Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease
Aim: to analyze the distribution of males and females by the age of colorectal cancer (CRC) onset with and without hereditary predisposition to the disease to identify individuals at risk group. Subjects and methods: the medical records and the genealogical information of 182 patients with CRC wer...
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| Cite this: | Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease / M.R. Lozynska, O.M. Fedota, L.Yu. Lozynska, N.M. Prokopchuk, R.O. Pinyazhko // Онкологія. — 2016. — Т. 18, № 2. — С. 104-109. — Бібліогр.: 25 назв. — англ. |
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Lozynska, M.R. Fedota, O.M. Lozynska, L.Yu. Prokopchuk, N.M. Pinyazhko, R.O. 2019-01-17T14:10:58Z 2019-01-17T14:10:58Z 2016 Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease / M.R. Lozynska, O.M. Fedota, L.Yu. Lozynska, N.M. Prokopchuk, R.O. Pinyazhko // Онкологія. — 2016. — Т. 18, № 2. — С. 104-109. — Бібліогр.: 25 назв. — англ. 1562-1774 https://nasplib.isofts.kiev.ua/handle/123456789/145165 Aim: to analyze the distribution of males and females by the age of colorectal cancer (CRC) onset with and without hereditary predisposition to the disease to identify individuals at risk group. Subjects and methods: the medical records and the genealogical information of 182 patients with CRC were analyzed, including 94 males and 88 females. «Positive» familial anamnesis for CRC was confirmed in 61 probands: 40 patients to met 1–2 of Amsterdam criteria for Lynch syndrome, 9 patients to met 3 Amsterdam criteria, 7 patients had familial adenomatous polyposis, 3 patients had familial CRC-associated inflammatory bowel diseases, 1 patient had MUTYH-associated polyposis, 1 patient had Peutz — Jeghers syndrome. Results: age manifestation of the disease varied in regarding patient’s gender and family history. In probands with «positive» familial anamnesis for CRC the peak age of the disease onset was 5 years lower for both genders, compared to the age of individuals without family history. The average age of CRC onset in probands of both genders with «positive» familial anamnesis for this disease was the statistically significant lower, than in patients without family history. The statistically significant difference for the average age of the CRC manifestation between males and females without family history was revealed. Conclusion: thus, the study of gender and age-CRC is one of the urgent problems of modern medicine. A precise understanding age of inherited CRC manifestation of patients with CRC is important for identifying at-risk individuals, improving cancer surveillance and prevention strategies, and developing better diagnostic and therapeutic approaches. Мета: провести аналіз розподілу хворих різної статі за віком маніфестації колоректального раку (КРР) зі спадковою обтяженістю та без обтяженості цим захворюванням для виявлення осіб груп ризику. Об’єкт і методи: аналіз медичної документації та генеалогічної інформації у 182 хворих наКРР (94 чоловіки і 88 жінок). «Позитивний» сімейний анамнез КРР підтверджено у 61 пробанда: 40 з них відповідали одному–двом Амстердамським критеріям діагностики, 9 — трьом Амстердамським критеріям, 7 — мали сімейний аденоматозний поліпоз, 3 — спадкову обтяженість наКРР, асоційований іззапальними захворюваннями кишечнику, та по одному випадку MUTYH-асоційованого поліпозу і синдрому Пейтца — Єгерса. Результати: вік маніфестації захворювання варіював залежно від статі пацієнтів і спадкової обтяженості. У пробандів із сімейним анамнезом КРР віковий пік маніфестації захворювання був меншим на 5 років для обох статей порівняно з віком осіб без спадкової обтяженості. У пробандів із КРР чоловічої та жіночої статі зі спадковою обтяженістю цим захворюванням встановлено істотно менший середній вік маніфестації хвороби, ніж у хворих чоловіків і жінок без спадкової обтяженості. Між чоловіками і жінками без спадкової обтяженості КРР за середнім віком маніфестації хвороби встановлено статистично істотну різницю. Висновок: встановлення віку маніфестації спадкових варіантів КРР і статевих особливостей пацієнтів із цим захворюванням є важливим для виявлення осіб груп ризику, а також для покращення спостереження за пацієнтами із раком товстої кишки та відпрацювання превентивної стратегії для вдосконалення діагностики і лікувальних підходів. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Онкологія Оригинальные исследования Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease Характеристика розподілу хворих на колоректальний рак за віком і статтю залежно від спадкової обтяженості цим захворюванням Article published earlier |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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| title |
Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease |
| spellingShingle |
Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease Lozynska, M.R. Fedota, O.M. Lozynska, L.Yu. Prokopchuk, N.M. Pinyazhko, R.O. Оригинальные исследования |
| title_short |
Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease |
| title_full |
Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease |
| title_fullStr |
Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease |
| title_full_unstemmed |
Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease |
| title_sort |
distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease |
| author |
Lozynska, M.R. Fedota, O.M. Lozynska, L.Yu. Prokopchuk, N.M. Pinyazhko, R.O. |
| author_facet |
Lozynska, M.R. Fedota, O.M. Lozynska, L.Yu. Prokopchuk, N.M. Pinyazhko, R.O. |
| topic |
Оригинальные исследования |
| topic_facet |
Оригинальные исследования |
| publishDate |
2016 |
| language |
English |
| container_title |
Онкологія |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| title_alt |
Характеристика розподілу хворих на колоректальний рак за віком і статтю залежно від спадкової обтяженості цим захворюванням |
| description |
Aim: to analyze the distribution of males and females by the age of colorectal cancer
(CRC) onset with and without hereditary predisposition to the disease to identify
individuals at risk group. Subjects and methods: the medical records and the genealogical information of 182 patients with CRC were analyzed, including 94 males
and 88 females. «Positive» familial anamnesis for CRC was confirmed in 61 probands: 40 patients to met 1–2 of Amsterdam criteria for Lynch syndrome, 9 patients to met 3 Amsterdam criteria, 7 patients had familial adenomatous polyposis, 3 patients had familial CRC-associated inflammatory bowel diseases, 1 patient had MUTYH-associated polyposis, 1 patient had Peutz — Jeghers syndrome.
Results: age manifestation of the disease varied in regarding patient’s gender and
family history. In probands with «positive» familial anamnesis for CRC the peak
age of the disease onset was 5 years lower for both genders, compared to the age
of individuals without family history. The average age of CRC onset in probands
of both genders with «positive» familial anamnesis for this disease was the statistically significant lower, than in patients without family history. The statistically
significant difference for the average age of the CRC manifestation between males
and females without family history was revealed. Conclusion: thus, the study of
gender and age-CRC is one of the urgent problems of modern medicine. A precise
understanding age of inherited CRC manifestation of patients with CRC is important for identifying at-risk individuals, improving cancer surveillance and prevention strategies, and developing better diagnostic and therapeutic approaches.
Мета: провести аналіз розподілу хворих
різної статі за віком маніфестації колоректального раку (КРР) зі спадковою обтяженістю та без обтяженості цим захворюванням для виявлення осіб
груп ризику. Об’єкт і методи: аналіз медичної документації та генеалогічної інформації у 182 хворих наКРР (94 чоловіки і 88 жінок). «Позитивний»
сімейний анамнез КРР підтверджено у 61 пробанда: 40 з них відповідали одному–двом Амстердамським критеріям діагностики, 9 — трьом Амстердамським критеріям, 7 — мали сімейний аденоматозний поліпоз, 3 — спадкову обтяженість наКРР,
асоційований іззапальними захворюваннями кишечнику, та по одному випадку MUTYH-асоційованого
поліпозу і синдрому Пейтца — Єгерса. Результати: вік маніфестації захворювання варіював залежно від статі пацієнтів і спадкової обтяженості. У пробандів із сімейним анамнезом КРР віковий пік маніфестації захворювання був меншим
на 5 років для обох статей порівняно з віком осіб
без спадкової обтяженості. У пробандів із КРР чоловічої та жіночої статі зі спадковою обтяженістю цим захворюванням встановлено істотно менший середній вік маніфестації хвороби, ніж у хворих
чоловіків і жінок без спадкової обтяженості. Між
чоловіками і жінками без спадкової обтяженості
КРР за середнім віком маніфестації хвороби встановлено статистично істотну різницю. Висновок:
встановлення віку маніфестації спадкових варіантів КРР і статевих особливостей пацієнтів із цим захворюванням є важливим для виявлення осіб груп ризику, а також для покращення спостереження за пацієнтами із раком товстої кишки та відпрацювання превентивної стратегії для вдосконалення діагностики і лікувальних підходів.
