SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population
A variable number of tandem repeats (VNTR) polymorphism in regulatory region of SMYD3 coding for histone methyltransferase has been shown to be associated with colorectal cancer, hepatocellular carcinoma (HCC), and breast cancer in Japanese population. Aim of the study is to investigate the potentia...
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| Veröffentlicht in: | Experimental Oncology |
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| Datum: | 2007 |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2007
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| Zitieren: | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population / X.Q. Wang, X. Miao, Q. Cai, M.M. Garcia-Barcelo, S.T. Fan // Experimental Oncology. — 2007. — Т. 29, № 1. — С. 71-73. — Бібліогр.: 7 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1859803550648893440 |
|---|---|
| author | Wang, X.Q. Miao, X. Cai, Q. Garcia-Barcelo, M.M. Fan, S.T. |
| author_facet | Wang, X.Q. Miao, X. Cai, Q. Garcia-Barcelo, M.M. Fan, S.T. |
| citation_txt | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population / X.Q. Wang, X. Miao, Q. Cai, M.M. Garcia-Barcelo, S.T. Fan // Experimental Oncology. — 2007. — Т. 29, № 1. — С. 71-73. — Бібліогр.: 7 назв. — англ. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| description | A variable number of tandem repeats (VNTR) polymorphism in regulatory region of SMYD3 coding for histone methyltransferase has been shown to be associated with colorectal cancer, hepatocellular carcinoma (HCC), and breast cancer in Japanese population. Aim of the study is to investigate the potential association between the functional SMYD3 tandem repeats polymorphism and HCC in Chinese population. Material and Methods: The case-control study included 200 HCC patients and 261 healthy controls. The VNTR polymorphism in the promoter of SMDY3 was genotyped by PCR and direct-sequencing analysis. Odds ratio and 95% confidence interval were used to estimate the association between the polymorphisms and risk of HCC. Results: The allele frequencies for SMYD3 2 and 3 repeats were 15.71% and 84.29% among controls; and 12.75%, and 87.25% among cases (P = 0.22). The odds ratio for 3/3 versus 2/2 and 2/3 genotypes was 1.30 (P = 0.18). The frequencies of 3 alleles were not increased with HCC stage increased (trend test, P = 0.45). Conclusion: SMYD3 polymorphism is not associated with the occurrence and metastasis of HCC in Chinese population.
Известно, что полиморфизм тандемных повторов (VNTR) в регуляторном участке гена SMYD3,кодирующем метилтрансферазу
гистонов, ассоциирован с развитием рака прямой кишки, карциномы печени (HCC) и рака молочной железы и является популяционно-зависимой
характеристикой. Цель работы состояла в исследовании возможной связи междуVNTR Геном SMYD3 и развитием
HCC у населения Китая. Материалы и методы: исследование типа “случай-контроль” проводили с участием 200 пациентов с
HCC и 261 здорового донора. Полиморфизм VNTR в промоторной области гена SMDY3генотипировали методами PCR. Для оценки связи между полиморфизмом и риском развитияHCC использовали отношение шансов (OR) и 95%
доверительные интервалы. Результаты: частота аллелей для повторов SMYD3 2 и 3 составила 15,71 и 84,29% в контрольной
группе и 12,75 и 87,25% — в группе больных (P = 0,22). OR Генотипов 3/3 versus 2/2 и 2/3 составило 1,30 (P = 0.18). Частота
3 аллелей не возрастала при повышении стадии заболевания (P = 0,45). Выводы: полиморфизм гена SMYD3 не ассоциирован
с развитием и метастазированием HCC у населения Китая.
