No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients
Factor VII (FVII) plays an important role in blood coagulation. The role of common polymorphisms influencing the FVII plasma levels in thromboembolic disorders has been evaluated but there is no published data related to the effect of FVII gene polymorphisms on the venous thrombosis risk in cancer....
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irk-123456789-1385952018-06-20T03:04:32Z No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients Eroglu, A. Ozturk, A. Cam, R. Akar, N. Original contributions Factor VII (FVII) plays an important role in blood coagulation. The role of common polymorphisms influencing the FVII plasma levels in thromboembolic disorders has been evaluated but there is no published data related to the effect of FVII gene polymorphisms on the venous thrombosis risk in cancer. Aim: To investigate the association of three common functional polymorphisms in the promoter region of FVII gene: a decanucleotide insertion at position-323 (-323ins10-bp), a G to T substitution at position-401 (-401GT), and a G to A substitution at position-402 (-401GT) with venous thrombosis in cancer patients. Materials and Methods: The study included 60 cancer patients with venous thromboembolism (VTE) (group 1) and 130 cancer patients without VTE (group 2). Genotyping of -323ins10-bp, -401GT, and -402GA polymorphisms in the promoter region of FVII gene was performed by the method of single-strand conformation polymorphism analysis and sequencing. Factor V Leiden (FVL) was also determined in all cases. Results: The frequency of FVL was significantly greater in cancer patients with VTE compared with group 2 patients (p < 0.0001). For each polymorphism of FVII gene, the distributions of genotypes and allele frequencies were not significantly different between two groups of patients (p > 0.05). The results did not change significantly after the exclusion of patients carrying the FVL (p > 0.05). Conclusions: The screening for the -323ins10-bp, -401GT, and -402GA olymorphisms of FVII gene did not contribute to a meaningful diagnostic nvestigation in cancer patients with venous thrombosis. 2010 Article No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients / A. Eroglu, A. Ozturk, R. Cam, N. Akar // Experimental Oncology. — 2010. — Т. 32, № 1. — С. 15-18. — Бібліогр.: 22 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/138595 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions Eroglu, A. Ozturk, A. Cam, R. Akar, N. No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients Experimental Oncology |
| description |
Factor VII (FVII) plays an important role in blood coagulation. The role of common polymorphisms influencing the FVII plasma levels in thromboembolic disorders has been evaluated but there is no published data related to the effect of FVII gene polymorphisms on the venous thrombosis risk in cancer. Aim: To investigate the association of three common functional polymorphisms in the promoter region of FVII gene: a decanucleotide insertion at position-323 (-323ins10-bp), a G to T substitution at position-401 (-401GT), and a G to A substitution at position-402 (-401GT) with venous thrombosis in cancer patients. Materials and Methods: The study included 60 cancer patients with venous thromboembolism (VTE) (group 1) and 130 cancer patients without VTE (group 2). Genotyping of -323ins10-bp, -401GT, and -402GA polymorphisms in the promoter region of FVII gene was performed by the method of single-strand conformation polymorphism analysis and sequencing. Factor V Leiden (FVL) was also determined in all cases. Results: The frequency of FVL was significantly greater in cancer patients with VTE compared with group 2 patients (p < 0.0001). For each polymorphism of FVII gene, the distributions of genotypes and allele frequencies were not significantly different between two groups of patients (p > 0.05). The results did not change significantly after the exclusion of patients carrying the FVL (p > 0.05). Conclusions: The screening for the -323ins10-bp, -401GT, and -402GA olymorphisms of FVII gene did not contribute to a meaningful diagnostic nvestigation in cancer patients with venous thrombosis. |
| format |
Article |
| author |
Eroglu, A. Ozturk, A. Cam, R. Akar, N. |