|
| issn |
1562-1774 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/145165 |
| citation_txt |
Distribution characteristics of colorectal cancer patients for gender and age depending of hereditary predisposition to the disease / M.R. Lozynska, O.M. Fedota, L.Yu. Lozynska, N.M. Prokopchuk, R.O. Pinyazhko // Онкологія. — 2016. — Т. 18, № 2. — С. 104-109. — Бібліогр.: 25 назв. — англ. |
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ОНКОЛОГИЯ • Т. 18 • № 2 • 2016
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
104
INTRODUCTION
Colorectal cancer (CRC) is the second of the fourth
most common cancer in industrialized countries, leading
to mortality. In Ukraine, the incidence of malignant tu
mors of colon is 28.3 per 100,000 males, rectum and
anus is 27.2 per 100,000 males; the incidence of malig
nant tumors is 19.7 per 100,000 females and is 15.1 per
100,000 females, respectively. Worldwide incidence
of malignant tumors of the colon, rectum and anus is
16.2 per 100,000 males, and is 15.9 per 100,000 males, re
spectively, and is 11.8 per 100,000 females and is 9.2 per
100,000 females, respectively, and is significantly lower
than in Ukraine [1]. In Europe (in Germany and Nor
way), the highest incidence rate of CRC among men is
43–59 per 100,000 individuals and among women is 27–
37 per 100,000 individuals per year and approximate
ly correspond to the number of patients in the USA [2].
Mortality in patients with colon cancer is 41.8% and for
rectal cancer is 32.9%. Almost half of patients dies in
the first year after diagnosis confirmed. The incidence
of CRC increases after 50 years to 160 or more cases per
100,000 people, and at the age over 60 years it increases
to 259 cases [3]. In Ukraine, 15,000–17,000 new ca ses of
CRC are diagnosed annually. The highest mortality rate
was observed in the age group of individuals over 60 years
(56–60%) [4]. In patients with hereditary CRC the mani
festation of the disease is characterized by a younger age,
a high penetrance of the disease, the preva lence of tumors
with low differentiation, appe arance of metastases both
before treatment and after surgery and lower rate of three
years survival [5]. The etiologies of the rema ining 20–
30% of inherited CRCs are not completely understood.
According to the literature data the diseases with highest
risk of CRC includes hereditary polyposis syndromes,
most often familial ade nomatous polypo sis (FAP), Lynch
syndrome and inflammatory bowel dise ase [6]. In pa
tients with FAP the risk of CRC occurrence is approach
to 100%, and in patients with Lynch syndrome the risk
of CRC is less and accounts to 50–70%. Approximate
ly 25% of patients with colorectal phenotypes indistin
guishable from FAP and its attenua ted form — AFAP,
can be associated with biallelic inherited mutations of
BER (base excision repair) gene, MUTYH (human MutY
homolog) in the absence of demonstrable inherited mu
tations of APC gene. The established role of MUTYH is
BER of adenine residues that have been misincorporated
opposite guanine or 8oxoG [7]. In 60–70% of patients
with MUTYHassociated polyposis (MAP) CRC diag
nosed at an average age of 47 years [8]. The risk of CRC
in patients with Lynch syndrome younger than 45 years
increases in 3 times in comparison to the general popu
lation rate [9].
DISTRIBUTION CHARACTERISTICS
OF COLORECTAL CANCER
PATIENTS FOR GENDER AND AGE
DEPENDING OF HEREDITARY
PREDISPOSITION TO THE DISEASE
Aim: to analyze the distribution of males and females by the age of colorectal cancer
(CRC) onset with and without hereditary predisposition to the disease to identify
individuals at risk group. Subjects and methods: the medical records and the gene-
alogical information of 182 patients with CRC were analyzed, including 94 males
and 88 females. «Positive» familial anamnesis for CRC was confirmed in 61 pro-
bands: 40 patients to met 1–2 of Amsterdam criteria for Lynch syndrome, 9 pa-
tients to met 3 Amsterdam criteria, 7 patients had familial adenomatous polypo-
sis, 3 patients had familial CRC-associated inflammatory bowel diseases, 1 pa-
tient had MUTYH-associated polyposis, 1 patient had Peutz — Jeghers syndrome.
