive system. Materials and Methods: A comprehensive search of the literature in the PubMed and Ukrainian scientific sources published from 1995 to 2014 and the results of researches performed in R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine. Development environment of information resource “Multifactorial oncological disease” was Borland Delphi. Results: The information content of web page concerning cancers of the female reproductive system was posted in the information resource “Multifactorial oncological disease”. The assessment algorithm of genetic contribution to cancers of the female reproductive system and recurrent risk of cancer development in families have been described. These algorithms can be used in assessment of contribution of genetic and environmental factors in the development of malignant tumors. Key Words: cancers of the female reproductive system, information resource, genetic contribution, recurrent risk. |
| format |
Article |
| author |
Glushchenko, N.M. Nesina, I.P. Lurchenko, N.P. Proskurnya, L.A. Buchynska, L.G. |
| author_facet |
Glushchenko, N.M. Nesina, I.P. Lurchenko, N.P. Proskurnya, L.A. Buchynska, L.G. |
| author_sort |
Glushchenko, N.M. |
| title |
Risk assessment of cancer of the female reproductive system |
| title_short |
Risk assessment of cancer of the female reproductive system |
| title_full |
Risk assessment of cancer of the female reproductive system |
| title_fullStr |
Risk assessment of cancer of the female reproductive system |
| title_full_unstemmed |
Risk assessment of cancer of the female reproductive system |
| title_sort |
risk assessment of cancer of the female reproductive system |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2014 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/145368 |
| citation_txt |
Risk assessment of cancer of the female reproductive system / N.M. Glushchenko, I.P. Nesina, N.P. Iurchenko, L.A. Proskurnya, L.G. Buchynska // Experimental Oncology. — 2014. — Т. 36, № 3. — С. 207-211. — Бібліогр.: 46 назв. — англ. |
| series |
Experimental Oncology |
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2025-07-10T21:30:40Z |
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| fulltext |
Experimental Oncology 36, 207–211, 2014 (September) 207
RISK ASSESSMENT OF CANCER
OF THE FEMALE REPRODUCTIVE SYSTEM
N.M. Glushchenko1, *, I.P. Nesina1, N.P. Iurchenko1, L.A. Proskurnya2, L.G. Buchynska1
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine,
Kyiv 03022, Ukraine
2National Cancer Institute, Kyiv 03022, Ukraine
Aim: To create an information resource concerning multifactorial oncological diseases of the female reproductive system. Materi-
als and Methods: A comprehensive search of the literature in the PubMed and Ukrainian scientific sources published from
1995 to 2014 and the results of researches performed in R.E. Kavetsky Institute of Experimental Pathology, Oncology and Ra-
diobiology, National Academy of Sciences of Ukraine. Development environment of information resource “Multifactorial onco-
logical disease” was Borland Delphi. Results: The information content of web page concerning cancers of the female reproductive
system was posted in the information resource “Multifactorial oncological disease”. The assessment algorithm of genetic contribu-
tion to cancers of the female reproductive system and recurrent risk of cancer development in families have been described. These
algorithms can be used in assessment of contribution of genetic and environmental factors in the development of malignant tumors.
Key Words: cancers of the female reproductive system, information resource, genetic contribution, recurrent risk.
Despite progress in anticancer campaign in Ukraine,
this problem is still relevant for public health. According
to the data of epidemiological studies of National Can-
cer Institute of Ukraine, overall incidence of malignant
neoplasms (MN) in Ukraine has increased in 2011 com-
pared with 2010 on 2.7% among female population and
on 1.6% among men. When characte rizing structure
of MN morbidity in 2011, we can note that MN of breast,
corpus uteri, uterine cervix, colorectal cancer and
non-melanoma skin MN take rank places among
women — 58.8% and the most widespread MN in men
are prostate gland cancer, gastric, colorectal, lung
cancer, non-melanoma skin MN — 57.8% [1] .
To date, it is beyond the question that cancer prob-
lem can be solved only on conditions of development
of measures of cancer disease prophylaxis, increase
of level of timely diagnostics of MN and carrying out
of adequate therapy. One more condition which has
essential significance for improvement of treatment
results is providing of patient care institutions with
modern equipment and instrumentation and increase
of level of vocational training of oncologists.
Subsidiary, and in series of cases, crucial sig-
nificance for timely diagnostics and determination
of treatment tactics have modern knowledge which
can be obtained in systematized, formalized and
structured forms.
However, dynamic development of computer
information technologies in medical and biological
spheres can both accelerate and complicate obta ining
and interpretation of required information on given
problem in connection with its permanent updating,
representation in various formats and by different
stage of detailing.
