Bcl-2基因多态性与青海地区回族乳腺癌患者临床生物学指标关系的研究
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摘要
目的:探讨B细胞淋巴瘤/白血病-2(Bcl-2)基因C(-938)A多态性,与青海地区回族乳腺癌患者临床生物学指标的关系。方法:采用聚合酶链反应-限制性酶切片段长度多态性分析(PCR-RFLP)检测2014年1月—2017年11月青海大学附属医院肿瘤外二科符合纳入及排除标准的90例回族乳腺癌患者的Bcl-2基因C(-938)A(AA、AC、CC基因型)的多态性,研究基因型频率的分布情况及与临床生物学指标[肿瘤的直径、临床分期、病理类型、免疫组化指标(ER、PR、Her-2)、腋淋巴结转移数目、分子分型及组织学分级]的关系。结果:在进行研究的90例标本中,由于野生型AA例数较少,无法进行独立分析,故将AA与CC基因型合并分析。得出结果为CA型与AA+CC型在临床生物学指标:肿瘤的直径、临床分期、病理类型、免疫组化指标(ER、PR、Her-2、腋淋巴结转移数目、分子分型及组织学分级中的分布差异均无统计学意义(P>0.05)。结论:Bcl-2基因C(-938)A多态性与青海地区回族乳腺癌患者临床生物学指标无相关性。
Objective:This study is to explore the relationship between the B cell lymphoma/leukemia-2(bcl-2)gene C(-938)A polymorphism and the clinical biological indicators of hui breast cancer patients in Qinghai.Methods:The polymorphism of bcl-2 gene C(-938)A(AA、AC、CC genotype)of 90 hui patients with breast cancer,who were enrolled and excluded in the department of Breast Thyroid Surgery in the Affiliated Hospital of Qinghai university,was detected by the method of polymerase chain of reaction-restriction enzyme fragment length polymorphism(PCR-RFLP),studying the distribution of genotype frequency and clinical biological indicator(the diameter of the tumor,clinical stage,pathological type,immunohistochemical index ER,PR,and Her-2,the number of axillary lymph node metastasis,molecular classification and histological grading).Results:In the 90 samples of the study,the AA and CC genotypes were analyzed together due to the small number of wild-type AA cases which could not be independently analyzed.The results showed that there was no significant difference in the distribution of CA and AA+CC(P>0.05)in clinical biological indicators(tumor diameter,clinical stage,pathological type,immunohistochemical index ER、PR,and Her-2,axillary lymph node metastasis,molecular typing and histological classification).Conclusion:bcl-2 gene C(-938)A polymorphism has no correlation with the clinical biological indicators of patients with breast cancer in Qinghai.
Objective:This study is to explore the relationship between the B cell lymphoma/leukemia-2(bcl-2)gene C(-938)A polymorphism and the clinical biological indicators of hui breast cancer patients in Qinghai.Methods:The polymorphism of bcl-2 gene C(-938)A(AA、AC、CC genotype)of 90 hui patients with breast cancer,who were enrolled and excluded in the department of Breast Thyroid Surgery in the Affiliated Hospital of Qinghai university,was detected by the method of polymerase chain of reaction-restriction enzyme fragment length polymorphism(PCR-RFLP),studying the distribution of genotype frequency and clinical biological indicator(the diameter of the tumor,clinical stage,pathological type,immunohistochemical index ER,PR,and Her-2,the number of axillary lymph node metastasis,molecular classification and histological grading).Results:In the 90 samples of the study,the AA and CC genotypes were analyzed together due to the small number of wild-type AA cases which could not be independently analyzed.The results showed that there was no significant difference in the distribution of CA and AA+CC(P>0.05)in clinical biological indicators(tumor diameter,clinical stage,pathological type,immunohistochemical index ER、PR,and Her-2,axillary lymph node metastasis,molecular typing and histological classification).Conclusion:bcl-2 gene C(-938)A polymorphism has no correlation with the clinical biological indicators of patients with breast cancer in Qinghai.
引文
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2 吴在德,吴肇汉.外科学.第7版.北京:人民卫生出版社,2012,308~309.
3 Mavaddat N,Antoniou AC,Easton DF,et al.Genetic susceptibility to breast cancer.Molecular Oncology,2010,4(3):174~191.
4 Hengartner MO.The biochemistry of apoptosis.Nature,2000,407(6 805):770~776.
5 Campling BG,Pym J,Baker HM,et al.Chemosensitivity test of small cell lung cnacer using the MTT assay.Br J Cancer,1991,63(1):75~83.
6 王本忠,朱新生.改良MTT法检测胃癌乳腺癌体外药物敏感性.临床外科杂志,1998,6(5):258~260.
7 Tsujimoto Y,Gorham J,Cossman J,et al.Croce CM:The t(14;18)chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining.Science,1985,229(4 720):1 390~1 393.