Results: age manifestation of the disease varied in regarding patient’s gender and
family history. In probands with «positive» familial anamnesis for CRC the peak
age of the disease onset was 5 years lower for both genders, compared to the age
of individuals without family history. The average age of CRC onset in probands
of both genders with «positive» familial anamnesis for this disease was the statis-
tically significant lower, than in patients without family history. The statistically
significant difference for the average age of the CRC manifestation between males
and females without family history was revealed. Conclusion: thus, the study of
gender and age-CRC is one of the urgent problems of modern medicine. A precise
understanding age of inherited CRC manifestation of patients with CRC is im-
portant for identifying at-risk individuals, improving cancer surveillance and pre-
vention strategies, and developing better diagnostic and therapeutic approaches.
M.R. Lozynska1
O.M. Fedota2
L.Yu. Lozynska3
N.M. Prokopchuk1
R.O. Pinyazhko3
1SI «Institute of Hereditary
Pathology of NAMS of Ukraine»,
Lviv
2V.N. Karazin Kharkiv National
University, Kharkiv
3Danylo Halytsky Lviv National
Medical University, Lviv, Ukraine
Key Words: colorectal cancer,
familial anamnesis, age
manifestation of the disease,
gender.
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
105ОНКОЛОГИЯ • Т. 18 • № 2 • 2016 105
It is known that 10–15% of deaths from the inflam
matory bowel disease — ulcerative colitis and Crohn’s
disease, caused by CRC. Patients with cancer associa
ted with ulcerative colitis at 10–15 years younger com
pared with patients with sporadic CRC, and for terms
of 5year survival the difference between the two groups
were didn’t observed [10].
The aim of this research is to analyze the distribution
of males and females by the age of CRC onset with and
without hereditary predisposition to the disease to iden
tify individuals at risk group.
SUBJECTS AND METHODS
During the 2002–2014 years it was analyzed the medi
cal records and genealogical information in 182 patients
with CRC, including 94 males and 88 females. The diag
nosis was established using clinical, endoscopic, radio
logical and laboratory methods. All diagnoses were mor
phologically confirmed. Patients were residents of the six
regions of Ukraine: Lviv, IvanoFrankivsk, Ternopil, Vo
lyn, Vinnytsia and Zakarpattya. The collection of gene
alogical information in 3–4 generations was carried out
using a single registration of probands according to the
appropriate ethical requirements. The mode of inheri
tance of the diseases was determined using clinical, ge
nealogical, laboratory and literature (OMIM) database.
The age of CRC onset in cases with familial anamnesis
of cancer was evaluated in the probands only and does
not take into account the age manifestation of the dise
ase in their relatives. Selection of patients in the group of
high risk of Lynch syndrome was performed according
to 1–3 Amsterdam diagnostic criteria.
«Positive» familial anamnesis for CRC was confirmed
in 61 patients. Its including cases, when recurrence of
cancer within the family in one or more of first degree
relatives and in subsequent generations, was established.
Of these, 40 patients (15 males and 25 females) to met
1–2 of Amsterdam criteria for Lynch syndrome, 9 pa
tients to met 3 Amsterdam criteria, and thus confirmed
Lynch syndrome (4 males and 5 females). Only 1 patient
of these group had Lynch syndrome I and other patients
have Lynch syndrome II. The selection of the group of
patients with Lynch syndrome I was carried out consi
dering accordance Amsterdam I diagnostic criteria that
includes three basic requirements:
• onset of CRC in at the least 3 individuals span
ning two generations (FAP should be excluded);
• at least one of these individuals is the firstdegree
rela tive of the other two;
• at least one of the individuals must have a diag
nosis prior to age 50 years [11].
Selection of patients in the risk group of Lynch syn
drome II carried out with regarding supplemented, i.e.
Amsterdam II criteria. Requirements include, in fulfilled
to the same 3 diagnostic criteria I, some additions: Lynch
syndrome II should be suspected in probands and their
relatives with CRC/or extracolonic cancers (endometri
al, hepatobiliary system, stomach, small intestine, skin,
genitourinary cancer) [12]. In 1997, the Natio nal Can
cer Institute published a set of recommendations called
the Bethesda guidelines for the identification of individu
als with synchronous or metachronous tumors who
should receive genetic testing for Lynch syndrome rela
ted tumors. Of Bethesda criteria we considered only item
requirements for the presence of synchronous or meta
chronous CRC without the genetic testing for microsa
tellite instability. Proof of Lynch syndrome I and II are
three compliance Amsterdam I and II diagnostic criteria.