For this reason, important element of treatment-
and-diagnostic process is creation of information
resource as theoretical basis with system of hyperlinks
on Internet resources for effective access to informa-
tion and its use as basis for development of prophy-
laxis system and algorithms of diagnostics of cancer
diseases which would include methods of assessment
of hereditary and recurrent risk of MN of different
genesis.
Aim of the research was to create information
resource on multifactorial cancer diseases of female
reproductive system which occurrence has polygenic
nature.
METHODS
Systemic analysis of the problem, generalization
of information, structural and functional study of sub-
ject for the application of knowledge in the context
of multifactorial cancer diseases have been used.
Development environment of information resource
was Borland Delphi. For the functioning of system,
operating platform Windows and dynamic libraries
of Delphi resources have been used.
RESULTS AND DISCUSSION
Work on creation of information resource “Multifac-
torial cancer diseases” has been divided in the stages
by degree of topicality and sequence of their perfor-
mance which included analysis of information (gene-
ralization and systematization of theoretical knowledge
of foreign and national scientific literature as well
as results of own studies of stuff of the R.E. Kavetsky
Institute of Experimental Pathology, Oncology and
Radiobiology of NAS of Ukraine, choice of conception
of information presentation), development of struc-
ture, programming and entry of the information.
Information on cancer diseases of female repro-
ductive system, namely risk factors, genetic features
Submitted: June 04, 2014.
*Correspondence: E-mail: laboncogen@yandex.ua
Abbreviations used: BC — breast cancer; CFRS — cancers
of the female reproductive system; CUC — cancer of the uterine
cervix; EC — endometrial cancer; HPV — human papilloma virus;
MN — malignant neoplasms; OC — ovarian cancer.
Exp Oncol 2014
36, 3, 207–211
208 Experimental Oncology 36, 207–211, 2014 (September)
of MN, prognostic markers and prophylactic measures
concerning occurrence of cancer diseases has been
analyzed.
On the basis of analysis, a structure has been
developed which included the following parts for
each localization: classification of malignant tumors
by TNM (2009), FIGO (2009) and WHO (2014) and their
phenotype parameters, algorithm of diagnostics and
prognostic markers.
According to the structured information concern-
ing endo- and exogenous factors of predisposition
to MN, it has been determined that most of cancers
of the female reproductive system (CFRS) are multi-
factorial diseases. It means that occurrence of such
cancer diseases is connected both with genetic factors
and with impact of various bad environmental factors
which cause the disorders of systems of regulation
of differentiation and proliferation of cells. At that,
multifactorial inheritance and part of hereditary factor
varies for individuals of different sex by age, for tumors
of different genesis and geographic regions [2–5].
When analyzing inheritance of breast cancer (BC),
ovarian cancer (OC) and cancer of the uterine cervix
(CUC) within the framework of multifactorial model,
genetic determinant in development of these diseases
constitutes 55.7 ± 2.4%; 66.8 ± 6.3% and 2.9 ± 2.6%,
correspondingly. These data show that, on the one
hand, there is different impact of genetic and envi-
ronmental factors on development of the disease,
and, on the other hand, they are heterogeneous [3–5].
Some other researchers have determined certain
relation between malignant process and individual
predisposition to occurrence of tumor. For instance,
we shall focus on some important results of study,
namely occurrence of 85–90% of BC cases is con-
nected with epigenetic changes in BRCA1 gene [6, 7],
in 15–43% of cases — with amplification of HER2/neu
(ErbB-2) gene [8], and in 20% of cases — with spon-
taneous mutations of ТР53 gene and in 12.0% — with
mutations of MMR family genes [9]. It should be men-
tioned that 5–10% of cases of OC develops on the
background of germinal mutations of series of genes-
suppressors (BRCA1/BRCA2, TP53, CHEK2, PTCH,
VHL, NBS1), genes of FANC and MMR family which are
responsible for reparation of unpaired bases of DNA
within the limits of series of family cancer syndromes.
It has been showed that risk of OC in women with Lynch
syndrome II constitutes 9–12% [10–13]. At the same
time, decrease of expression of BRCA1 gene (in result
of epigenetic changes or alternative splicing) has been
noted in 65–82% of sporadic cases of OC [14, 15]. Be-
sides mentioned above, in 50–66% of malignant ova-
rian neoplasms, inactivation (mutations or epigenetic
changes) of gene-suppressor TP53 [16–18] is being
determined, in 28.0–40.0% — decrease of expression
of PTEN gene [19], amplification of genes Her2/neu
(ЕrbB-2) — in 16–32%, EGFR (с-erbB-1) — in 9–17%
of cases and in 15% of cases — mutation changes
of KRAS gene [20, 21].