| author_facet |
Eroglu, A. Ozturk, A. Cam, R. Akar, N. |
| author_sort |
Eroglu, A. |
| title |
No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients |
| title_short |
No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients |
| title_full |
No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients |
| title_fullStr |
No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients |
| title_full_unstemmed |
No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients |
| title_sort |
no significant association between the promoter region polymorphisms of factor vii gene and risk of venous thrombosis in cancer patients |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2010 |
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Original contributions |
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| citation_txt |
No significant association between the promoter region polymorphisms of factor VII gene and risk of venous thrombosis in cancer patients / A. Eroglu, A. Ozturk, R. Cam, N. Akar // Experimental Oncology. — 2010. — Т. 32, № 1. — С. 15-18. — Бібліогр.: 22 назв. — англ. |
| series |
Experimental Oncology |
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2025-07-10T06:08:25Z |
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2025-07-10T06:08:25Z |
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| fulltext |
Experimental Oncology 32, 15–18, 2010 (March) 15
Several hereditary risk factors for venous throm-
boembolism (VTE) have been identified [1]. The
polymorphic variants of genes encoding coagulation
factors have been investigated as risk factors for ve-
nous thrombosis [2]. Among the inherited clotting ab-
normalities, factor V Leiden (FVL) is the most common
cause for venous thrombosis. It is known that factor VII
(FVII) plays an important role in the extrinsic pathway
of blood coagulation. Its coagulant activity is identified
as a potential risk factor for venous or arterial throm-
bosis. Several studies have provided the evidence for
associations between some common polymorphisms
of FVII gene and FVII blood levels [3–8]. However, other
authors have not supported this observation [9].
Three common polymorphisms of the promoter
region in FVII gene locus; a decanucleotide insertion
at position -323 (-323ins10-bp), a G to T substitution
at position -401 (-401GT), and a G to A substitution
at position -402 (-402GA) have been described and
reported to be associated with FVII blood levels. The
-323ins10-bp has been extensively studies in rela-
tion to FVII plasma level (3–6, 9). It is proposed that
-323ins10bp polymorphism may influence the rate of
transcription of FVII gene. The -323ins10bp is function-
ally relevant; the rare insertion allele of 10-bp reduces
the promoter activity, as compared with the common
allele [10]. This insertion allele is related to low blood
levels of FVII. According to van’t Hooft et al. [4] study,
-401GT polymorphism is strong linkage disequilibrium
with the -323ins10-bp polymorphism.
The -401 T allele was associated with significantly
lower plasma levels of FVII than the common -401 G allele,
but the rare -402 A allele was associated with significantly
higher FVII levels than the common -402 G allele.
On the other hand, there has been controversy
whether the genetic variations in blood FVII levels influ-
ence the development of VTE [8, 11, 12]. High blood
levels of FVII may be related to hypercoagulable state
and certain mutations in FVII gene locus contribute to
the variability in plasma FVII activity. Several studies have
failed to find any association of FVII gene polymorphisms
and venous thrombosis, but not arterial thrombosis [7, 8,
11–13]. A few reports have suggested that those alleles
associated with low levels of FVII could play a protective
role against myocardial infarction [5, 6]. Other studies,
however, failed to detect such as influence [14, 15].
Cancer patients have an increased risk of VTE.
Recently we have demonstrated the significant as-
sociation between FVL and the risk of VTE in patients
with cancer [16, 17]. Whether the polymorphism of FVII
gene is related to an increased risk of VTE in cancer is
still an open question. There are only a few published
studies about the effect of FVII gene polymorphisms on
the risk of idiopathic venous thrombosis [7, 8, 11–13].