Fulfilled with one or two criteria is regarded as a famili
al cancer of different etiology. 8 patients with «positive»
familial anamnesis for CRC did not fulfill the Amster
dam criteria, had multiple adenomatous polyposis and
CRC. Of these 7 patients (2 males, 5 females) were di
agnosed FAP and one male had MAP. One female had
hamartomatous polyposis — Peutz — Jeghers syndrome.
The remaining three patients had familial CRCassoci
ated inflammatory bowel diseases: 2 males had Crohn’s
disease, and 1 male had ulcerative colitis. The diagnosis
of adenomatous polyposis (FAP, MAP) and hamarto
matous polyposis (Peutz — Jeghers syndrome) was con
firmed using clinical, endoscopic diagnostic criteria, ge
nealogical information and molecular genetic analysis re
sults. The molecular genetic analysis of the DNA samples
of leucocytes of peripheral blood was carried out in the
Institute of Human Genetics of the Polish Academy of
Sciences (Poznan) on the basis of scientific cooperation.
Statistical analysis was performed using standard
methods [13]. The distribution of the obtained data and
its compliance with the predicted theoretical distribution
was evaluated using Pearson’s chisquared test (χ2). Veri
fication of statistical hypotheses performed at p ≤ 0.05.
For the statistical analysis of genetic data «GenePop»
used the computer program, available online (http://
wbiomed.curtin.edu.au/genepop).
RESULTS AND DISCUSSION
Patients with CRC were symbolically divided into two
groups regarding patient’s familial history of the dise
ase: without familial anamnesis for the disease were 121
(66.5%) patients (group 1) and with hereditary predispo
sition for the disease were 61 (33.5%) patients (group 2)
(Table 1).
Table 1
The distribution of males and females with CRC for groups without/
with hereditary predisposition to the disease
Patient’s
gender
(number of
patients)
CRC patients without
family history to the
disease (group 1),
absolute number (%)
CRC patients with family
history to the disease
(group 2),
absolute number (%)
Males
(n = 94) 69 (57) 25 (41)
Females
(n = 88) 52 (43) 36 (59)
Total 121 (100) 61 (100)
The I stage of tumor process was identified in 7 (5.8%)
patients, the II stage were in 81 (67.0%) patients, the
III stage were in 23 (19.0%) patients, and the IV stage
were in 10 (8.2%) patients of the total number of patients
without family history of CRC. Among patients with he
reditary predisposition for CRC the I stage of tumor pro
ОНКОЛОГИЯ • Т. 18 • № 2 • 2016
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
106
cess were diagnosed in 3 (4.9%) patients, the II stage were
in 34 (55.7%), the III stage were in 14 (23.0%) and the
IV stage were in 10 (16.4%) patients (Table 2).
Table 2
The distribution of CRC patients depending of the stages of tu-
mors process in the groups of individuals without/with family histo-
ry to the disease
The stages of
CRC
CRC patients without
family history to the
disease (group 1),
absolute number (%)
CRC patients with family
history to the disease
(group 2),
absolute number (%)
I 7 (5.8) 3 (4.9)
II 81 (67.0) 34 (55.7)
III 23 (19.0) 14 (23.0)
IV 10 (8.2) 10 (16.4)
Total 121 (100) 61 (100)
Earlier tumor stages (I + II) were diagnosed in 88
(72.7%) patients of the group 1 and later tumor sta ges
(III + IV) have 33 (27.3%) individuals, compared to
the number patients of the group 2 — 37 (60,6%) and
24 (39.4%) patients, respectively. Thus, in patients with
a family history of CRC were diagnosed more advanced
forms of the disease.
The distribution of males and females by the age of
CRC onset is shown on Fig. 1.