|
| first_indexed | 2025-12-07T15:15:35Z |
| format | Article |
| fulltext |
Experimental Oncology ���� ������� ���� ��arc��� ������ ������� ���� ��arc��� ���arc��� ���� �� ��
SMYD3�� a �istone met�yltransferase�� was first
found upregulated in �uman colorectal cancer �CRC��
and �epatocellular carcinoma �HCC�� [�]. Its over-
expression promotes cell proliferation particularly in
tumors�� indicating t�at SMYD3 may play an important
role in carcinogenesis [�]. Recently�� Tsuge et al. [�]
reported a variable number of t�e tandem repeats
�VNTR�� polymorp�ism CCGCC in t�e 5ʹ flanking re-
gion of SMYD3�� w�ic� is a binding site of E�F-�. T�e
E�F-�-binding affinity is �ig�er to t�ree repeats and
results in an increased promoter activity compared
wit� t�e two repeats. Furt�ermore�� t�e t�ree repeats
�ave been identified as a �ig�-risk allele associated
wit� CRC�� HCC�� and breast cancer in a Japanese
population [�]. However�� t�e results from ot�er study
were not consistent. For example�� t�e association of
�/� polymorp�ism of SMYD3 could not be found wit�
bot� familial breast cancer and �ig�-risk familial breast
cancer cases [�]. Genetic disorders are complex to
certain diseases�� particularly for cancer�� and genetic
susceptibility to disease may vary among populations
due to allele differences in bot� frequencies and com-
position as illustrated by t�e recent data generated by
t�e Hap�ap project [4]. To investigate t�e potential
association between t�e functional SMYD3 tandem
repeats polymorp�ism and HCC in t�e C�inese popu-
lation�� we conducted t�is case-control study among
��� HCCs and �6� �ealt�y controls.
Subjects and samples. T�is study included
��� HCC patients and �6� �ealt�y controls. All sub-
jects were genetically unrelated et�nic Han C�inese.
Patients wit� HCC were newly diagnosed based on
pat�ological analyses and classified according to t�e
tumor-node-metastasis classification [5] at Queen
�ary Hospital�� Hong Kong. Population controls were
partially from �ealt�y blood donors randomly col-
lected from Red Cross of Hong Kong and partially
from �ealt�y individuals in t�e same period as t�e HCC
cases were collected and most of t�em were enrolled
in ot�er previous studies of our department [6]. T�e
study was approved by t�e local Institutional Review
Board. �ean age �± SD�� and gender proportion in
eac� group were as follows: HCC�� 54.44 ± ��.8���
and 8�.5% male; controls�� 44.�� ± ��.���� and 5�.�%
male. Of t�e HCC patients�� 85% were �epatitis B virus
positive w�ereas 6% were �epatitis C virus positive.
Among t�e ��� HCC patients�� t�e distribution of tu-
mor-node-metastasis stage I�� II�� II�� and IV were ��%��
�6%�� ��.5%�� and �.5%�� respectively. Genomic DNA
was extracted from t�e perip�eral blood leukocytes
using t�e QIAamp blood kit �Qiagen�� Valencia�� CA��
according to t�e manufacturer’s instructions.
VNTR polymorphism of SMDY3. T�e VNTR poly-
morp�ism in t�e promoter of SMDY3 was genotyped
by PCR and direct-sequencing analysis. Primers used
for PCR VNTR DNA fragments were t�e same as de-
scribed previously [�]. T�e resulting PCR fragments
were t�en subjected to DNA sequencing analysis by an
ABI ���� genetic analyzer �Applied Biosystems�� Foster
City�� CA�� using t�e BigDye Terminator �v�.���.
Statistical analysis. T�e association between t�e
polymorp�isms and risk of HCC was estimated using
odds ratio and its �5% confidence interval�� w�ic�
were calculated by unconditional logistic regression
and adjusted for age and gender. All analyses were
performed wit� Statistical Analysis System software
�version 6.��; SAS Institute�� Cary�� NC��.
T�e distribution of t�e VNTR polymorp�ism of
SMYD3 in t�is study is listed in Table �. T�e allele
frequencies for SMYD3 � repeats and � repeats were
�5.��% and 84.��% among t�e �6� controls; and
��.�5%�� and 8�.�5% among t�e ��� HCC cases.