The published studies have not included in cases with
secondary VTE due to acquired risk factors including
malignancy. Koster et al. [11] reported the first study
NO SIGNIFICANT ASSOCIATION BETWEEN THE PROMOTER
REGION POLYMORPHISMS OF FACTOR VII GENE AND RISK
OF VENOUS THROMBOSIS IN CANCER PATIENTS
A. Eroğlu1, *, A. Öztürk2, R. Çam3, N. Akar4
1Department of General Surgery, Ankara University Medical School, Ankara 06590, Turkey
2Department of Pediatric Molecular Genetics, Ankara University Medical School, Ankara 06590, Turkey
3Bodrum Private Hospital, Bodrum 48400, Turkey
4Department of Pediatric Molecular Genetics, Ankara University Medical School, Ankara 06590, Turkey
Factor VII (FVII) plays an important role in blood coagulation. The role of common polymorphisms influencing the FVII plasma
levels in thromboembolic disorders has been evaluated but there is no published data related to the effect of FVII gene polymor-
phisms on the venous thrombosis risk in cancer. Aim: To investigate the association of three common functional polymorphisms
in the promoter region of FVII gene: a decanucleotide insertion at position -323 (-323ins10-bp), a G to T substitution at position
-401 (-401GT), and a G to A substitution at position -402 (-401GT) with venous thrombosis in cancer patients. Materials and Me-
thods: The study included 60 cancer patients with venous thromboembolism (VTE) (group 1) and 130 cancer patients without VTE
(group 2). Genotyping of -323ins10-bp, -401GT, and -402GA polymorphisms in the promoter region of FVII gene was performed
by the method of single-strand conformation polymorphism analysis and sequencing. Factor V Leiden (FVL) was also determined
in all cases. Results: The frequency of FVL was significantly greater in cancer patients with VTE compared with group 2 patients
(p < 0.0001). For each polymorphism of FVII gene, the distributions of genotypes and allele frequencies were not significantly
different between two groups of patients (p > 0.05). The results did not change significantly after the exclusion of patients carrying
the FVL (p > 0.05). Conclusions: The screening for the -323ins10-bp, -401GT, and -402GA polymorphisms of FVII gene did not
contribute to a meaningful diagnostic investigation in cancer patients with venous thrombosis.
Key Words: cancer, factor VII, gene, polymorphism, promoter region, thrombosis.
Received: November 26, 2009.
*Correspondence: Fax: 903123093989
E-mail: aydaneroglu@hotmail.com
Abbreviations used: CI — confidence intervals; DVT — deep venous
thrombosis; FVII — factor VII; FVL — factor V Leiden; OR — odd
ratio; SSCP — single-strand conformation polymorphism; VTE —
venous thromboembolism.
Exp Oncol 2010
32, 1, 15–18
16 Experimental Oncology 32, 15–18, 2010 (March)
that examined the risk of venous thrombosis in relation
to Msp1 polymorphism of FVII gene. The polymor-
phism was not associated with the risk of deep venous
thrombosis (DVT). Besides, no significant association
of FVII plasma level with DVT was found.
The thrombotic role of several polymorphisms of
genes encoding haemostatic factors has been inves-
tigated in cancer patients [16, 17]. Although FVL is an
important risk factor for venous thrombosis in cancer,
the findings are controversial. If the FVII plays a role as
a risk factor for VTE, it can be important to investigate
the association between its functional polymorphism
and venous thrombosis in cancer patients. In light of
the postulation, we have evaluated the possible cor-
relation of promoter region polymorphisms of FVII gene
with risk of VTE in cancer patients.
MATERIALS AND METHODS
The study population has been described previously
[16, 17]. Briefly, two groups of cancer patients were
enrolled in the study. Group I consisted of 60 cancer
patients with VTE (one patient had thrombosis of the
axillary and subclavian vein; two had pulmonary embo-
lism without DVT; other patients had DVT of the lower
extremity). Tumor location in this group was as follows:
breast (n = 16), lung (n = 17), larynx (n = 2), brain (n = 2),
digestive system (n = 11), genitourinary system (n = 3),
extremities sarcoma (n = 4), other (n = 5). Group 2 was
composed of 130 cancer patients with tumors of breast
(n = 76), lung (n = 24), digestive tract (n = 6), larynx (n =
3), brain (n = 5), sarcoma (n = 5), genitourinary system
(n = 3), others (n = 8), who had no history of thrombo-
embolic disease during the cancer therapy or follow-up
period. In general, tumor stages according to TNM clas-
sification were similar in both groups. For example, the
distribution of tumor stage for breast cancer in groups
1 and 2 was as follows: early stage (stage I/II) in 8 pa-
tients and advanced stage in 8 patients in group 1; early
stage in 39 and advanced stage in 37 patients in group
2. All patients with breast cancer in two groups had in-
vasive tumors. The lung cancer patients in both groups
had advanced stage of disease. Five of 11 patients with
digestive system cancer in group 1 had metastasis.