0
5
10
15
20
25%
Years
Males
Females
25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80 and >
Fig. 1. The distribution of males and females by age manifes
tation for the CRC
Age manifestation of the disease was varied in relation
of patient’s gender. The largest number of males was ob
served at the age from 65 to 74 years, which were on 15–
20 years later than females. Females were ill at an earli
er age starting from 25 years. At the age of 25–29 years
were observed 3 (3.4%) females with CRC unlike male
patients — 2 (2.1%) were registrated starting at the age
of 35–39 years. The number of female patients at the age
of 35–39 years and of 40–44 years were 5 (5.6%) and
6 (6.8%) individuals, respectively, exceeded in twice the
number of male patients at the same age — 2 (2.1%) and
3 (3.2%) individuals, respectively. The incidence of CRC
in males at the age of 70–74 years was twice higher, than
in females: 19 (20.2%) male patients and 9 (10.2%) fe
male patients, respectively. According to the data of Bul
letin of the National Cancer Registry in Ukraine, the fre
quency of females at the age of 25–29 years with cancer
of the colon and rectum was higher (1.8/100,000), than
males (0.8/100,000), but at the age of 80–84 years the
frequency of cancer of the same localization was higher in
males (109.8/100,000), than females (22.1/100,000) [1].
The number of male patients aged over 80 years was ex
ceeded the number of female patients: 9 (9.6%) males
and 5 (5.7%) females. Wider range age (25–86 years) of
CRC onset was observed in females, unlike males (35–
82 years). The incidence of CRC after 80 years in females
decreased to the level of the age group of 30–39 years
unlike males: 5 (5.7%) females and 9 (9.6%) males. Ac
cording to the literature data sporadic colon cancer pro
gresses stepwise from adenoma to carcinoma, with a la
tency period that may last decades and with highest in
cidence during advancing age [14], it is conceivable that
tumors start developing slowly before menopause, but
rapidly progress with cessation of ovarian estrogen pro
duction [14, 15]. In the observed group 8 (9.1%) female
patients at the age range of 45–49 years were found, and
the maximum number — 14 (15.9%) females, were found
at the age of 50–54 years. A stable high level of CRC in
cidence (10.0–11.0% of females) was observed in patients
at 55–74 years. It was known that antiproliferative effects
of 17βestradiol are mediated through the estrogen re
ceptor (ER)β, which is the predominant ER subtype in
the human colon mucosa [16]. In addition, there is evi
dence to suggest that the chemopreventive effect of es
trogen against CRC is mediated in part through vitamin D
receptor (VDR)activated antiproliferative intracellular
signaling. Early during tumor progression human colo
nocytes express high levels of the CYP27B1encoded
25hydroxyvitamin D1αhydroxylase, the enzyme that
synthesizes the active vitamin D metabolite, 1,25dihy
doxyvitamin D3 (1,25 (OH)2D3), which when bound to
its cognate receptor, the VDR, effectively inhibits pro
liferation and promotes differentiation in human colon
cancer cells [17]. Estrogens have been shown to increase
VDR and CYP27B1 expression and activity in human
colonocytes. Thus, activation of ERβ causes antitumor
effect. Estrogens increase the potential antiproliferative
effect of vitamin D hormone [17–21]. However, women
are protected from more aggressive cancer in the colon
though not in the rectum until well after menopause. This
likely reflects the differential sensitivity of the mucosa at
these sites against the anticancer effects triggered by ac
tivation of ERβ [22].
The manifestation of the disease occurred in females
at a younger age, ranging from 25 years, that is on 11 years
earlier, than in males. The maximum number of men —
6 (24.0%) patients was observed at the age range of 65–
69 years that more than twice exceeded the number of
women — 4 (11.0%) patients. The number of patients
of both genders in older age (over 75 years) was lower
(5.6%), than in patients without family history (6.8%,
see Fig. 1). The male patients at this age range (Fig. 2)
never found inlike to male patients without the family
history of CRC (6.4%, see Fig. 1).
In probands with «positive» familial anamnesis the
peak age of the disease manifestation was lower by 5 years
for both genders: in males is 65–69 years, and in females
is 45–49 years, compared with age of individuals with
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
107ОНКОЛОГИЯ • Т. 18 • № 2 • 2016 107
out family history (in men is 70–74 years and in women
is 50–54 years). The analysis of distribution on age and
gender of CRC onset in probands with «positive» fami
lial anamnesis for CRC, is shown on Fig. 2.