Our studies have determined significant decrease
of expression of receptors of estrogens and proges-
terone in highly proliferative and low differentiated
serous OC [22].
Molecular aspects of development of endometrial
malignant tumors are broadly covered in literature. For
instance, occurrence of endometrioid adenocarci-
noma in 83% of cases is associated with inactivation
of PTEN gene (mutations or deletions), mutations
of genes РІK3СА (26–36%), KRAS (10–30%), —
β-catenin/CTNNB1 (14–44%) and TP53 (10–20%),
inactivation of р16INK4a (10%), amplification of Her2/
neu (10–30%) and loss of E-cadherin (10–20%
of cases) [23].
In contrast to previously mentioned, in serous ma-
lignant endometrial tumors, genetic changes in listed
above genes are to be found with other frequency.
Mostly in such tumors are detected mutations in gene-
suppressor TP53 (90%), loss of E-cadherin is deter-
mined in 60–90% of cases, inactivation of р16INK4a
in 40–45% of tumors, amplification of Her2/neu
in 18–80% of observations. Along with it, changes
in functioning of PTEN gene is being observed only
in 11% of cases, mutations in РІK3СА — 5%, KRAS
and CTNNB1 are detected in 5–10% of tumors [23].
It has been showed that increased risk of endometrial
cancer (EC) and early debut of colorectal cancer are
associated with family history of women both without
mutation of genes of MMR family and with mutations
in these genes within the limits of Lynch syndrome,
have general hereditary and environmental factors [24,
25]. Despite contribution of genetic component
to occurrence of CUC is quite insignificant (2.9%), but
in tumor cells of uterine cervix spontaneous mutations,
deletions or epigenetic changes of genes-suppressors
ST3, FHIT, proto-oncogenes EGFR, FGFR3 and c-MYC
and oncogene c-FOS are registered [5, 26–30].
Along with this, it has been determined to date that
le ading role in development of CUC belongs to human
papilloma virus (HPV) [31–33], oncogenes EGFR,
FGFR3 та c-MYC and oncogene c-FOS [5, 26–30].
Some researchers state that infection agents,
as HPVs, are risk factors of occurrence not only of CUC,
but also have certain pathogenic role in deve lopment
of EC, OC and BC [34–39]. It can be confirmed not only
by results of our previous studies which have showed
that in the condition of infection by virus, tumor cells
of ovary are characterized by low expression of pro-
teins — tumor suppressors р53 and pRb [40–42] that
is typical for HPV-associated neoplasms.
It is known that “trigger” of pathological process
can be both genetic and environmental factors as-
sociated with high risk of MN. Vector of development
of MN is determined depending on individual genetic
constitution of organism. For instance, along with im-
pact of biological factors influencing the occurrence
of cancer diseases, potential ecological risk factors
which are connected with environment in concrete
geographical region and physical and chemical agents
cannot be excluded [43–46].
Experimental Oncology 36, 207–211, 2014 (September) 209
At the same time, question concerning assessment
of MN risk still remains open, namely question con cerning
contribution of hereditary and environmental factors
to development of MN, exactly CFRS, criteria of individual
prognosis of this pathology are also not determined.
In part “Prognostic markers”, rates of unfavorable
clinical course of disease, measures of prophylaxis
according to the each localization of CFRS are given.
Part “Algorithm of diagnostics” included informa-
tion according with subsections: clinical criteria; labo-
ratory indexes; risk factors. The latter includes develo-
ped by us algorithm of assessment of risk of disease,
to be exact cancer, which is located in information field
of the resource “Multifactorial cancer diseases”. As-
sessments of genetic predisposition to cancer patho-
logy (Fig. 1) and recurrent risk of disease in progenies
(Fig. 2) are carried out by clinical and genealogical data
obtained at individual inquiry of persons or patients
with histologically verified diagnosis.
Determination of population frequency of disease
Determination of number of healthy/affected individuals
in pair “parents-children” by clinical and genealogical data
Calculation of interclass correlation coefficients of frequency of disease
between close proband’s relatives
Determination of hereditary model: monogenic/multifactorial
Determination of number of correlation pairs
between proband’s relatives relatives
Determination of correlation coefficients for component division
of dispersion
Fig. 1. Algorithm of assessment of contribution of genetic and
environmental components to predisposition to disease
Algorithm 1 includes:
• determination of population frequency in calcu-
lated time period by data on population size and
population morbidity in corresponding geographi-
cal region;
• determination of frequency of occurrence of di-
sease and number of affected relatives by principles
of analysis of individual’s pedigree (proband’s);
• determination of relations between proband’s rela-
tives (genetic-correlation analysis) for assessment
of genetic predisposition to disease;
• calculation of correlation coefficients between
relatives before manifestation of disease within
the limits of monogenic model (alternative distribu-
tion of predisposition to disease) and multifactorial
model (quasi-continuous distribution);
• carrying out of genetic analysis of multifactorial
signs (component analysis);
• assessment of correlative contribution of genetic
and environmental components to occurrence
of disease taking into account coefficient of affinity
using procedure of component division of pheno-
type dispersion for determination of role of heredi-
tary factor by proband’s pedigrees in determination
of occurrence of disease.