Three of 6 patients with digestive system cancer in
group 2 had stage 4 cancer. Before the collection of
peripheral blood, all patients gave informed consent to
participate in this study. Ethical committee approval was
obtained for molecular studies on thrombosis.
DNA was isolated from peripheral blood lympho-
cytes by the standard phenol-chloroform method.
Genomic DNA was amplified by polymerase chain
reaction (PCR). Genotyping was performed by single-
strand conformation polymorphism (SSCP) analysis
and sequencing of all identified patterns. The primer
design was based on the sequence of the promoter
region of FVII gene. The 323ins10-bp, -401GT, 402GA
polymorphisms in the promoter region of FVII gene
were amplified [3, 4, 10, 18]. The PCR reaction started
with 5 min at 95 °C and was continued by 34 cycles of
94 °C/1 min, 60 °C/1 min, 72 °C/1 min, and final exten-
sion of 10 min at 72 °C (Biometra, Germany). The PCR
samples were run on 2% agarose gel.
SSCP was carried out using the following primers: F
5’-GGC CTG GTC TGG AGG CTC TCT TC-3’; R 5’-CGC
TGG CAA CAA AAC CGT CCG CTC-3’ [15, 18]. The
amplified DNA fragment was 214 bp for SSCP. The PCR
products were denatured at 99 °C for 7 min and then
the resulting single-stranded DNA was loaded on 8%
polyacrylamide gel. Electrophoresis was performed
with a sequencing apparatus at 130 V of constant
power at 4 °C for 10 to 12 h depending on the fragment
size. After electrophoresis, gel was silver stained and
was visualized under ultraviolet light.
A 315-bp DNA fragment was amplified for DNA
sequencing using the following specific primers:
F 5’-GTA AGA TGT GGA CCG CTG GA-3’ and R 5’-ACA
AAA CCG TCC GCT CTG-3’. PCR was carried out after
choosing the different band profiles of SSCP analysis.
Prior to sequencing, the samples were purified
by using a PCR purification kit (Agencourt, Ampure,
Beckman Coulter, USA) and then the DNA sequence
analysis was performed using an automatic sequencer
[18] (Beckman Coulter CEQ 8000, Beckman Coulter,
Fullerton, California, USA).
In addition to these polymorphisms, FVL was
determined in all cases [17]. The frequencies of the
alleles and genotypes associated with each of three
polymorphisms of FVII gene and FVL between two
groups were compared by chi-square or two-sided
Fisher exact test, as appropriate. Haplotype analysis
for FVII gene was also carried out and the distribution
of the haplotypes between two groups was compared.
Odds ratios (OR) were calculated as estimate of
relative risk, together with 95% confidence intervals
(95% CI). All the statistical analyses were also per-
formed after cases with FVL were excluded from the
study. All observed genotype and allele frequencies
were tested for compliance with Hardy-Weinberg
equilibrium. Statistical significance was determined
as p < 0.05. The statistical analysis was made using
SPSS software (SPSS Inc., Chicago, IL).
RESULTS
In all groups, the genotype distributions and allele
frequencies were in Hardy-Weinberg equilibrium. The
genotypes and allelic frequencies of the -323ins 10-bp,
-401GT, -402GA polymorphisms among the patients
with and without VTE were summarized in Table 1. The
frequencies of these polymorphisms were not signifi-
cantly different in the two groups (p > 0.05). Interes-
tingly, two mutations in the promoter region of FVII gene
(-401GT and -323ins10-bp) occurred simultaneously.
As shown in Table 2, there was no significant dif-
ference in the distribution of six haplotypes between
group 1 and 2 patients.
For FVL, we observed the mutation in 25% (15 of 60)
and 1.54% (2 of 130) of patients in group 1 and group 2,
respectively. This difference between the two groups
was found to be statistically significant (p < 0.0001).