Males
Females
25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80 and >
0
5
10
15
20
25
30%
Years
Fig. 2. The distribution of males and females by age mani
festation for the CRC with familial anamnesis for the disease
Among the 182 probands «positive» familial anam
nesis was found in 61 (33.5%) patients: in 25 males and
36 females. In 7 (11.5%) relatives of probands the dise
ase repeated in three generations. Recurrence of CRC in
2–3 generations of families allows to confirms an auto
somal dominant mode of inheritance of the disease in
some patients. The frequency of various diseases of co
lon, associated with CRC and family history of this dise
ase, is shown in Fig. 3.
1
2
3
4 5 6
Fig. 3. The frequency of various diseases of colon, associated
with CRC, and «positive» familial anamnesis of this disease:
1 — familial CRC (patients to met 1–2 of Amsterdam crite
ria for Lynch syndrome) — 65.6%; 2 — Lynch syndrome —
14.8%; 3 — FAP — 11.5%; 4 — CRCassociated inflamma
tory bo wel diseases — 4.9%; 5 — MAP — 1.6%; 6 — Peutz —
Jeghers syndrome — 1.6%
It was determined (see Fig. 2) that among patients
with family history of CRC 18 (29.5%) individuals had
monogenic diseases of colon, such as: Lynch syndrome —
9 (14.8%), FAP — 7 (11.5%), MAP — 1 (1.6%) and
Peutz — Jeghers syndrome — 1 (1.6%). Among them
were 7 males and 11 females. Inflammatory bowel dise
ase ulcerative colitis and Crohn’s disease, associated
with CRC, was found in 3 (4.9%) patients with heredi
tary predisposition to CRC. The familial cancer was the
most common in this group of probands and was diag
nosed in 40 (65.6%) patients. According to the literature
data, of common malignancies, CRC has one of the lar
gest proportions of familial cases. Kindred and twin stu
dies estimated that approximately 30% of all CRC cases
are an inherited form of the disease [23]. It is known that
in Lynch syndrome patients there is a different lifetime
risk and earlier age of manifestation for CRC — especial
ly in MSH6 mutation carriers, in men and women [24].
In 25 (41.0%) males and in 36 (59.0%) females «posi
tive» familial anamnesis for CRC was confirmed (p > 0.05).
It was observed 69 (57.0%) males and 52 (43.0%) females
without family history of CRC (p > 0.05). Despite the
lack of a statistically significant difference between the
groups of males and females, probably due to the small
number of patients in groups, the distribution of cancer
cases in the observed families demonstrates the tenden
cy, called the Carter effect [25]. It means that the indi
viduals of gender, which is less affected, have a higher
hereditary predisposition compared with patients of the
gender, which is often affected. It is known that the in
cidence and mortality in men by 30–40% higher than in
women, despite fluctuations depending on age [1, 24].
There was established statistically significant differen
ce of the age of CRC onset regarding the hereditary pre
disposition to the disease. Males and females with family
history of CRC had lower average age of manifestation of
the disease than in patients without a «positive» familial
anamnesis. In male patients with family history of CRC
the average age of the CRC onset was 50.9 ± 2.77 years
that was approximately at 15 years less, than those with
out family history for the disease (66.2 ± 1.10 years). In
women with familial history of CRC the difference of
the average age of cancer onset was 50.9 ± 2.91 years less
more than 9 years, than those without a genetic predis
position to the disease — 60.2 ± 1.72 years (Table 3).
Table 3
Gender differences of average age of CRC onset and hereditary
predisposition to this disease
Gender Family history
of CRC
Average age of CRC
onset (in years),
М ± m
р
Males
(n = 94)
n1= 69 − 66.2 ± 1.10
<0.001
n2 = 25 + 50.9 ± 2.77
Females
(n = 88)
n1 = 52 − 60.2 ± 1.72
<0.01
n2 = 36 + 50.9 ± 2.91
n1 — the number of patients without family history of CRC; n2 — the number
of patients with family history of CRC.
There was not confirmed statistically significant diffe
rence between the average age of CRC onset in patients
of both genders with «positive» familial anamnesis of the
disease. However, it was revealed a statistically significant
difference (p < 0.01) for the average age of the CRC on
set between males (66.2 ± 1.10 years) and females (60.2
± 1.72 years) without family history.