T�ese differences were not statistically significant
SMYD3 tandem repeats polymorphism is not associated
with the occurrence and metastasis of hepatocellular
carcinoma in a chinese population
X.Q. Wang*, X. Miao, Q. Cai, M.M. Garcia-Barcelo, S.T. Fan
Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
A variable number of tandem repeats (VNTR) polymorphism in regulatory region of SMYD3 coding for histone methyltransferase
has been shown to be associated with colorectal cancer, hepatocellular carcinoma (HCC), and breast cancer in Japanese population.
Aim of the study is to investigate the potential association between the functional SMYD3 tandem repeats polymorphism and HCC in
Chinese population. Material and Methods: The case-control study included 200 HCC patients and 261 healthy controls. The VNTR
polymorphism in the promoter of SMDY3 was genotyped by PCR and direct-sequencing analysis. Odds ratio and 95% confidence
interval were used to estimate the association between the polymorphisms and risk of HCC. Results: The allele frequencies for SMYD3
2 and 3 repeats were 15.71% and 84.29% among controls; and 12.75%, and 87.25% among cases (P = 0.22). The odds ratio for 3/3
versus 2/2 and 2/3 genotypes was 1.30 (P = 0.18). The frequencies of 3 alleles were not increased with HCC stage increased (trend test,
P = 0.45). Conclusion: SMYD3 polymorphism is not associated with the occurrence and metastasis of HCC in Chinese population.
Key Words: SMYD3, polymorphism, hepatocellular carcinoma.
Received: December 29, 2006.
*Correspondence: Fax: 852-28199634
�-mai�: x��an�����cc.���.���-mai�: x��an�����cc.���.��
Abbreviations used: HCC — �epatoce����ar carcinoma;
VNTR — variab�e n�mber of tandem repeats.
Exp Oncol ����
���� ��� �����
short communication
�� Experimental Oncology ���� ������� ���� ��arc���
�P = �.����. T�e frequency of �/� genotype was �5.5%
in HCC group and 6�.�% in control group. T�e odds
ratio of �/� genotype compared wit� �/� or �/� geno-
type was �.�� ��5% confidence interval�� �.8���.�6����
w�ic� was not statistically significant �P = �.�8��. From
bot� allele and repeat frequencies of SMYD3�� t�ere
was no significant difference between control and
HCC group. Furt�ermore�� we analyzed t�e correla-
tion between t�e SMYD3 genotype and metastasis
of HCC �Table ����� but t�e distributions of SMYD3 �/�
genotype among different stages of HCC were similar
���.5%�� ��.�%�� and �4.�% in stages I�� II�� and III + IV��
respectively; Pfor trend = �.45��.
Table 1. SMYD3 po�ymorp�ism and HCC ris�
SMYD3 Contro�s (n = 261) Cases (n = 200) Odds ratio (95% CI) P va��en (%) n (%)
2/2 2 (0.8) 2 (1.0) 1.002/3 78 (29.9) 47 (23.5)
3/3 181 (69.3) 151 (75.5) 1.30 (0.81–2.06) 0.180
2 a��e�e 82 (15.71) 51 (12.75) 1
3 a��e�e 440 (84.29) 349 (87.25) 1.28 (0.86–1.89) 0.220
Table 2. SMYD3 �enotype and a��e�e fre��encies amon� patients �it�
different t�mor sta�es
St�dy �ro�p Tota� s�bjects 2/2 or 2/3 3/3a
No (%) No (%) No (%)
T�mor-node-metastasis-sta�e
I 78 (39.0) 16 (20.5) 62 (79.5)
II 52 (26.0) 15 (28.8) 37 (71.2)
III + IV 70 (35.0) 18 (25.7) 52 (74.3)
aP for trend = 0.450.