Experimental Oncology 32, 15–18, 2010 (March) 17
Table 1. Distribution of three common polymorphisms, -323 ins 10-bp,
-401 G/T, and -402 G/A in the promoter region of FVII gene in cancer
patients with (group 1) and without venous thrombosis (group 2)
FVII
Polymorphisms
Group 1
(n = 60)
Group 2
(n = 130) p value
-323 ins10-bp
w/w 33 (55%) 80 (61.5%)
ins/w 25 (41.6%) 45 (34.6%) 0.9
ins/ins 2 (3.3%) 5 (3.8%)
w allele 0.76 0.79
ins allele 0.24 0.21
-401 G/T
GG 33 (55%) 80 (61.5%)
GT 25 (41.6%) 45 (34.6%) 0.9
TT 2 (3.3%) 5 (3.8%)
G allele 0.76 0.79
T allele 0.24 0.21
-402 G/A
GG 48 (80%) 89 (68.5%)
GA 11 (18.3%) 34 (26.2%) 0.7
AA 1 (1.6%) 7 (5.4%)
G allele 0.89 0.815
A allele 0.11 0.185.
In Tables 1, 3: Ins — insertion; w — wild type.
Table 2. Distribution of haplotype of FVII in patients with (group 1) and
without thrombosis (group 2)
Haplo type Group 1
(n = 60)
Group 2
(n = 130) OR (CI) p value
I 25 (41.6%) 46 (35.4%) 1
II 1 (1.6%) 7 (5.4%) 0.3 (0.03–2.3) 0.6
III 7 (11.6%) 27 (20.8%) 0.5 (0.2–1.3) 0.2
IV 21 (35%) 38 (29.2%) 1 (0.5–2) 0.9
V 4 (6.6%) 7 (5.4%) 1 (0.3–3.9) 0.8
VI 2 (3.3%) 5 (3.8%) 0.7 (0.1–4.1) 0.9
I: -402GG/-401GG/-323w/w; II: -402AA/-401GG/-323w/w;
III: -402GA/-401GG/-323w/w; IV: -402GG/-401GT/-323ins/w;
V: -402GA/-401GT/-323ins/w; VI: -402GG/-401TT/-323ins/ins
Notes: OR — odds ratio; CI — 95% confidence interval.
We next calculated the prevalence of the -323ins10-
bp, -401GT, -402GA polymorphisms in two groups pa-
tients after excluding FVL mutation positive patients.
No difference was also detected in the distribution of
-323ins10-bp,-401GT, -402GA genotypes in cancer
patients with VTE versus those without VTE (p > 0.05).
Their allelic frequencies between two groups were
also found to be statistically insignificant (Table 3). In
addition, the haplotype frequencies showed a similar
distribution among cancer patients with and without
VTE (p > 0.05) (data not shown).
Table 3. Prevalence of -323 ins 10-bp, -401 G/T, and -402 G/A polymorphisms
of FVII gene in cancer patients with (group 1) and without venous thrombosis
(group 2) after exclusion of patients carriers of FVL
FVII
Polymorphisms
Group 1
(n = 45)
Group 2
(n = 128) p value
-323 ins10-bp
w/w 21 (46.6%) 79 (61.7%)
ins/w 22 (48.8%) 44 (34.4%) 0.8
ins/ins 2 (4.4%) 5 (3.9%)
w allele 0.71 0.79
ins allele 0.29 0.21
-401 G/T
GG 21 (46.6%) 79 (61.7%)
GT 22 (48.8%) 44 (34.4%) 0.8
TT 2 (4.4%) 5 (3.9%)
G allele 0.71 0.79
T allele 0.29 0.21
-402 G/A
GG 37 (82.2%) 87 (67.9%)
GA 7 (15.5%) 34 (26.5%) 0.8
AA 1 (2.2%) 7 (5.5%)
G allele 0.9 0.813
A allele 0.1 0.187
DISCUSSION
Thrombosis is one of the most common compli-
cations in patients with malignant disease [19, 20].
The pathogenesis of haemostatic disorders in cancer
reflects the interaction of different mechanisms inclu-
ding cancer-related factors such as venous stasis, the
effects of treatment, especially chemotherapy and
patient-specific factors such as thrombophilic status
of cancer patients, acquired or congenital disorders
of hemostasis. Several molecules of the coagulation
and fibrinolytic systems are activated in cancer. Cancer
cells can also produce TF and cancer procoagulants
which activated the coagulation system [20].