Thus, the study of gender and ageCRC is one of
the urgent problems of modern medicine. A precise un
derstanding of the age of inherited CRCs manifestation
is important for identifying atrisk individuals, impro
ving cancer surveillance and prevention strategies, and
ОНКОЛОГИЯ • Т. 18 • № 2 • 2016
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
108
developing better diagnostic and therapeutic approa
ches. Studies of the cases of familial and inherited colon
cancers have led to recommendations for colon cancer
screening. Furthermore, genetic study among this group
of patients improves our understanding of colon cancer
risk, pathogenesis, and prevention.
CONCLUSIONS
1. Age of the CRC onset was varied in relation of pa
tient’s gender and hereditary predisposition to the dise
ase. In probands with family history of CRC the peak age
of the disease onset was 5 years lower for both genders
(65–69 years in males and 45–49 years in females), com
pared to the age of patients without family history (70–
74 years in males and 50–54 years in females).
2. Among probands with family history of CRC 29.5%
individuals have monogenic cancer syndromes of co
lon, such as: Lynch syndrome, FAP, MAP and Peutz —
Jeghers syndrome. CRCassociated inflammatory bo
wel disease was found in 4.9% patients with familial an
amnesis for CRC.
3. The average age of CRC onset in probands of both
genders with hereditary predisposition to this disease was
the statistically significant lower, than in patients with
out family history.
4. The statistically significant difference for the
ave rage age of the CRC onset between males and fe
males without family history of the disease was revealed.
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ХАРАКТЕРИСТИКА РОЗПОДІЛУ ХВОРИХ
НА КОЛОРЕКТАЛЬНИЙ РАК ЗА ВІКОМ
І СТАТТЮ ЗАЛЕЖНО ВІД СПАДКОВОЇ
ОБТЯЖЕНОСТІ ЦИМ ЗАХВОРЮВАННЯМ
М.Р. Лозинська, О.М. Федота, Л.Ю. Лозинська,
Н.М. Прокопчук, Р.О. Піняжко
Резюме. Мета: провести аналіз розподілу хворих
різної статі за віком маніфестації колоректально-
го раку (КРР) зі спадковою обтяженістю та без об-
тяженості цим захворюванням для виявлення осіб
груп ризику. Об’єкт і методи: аналіз медичної до-
кументації та генеалогічної інформації у 182 хво-
рих на КРР (94 чоловіки і 88 жінок). «Позитивний»
сімейний анамнез КРР підтверджено у 61 пробан-
да: 40 з них відповідали одному–двом Амстердам-
ським критеріям діагностики, 9 — трьом Амстер-
дамським критеріям, 7 — мали сімейний аденома-
тозний поліпоз, 3 — спадкову обтяженість на КРР,
асоційований із запальними захворюваннями кишеч-
нику, та по одному випадку MUTYH-асоційованого
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
109ОНКОЛОГИЯ • Т. 18 • № 2 • 2016 109
поліпозу і синдрому Пейтца — Єгерса. Результа-
ти: вік маніфестації захворювання варіював за-
лежно від статі пацієнтів і спадкової обтяже-
ності. У пробандів із сімейним анамнезом КРР ві-
ковий пік маніфестації захворювання був меншим
на 5 років для обох статей порівняно з віком осіб
без спадкової обтяженості. У пробандів із КРР чо-
ловічої та жіночої статі зі спадковою обтяженіс-
тю цим захворюванням встановлено істотно мен-
ший середній вік маніфестації хвороби, ніж у хворих
чоловіків і жінок без спадкової обтяженості. Між
чоловіками і жінками без спадкової обтяженості
КРР за середнім віком маніфестації хвороби вста-
новлено статистично істотну різницю. Висновок:
встановлення віку маніфестації спадкових варіан-
тів КРР і статевих особливостей пацієнтів із цим
захворюванням є важливим для виявлення осіб груп
ризику, а також для покращення спостереження
за пацієнтами із раком товстої кишки та відпра-
цювання превентивної стратегії для вдосконален-
ня діагностики і лікувальних підходів.
Ключові слова: колоректальний рак, сімейний
анамнез, вік маніфестації хвороби, стать.
Correspondence:
Lozynska M.R.
31А M. Lysenko str., Lviv 79000
SI «Institute of Hereditary Pathology of NAMS
of Ukraine»
Email: maria_lozynska@ukr.net
Submitted: 10.03.2016
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