VNTR polymorp�ism of SMYD3 �as been firstly
reported to be a susceptibility factor in several �uman
cancers including HCC in t�e Japanese population
[�]. However�� t�e results from ot�er study were not
consistent. �ost recently�� Frank et al. [�] did not found
t�e association of �/� polymorp�ism of SMYD3 wit�
bot� familial breast cancer and �ig�-risk familial breast
cancer cases. T�e present study revealed t�at t�ere
were no statistically significant differences of SMYD3
VNTR polymorp�ism in allele and genotype frequen-
cies between HCC patients and �ealt�y controls. In
addition�� we did not find any correlations between t�e
SMYD3 polymorp�ism and different stages of HCC
disease. T�ese results indicated t�at SMYD3 VNTR
polymorp�ism is not associated wit� HCC in terms of
HCC risk and disease development.
We’d like to notice t�at our data are controversial to
t�оse of Japanese group [�]. One of t�e possibilities
is t�at differences of a genetic polymorp�ism as a risk
factor in two populations may be affected by various
gene-environment interactions during cancer develop-
ment. For example�� geograp�ical differences in HCC
incidence partially reflect variations of viral infection
[�]. In Japan�� �epatitis C virus-associated HCC inci-
dence is ��%�� w�ereas �epatitis B virus ���%�� is t�e
major cause of liver c�ronic infection leading to HCC in
Sout� Asia including Hong Kong [�]. In our study�� 85%
of t�e HCC patients were �epatitis B virus positive and
only 6% were �epatitis C virus positive. T�erefore�� it
would be of interest to investigate w�et�er t�e role of
SYMD3 polymorp�ism in carcinogenesis is dependent
on t�e type of viral infection in HCC.
In conclusion�� t�ere was found no association of
SMYD3 tandem repeats polymorp�ism wit� HCC oc-
currence and metastasis in t�e C�inese population.
T�is is t�e first null report in HCC and more indepen-
dent studies mig�t be needed to verify t�e association
between t�is polymorp�ism and cancer in different
populations.
acknowledgements
T�is study was supported by Sun C.Y. Researc�
Foundation for Hepatobiliary and Pancreatic Surgery
of t�e University of Hong Kong.
references
1. Hamamoto R, Furukawa Y, Morita M, Iimura Y, Sil-
va FP, Li M, Yagyu R, Nakamura Y. SMYD3 encodes a histone
methyltransferase involved in the proliferation of cancer cells.
Nat Cell Biol 2004; 6: 731–40.
2. Tsuge M, Hamamoto R, Silva FP, Ohnishi Y, Chayama K,
Kamatani N, Furukawa Y, Nakamura Y. A variable number of
tandem repeats polymorphism in an E2F-1 binding element
in the 5´ flanking region of SMYD3 is a risk factor for human
cancers. Nat Genet 2005; 37: 1104–7.
3. Frank B, Hemminki K, Wappenschmidt B, Klaes R,
Meindl A, Schmutzler RK, Bugert P, Untch M, Bartram CR,
Burwinkel B. Variable number of tandem repeats polymor-
phism in the SMYD3 promoter region and the risk of familial
breast cancer. Int J Cancer 2005; 118: 2917–8.
4. Goldstein DB, Cavalleri GL. Understanding human
diversity. Nature 2005; 437: 1241–2.
5. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM,
Haller DG, Morrow M. AJCC cancer staging handbook:
TNM classification of malignant tumors, 6th ed. New York:
Springer, 2002.
6. Chan VS, Chan KY, Chen Y, Poon LL, Cheung AN,
Zheng B, Chan KH, Mak W, Ngan HY, Xu X, Screaton G,
Tam PK, Austyn JM, Chan LC, Yip SP, Peiris M, Khoo US,
Lin CL. Homozygous L-SIGN (CLEC4M) plays a protec-
tive role in SARS Coronavirus infection. Nat Genet 2006;
38: 38–46.
7. Llovet JM, Burroughs A, Bruix J. Hepatocellular carci-
noma: Lancet 2003; 362: 1907–17.