FVII plays a key role in the extrinsic pathway of blood
coagulation. High plasma FVII levels can be associated
with venous or arterial thrombosis. The polymorphisms
in the FVII gene may contribute to the variations in
plasma levels of FVII. Therefore, it may be postulated
that these polymorphisms precipitate venous thrombo-
sis. Previous studies demonstrated that the rare alleles
of the polymorphisms at positions -401 and -402 were
related to marked changes in the rate of FVII gene
transcription [4]. The -323ins10-bp polymorphism was
directly related to the decrease in transcription [10].
The common polymorphisms in the promoter
region of FVII gene may influence FVII blood levels
because they may modulate its transcription [4, 9, 10].
Corral et al. [21] showed that carriers of the -323ins
allele had an increased risk for intracranial hemorrhage
and they found statistically significant differences in
the prevalence of FVII -323ins10-bp polymorphism
between patients and controls.
On the other hand, some studies have investigated
the role of common polymorphisms influencing the
FVII plasma levels in thrombotic disorders with con-
flicting results. There have been a few studies which
evaluate the relationship between idiopathic VTE and
some common polymorphisms of FVII gene [7, 8,
11–13]. The studies failed to show an association be-
tween the risk of VTE and the polymorphisms known
to modulate blood FVII levels. Corral and colleagues
[12] demonstrated no significant association between
-323ins10-bp polymorphism and the risk of DVT. More
recently, Folsom et al. [8] have shown that FVII 402GA
polymorphism is not associated with VTE occurrence.
It should be emphasized that the published studies
have not included in cases with secondary VTE due to
acquired risk factors including malignancy.
To our knowledge, the present study is the first to ad-
dress the potential association between venous throm-
bosis and the common promoter region polymorphisms
of FVII gene in cancer patients. Our studies showed that
the promoter region polymorphisms were not strong
determinants of venous thrombosis in cancer patients.
According to some previous studies, the -401GT
polymorphism is the linkage disequilibrium with
-323ins10-bp polymorphism [3, 4, 10]. In agreement
with the reports, 401GT polymorphism showed com-
plete allelic association with -323ins10-bp polymor-
phism in our series.
18 Experimental Oncology 32, 15–18, 2010 (March)
FVL is a well-established risk factor in the deve-
lopment of DVT [1, 2]. It is the most common genetic
defect causing thrombosis among Caucasians. In ge-
neral, the risk of venous thrombosis is 5–10-fold higher
in cases carrying heterozygous and 50–80-fold higher in
cases with homozygous for FVL. However, the role of he-
reditary thrombophilia in cancer patients with VTE is still
unclear [16, 17, 19]. Some authors have been evaluated
the role of FVL mutation on the thrombosis risk in malig-
nancy [17]. Previously, we demonstrated a significant
association between FVL and venous thrombosis risk
in cancer patients [16, 17]. In this study, the frequency
FVL in cancer patients with VTE was significantly higher
than in those without VTE. The high prevalence of FVL in
cancer patients with thrombosis can be associated with
the high frequency among healthy Turkish population
[22]. After exclusion of patient carriers of FVL, the rela-
tionship between the FVII gene polymorphisms and VTE
was evaluated in our series. When the statistical analysis
was also performed, the same insignificant results were
observed. Accordingly it can be suggested that the
screening for FVII polymorphisms does not contribute to
a meaningful diagnostic investigation of thrombophilia in
cancer patients with VTE.
Although the present study is the first to evalu-
ate the association between venous thrombosis risk
and the promoter region polymorphisms of FVII gene
among cancer patients, there are a few limitations.
Firstly, we have not determined FVII plasma levels in
our cases. Other limitation is its small size. Another
limitation of our study is that patients with different
types of cancer were enrolled. Therefore the interpre-
tation of the results can be complicated.
In conclusion, our study has suggested that three
promoter polymorphisms of FVII gene; 323ins10-bp,
-401GT, and -402GA are not contributing variants to VTE
occurrence in cancer patients. FVL is the significant risk
factor for the development of VTE but there is no additive
effect of these polymorphisms of FVII gene in cancer.
However, further larger studies including different ethnic
population are required to better clarify the association
of FVII polymorphisms with the thrombosis risk.
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