Determination of population frequency of disease
Selection by clinical and genealogical data of group of patients
depending on type of marriage of proband’s parents (mother-father)
and association of tumors proband-sibs
♀ Normal × Normal ♂ ♀ Normal × Affected ♂
♀ Affected × Normal ♂ ♀ Affected × Affected ♂
Determination of data for calculation of segregation frequencies: number
of probands; total number of children; number of affected children;
number of families
Calculation of segregation frequencies by type of registration of families
Comparison of empirical and theoretical segregation frequencies
Carrying out of test of monogenic autosomal inheritance:
dominant/recessive model
Calculation of recurrent risk of occurrence of disease in descendants
Fig. 2. Algorithm of assessment of recurrent risk of disease
in progenies
Algorithm 2 includes:
• determination of population frequency in calcu-
lated period of time by data on population size and
population morbidity in corresponding geographi-
cal region;
• formation of groups according to clinical and ge-
nealogical information depending on type of mar-
riage of proband’s parents (normal or affected);
• determination of quantitative rates of normal-
affected persons in family;
• carrying out of segregation analysis: distribution of dis-
ease in series of generations according to monogenic
(autosomal-dominant and autosomal-recessive type
of inheritance) and polygenic (multifactorial) model
with differentiating approach considering family history
of cancer according to gene alogic data;
• comparison between empirical segregation fre-
quencies and theoretically expected frequencies
for prognosticated type of inheritance;
• calculation of recurrent risk of disease in progenies
based on segregation frequencies.
Practical use of algorithms 1 and 2 at clinical and
genealogical examination of 142 patients with EC living
in Kyiv region allowed obtaining the following results.
1. It was determined that the population frequency
of EC in women of Kyiv region equaled to 0.26%.
2. Coefficient of genetic correlation between first
degree relatives of proband with EC was 0.53 that
corresponds to the quasi-continuous distribution
of predisposition to CFRS.
3. Contribution of genetic factors in the develop-
ment of CFRS constituted 53.2 ± 5.6%, environmental
factors — 46.8 ± 5.6%.
4. Quantitative indexes of association EC — CFRS
were determined in sisters of proband consi dering
the type of parents’ marriage: both parents are
healthy — N×N (Normal-Normal) and one or both
parents of proband are cancer-affected — N×A
210 Experimental Oncology 36, 207–211, 2014 (September)
(Normal-Affected) and A×A (Affected-Affected)
and segregation frequency of cancer development
in families was calculated. If proband has healthy
parents — segregation frequency constitutes 1.89 ±
0.009, cancer affected parents — 4.38 ± 0.034.
5. The model of inheritance on the basis of test-
ing of monogenic autosomal inheritance by Stu-
dent’s criterion was determined. The obtained in-
dexes exce eded critical values at level of significance
t(5%) = 1.96, indicating that dominant and recessive
models cannot be fully accepted.
6. The probability of CFRS development was calculat-
ed for probands’ descendants depending on the health
of parents: for the first child of healthy parents, cancer
risk constitutes 0.3%, and for the se cond child — 1.6%.
In cancer affected parents, pro bability of cancer for the
first child equals 13.5, for the second — 19.3%.
Thus, information resource “Multifactorial cancer
diseases” provides effective access to the information
concerning cancer diseases of polygenic nature with
the aim to use them in scientific and practical activity
in the field of cancer genetics.
The main technical parameters of information
resource are that it is directed to the work both
in auto nomous (network) and local version without
limitation of number of users. In program, the mecha-
nism of direct editing of data in web-fields without
use of additional editors of HTML-documents has
been implemented. Organization of simple interface
is adapted for users who are not specialists in the
domain of information technologies.
Represented algorithm of assessment of contribu-
tion of genetic and environmental components to pre-
disposition to occurrence of diseases, including cancer,
as well as recurrent risk of cancer in progenies, can
be used as base for development and realization of pre-
ventive measures in medical and genetic consulting.
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