Experimental Oncology ���� ������� ���� ��arc��� ������ ������� ���� ��arc��� ���arc��� ���� �� ��
Отсутствие связи между пОлимОрфизмОм
тандемных пОвтОрОв SMYD33 и вОзникнОвением
и метастазирОванием карцинОмы печени
у населения китая
Известно, что полиморфизм тандемных повторов (VNTR) в ре��л�торном �част�е �енаVNTR) в ре��л�торном �част�е �ена) в ре��л�торном �част�е �ена SMYD3,3, �одир�ющем метилтрансфераз�
�истонов, ассоциирован с развитием ра�а пр�мой �иш�и, �арциномы печени (HCC)ира�амолочной�елезыи�вл�етс�поп�л�цион-HCC)ира�амолочной�елезыи�вл�етс�поп�л�цион-) и ра�а молочной �елезы и �вл�етс� поп�л�цион-
но-зависимой хара�теристи�ой. Цель работы состо�ла в исследовании возмо�ной св�зи ме�д� VNTR �еномVNTR �еном �еном SMYD33 и развитием
HCC � населени� Кита�.. Материалы и методы: исследование типа “сл�чай-�онтроль” проводили с �частием 200 пациентов с
HCC и 261 здорово�о донора. �олиморфизм VNTR в промоторной области �ена и 261 здорово�о донора. �олиморфизм VNTR в промоторной области �енаVNTR в промоторной области �ена в промоторной области �ена SMDY33 �енотипировали методами PCR и пр�мо�оPCR и пр�мо�о и пр�мо�о
се�венировани�. Дл� оцен�и св�зи ме�д� полиморфизмом и рис�ом развити� HCC использовали отношение шансов (OR) и 95%HCC использовали отношение шансов (OR) и 95% использовали отношение шансов (OR) и 95%OR) и 95%) и 95%
доверительные интервалы. Результаты: частота аллелей дл� повторов SMYD3SMYD33 2 и 3 составила 15,71 и 84,29% в �онтрольной
�р�ппе и 12,75 и 87,25% — в �р�ппе больных (P = 0,22). OR �енотипов 3/3OR �енотипов 3/3 �енотипов 3/3 versus 2/2 и 2/3 составило 1,30 (P = 0.18). Частота
3 аллелей не возрастала при повышении стадии заболевани� (P = 0,45). Выводы: полиморфизм �ена SMYD33 не ассоциирован
с развитием и метастазированием HCC � населени� Кита�.HCC � населени� Кита�. � населени� Кита�.
Ключевые слова: SMDY3,SMDY3,3, полиморфизм, �арцинома печени.
Copyri��t © �xperimenta� Onco�o�y, 2007
|
| id | nasplib_isofts_kiev_ua-123456789-138565 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T15:15:35Z |
| publishDate | 2007 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Wang, X.Q. Miao, X. Cai, Q. Garcia-Barcelo, M.M. Fan, S.T. 2018-06-19T09:35:19Z 2018-06-19T09:35:19Z 2007 SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population / X.Q. Wang, X. Miao, Q. Cai, M.M. Garcia-Barcelo, S.T. Fan // Experimental Oncology. — 2007. — Т. 29, № 1. — С. 71-73. — Бібліогр.: 7 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138565 A variable number of tandem repeats (VNTR) polymorphism in regulatory region of SMYD3 coding for histone methyltransferase has been shown to be associated with colorectal cancer, hepatocellular carcinoma (HCC), and breast cancer in Japanese population. Aim of the study is to investigate the potential association between the functional SMYD3 tandem repeats polymorphism and HCC in Chinese population. Material and Methods: The case-control study included 200 HCC patients and 261 healthy controls. The VNTR polymorphism in the promoter of SMDY3 was genotyped by PCR and direct-sequencing analysis. Odds ratio and 95% confidence interval were used to estimate the association between the polymorphisms and risk of HCC. Results: The allele frequencies for SMYD3 2 and 3 repeats were 15.71% and 84.29% among controls; and 12.75%, and 87.25% among cases (P = 0.22). The odds ratio for 3/3 versus 2/2 and 2/3 genotypes was 1.30 (P = 0.18). The frequencies of 3 alleles were not increased with HCC stage increased (trend test, P = 0.45). Conclusion: SMYD3 polymorphism is not associated with the occurrence and metastasis of HCC in Chinese population. Известно, что полиморфизм тандемных повторов (VNTR) в регуляторном участке гена SMYD3,кодирующем метилтрансферазу гистонов, ассоциирован с развитием рака прямой кишки, карциномы печени (HCC) и рака молочной железы и является популяционно-зависимой характеристикой. Цель работы состояла в исследовании возможной связи междуVNTR Геном SMYD3 и развитием HCC у населения Китая. Материалы и методы: исследование типа “случай-контроль” проводили с участием 200 пациентов с HCC и 261 здорового донора. Полиморфизм VNTR в промоторной области гена SMDY3генотипировали методами PCR. Для оценки связи между полиморфизмом и риском развитияHCC использовали отношение шансов (OR) и 95% доверительные интервалы. Результаты: частота аллелей для повторов SMYD3 2 и 3 составила 15,71 и 84,29% в контрольной группе и 12,75 и 87,25% — в группе больных (P = 0,22). OR Генотипов 3/3 versus 2/2 и 2/3 составило 1,30 (P = 0.18). Частота 3 аллелей не возрастала при повышении стадии заболевания (P = 0,45). Выводы: полиморфизм гена SMYD3 не ассоциирован с развитием и метастазированием HCC у населения Китая. This study was supported by Sun C.Y. Research Foundation for Hepatobiliary and Pancreatic Surgery of the University of Hong Kong. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Short communications SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population Отсутствие связи между полиморфизмом тандемных повторов SMYD3 и возникновением и метастазированием карциномы печени у населения Китая Article published earlier |
| spellingShingle | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population Wang, X.Q. Miao, X. Cai, Q. Garcia-Barcelo, M.M. Fan, S.T. Short communications |
| title | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population |
| title_alt | Отсутствие связи между полиморфизмом тандемных повторов SMYD3 и возникновением и метастазированием карциномы печени у населения Китая |
| title_full | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population |
| title_fullStr | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population |
| title_full_unstemmed | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population |
| title_short | SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population |
| title_sort | smyd3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a chinese population |
| topic | Short communications |
| topic_facet | Short communications |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/138565 |
| work_keys_str_mv | AT wangxq smyd3tandemrepeatspolymorphismisnotassociatedwiththeoccurrenceandmetastasisofhepatocellularcarcinomainachinesepopulation AT miaox smyd3tandemrepeatspolymorphismisnotassociatedwiththeoccurrenceandmetastasisofhepatocellularcarcinomainachinesepopulation AT caiq smyd3tandemrepeatspolymorphismisnotassociatedwiththeoccurrenceandmetastasisofhepatocellularcarcinomainachinesepopulation AT garciabarcelomm smyd3tandemrepeatspolymorphismisnotassociatedwiththeoccurrenceandmetastasisofhepatocellularcarcinomainachinesepopulation AT fanst smyd3tandemrepeatspolymorphismisnotassociatedwiththeoccurrenceandmetastasisofhepatocellularcarcinomainachinesepopulation AT wangxq otsutstviesvâzimeždupolimorfizmomtandemnyhpovtorovsmyd3ivozniknoveniemimetastazirovaniemkarcinomypečeniunaseleniâkitaâ AT miaox otsutstviesvâzimeždupolimorfizmomtandemnyhpovtorovsmyd3ivozniknoveniemimetastazirovaniemkarcinomypečeniunaseleniâkitaâ AT caiq otsutstviesvâzimeždupolimorfizmomtandemnyhpovtorovsmyd3ivozniknoveniemimetastazirovaniemkarcinomypečeniunaseleniâkitaâ AT garciabarcelomm otsutstviesvâzimeždupolimorfizmomtandemnyhpovtorovsmyd3ivozniknoveniemimetastazirovaniemkarcinomypečeniunaseleniâkitaâ AT fanst otsutstviesvâzimeždupolimorfizmomtandemnyhpovtorovsmyd3ivozniknoveniemimetastazirovaniemkarcinomypečeniunaseleniâkitaâ |