8 Seto M,Jaeger U,Hockett RD,et al.Alternative promoters and exons,somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma.EMBO J,1988,7(1):123~131.
9 Young RL,Korsmeyer SJ.A negative regulatory element in the Bcl-2 5’-untranslated region inhibits expression from an upstream promoter.Mol Cell Biol,1993,13(6):3 686~3 697.
10 Bachmann HS,Otterbach F,Callies R,et al.The AA genotype of the regulatory BCL2 promoter polymorphism(938C>A)is associated with a favorable outcome in lymph node negative invasive breast cancer patients.Clin Cancer Res,2007,13(19):5 790~5 797.
11 王晓武.Bcl-2和Bax基因及多态性与乳腺癌关系的研究进展.青海医药杂志,2013,43(2):78~79.
12 Sobin LH GM,Wittekind C.TNM classification of Malignant Tumours(7th Edition).American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).Oxford,UK:Wiley-Blackwell,2009,345~376.
13 Meyer JS,Alvarez C,Milikowski C,et al.Breast carcinoma malignancy grading By Bloom-Richardson system vs proliferation index:reproducibility of grade and Advantages of proliferation index.Mod pathol,2005,13(2):39~48.
14 Korsmeyer SJ.Bcl-2initiates a new category of oncogenes:regu-lator of cell.Blood,1992,80:879.
15 Park BL,Kim LH,Cheong HS,et al.Identification of variants in cyclin D1(CCND1)and B-Cell CLL/lymphoma 2(BCL2).Hum Genet,2004,49(8):449~454.
16 Ihemelandu CU,Leffall LD Jr,Dewitty RL,et al.Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women:age-specific prevalence and survival.J Suig Res,2007,143(1):109 ~118.
17 Nuckel H,Frey UH,Bau M,et al.Association of a novel regulatory polymorphism(-938C>A)in the BCL2gene promoter with disease progression and survival in chronic lymphocytic leukemia.Blood,2007,109(1):290~297.
18 N Zhang,X Li,K Tao,et al.BCL-2(-938C>A)polymorphism is associated with breast cancer susceptibility.BMC Medical Genetics,2011,12:48.
19 Carey LA,Dees EC,Sawyer L,et al.The triple negative paradox:Primary tumor chemosensitivity of breast cancer subtypes.Clin Cancer Res,2007,13(8):2 329~2 334.
20 吴炅,沈镇宙,邵志敏.乳腺癌细胞凋亡及相关基因表达的预后研究.上海医学,1999,22(1):27~31.
21 Rossi D,Rasi S,Capello D,et al.Prognostic assessment of Bcl-2-938C>A polymorphism in chronic lymphocytic leukemia.Blood,2008,111(1):466~468.
22 Zenz T,Benner A,Duhrsen U,et al.Bcl-2-938C>A polymorphism and disease progression in chronic lymphocytic leukemia.Leuk Lymphoma,2009,50(11):1 837~1 842.
23 白杨,戴殿禄,马国明,等.Bcl-2基因多态性与乳腺癌临床生物学指标的关系.肿瘤,2010,30(1):48~52.
24 杨勇莉,王晓武,王玉花,等.青海地区乳腺癌患者B淋巴细胞瘤-2基因C(-938)A多态性与临床生物学指标关系研究.中国全科医学,2017,20(33):4 151~4 155.
2 吴在德,吴肇汉.外科学.第7版.北京:人民卫生出版社,2012,308~309.
3 Mavaddat N,Antoniou AC,Easton DF,et al.Genetic susceptibility to breast cancer.Molecular Oncology,2010,4(3):174~191.
4 Hengartner MO.The biochemistry of apoptosis.Nature,2000,407(6 805):770~776.
5 Campling BG,Pym J,Baker HM,et al.Chemosensitivity test of small cell lung cnacer using the MTT assay.Br J Cancer,1991,63(1):75~83.
6 王本忠,朱新生.改良MTT法检测胃癌乳腺癌体外药物敏感性.临床外科杂志,1998,6(5):258~260.
7 Tsujimoto Y,Gorham J,Cossman J,et al.Croce CM:The t(14;18)chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining.Science,1985,229(4 720):1 390~1 393.
8 Seto M,Jaeger U,Hockett RD,et al.Alternative promoters and exons,somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma.EMBO J,1988,7(1):123~131.
9 Young RL,Korsmeyer SJ.A negative regulatory element in the Bcl-2 5’-untranslated region inhibits expression from an upstream promoter.Mol Cell Biol,1993,13(6):3 686~3 697.
10 Bachmann HS,Otterbach F,Callies R,et al.The AA genotype of the regulatory BCL2 promoter polymorphism(938C>A)is associated with a favorable outcome in lymph node negative invasive breast cancer patients.Clin Cancer Res,2007,13(19):5 790~5 797.
11 王晓武.Bcl-2和Bax基因及多态性与乳腺癌关系的研究进展.青海医药杂志,2013,43(2):78~79.
12 Sobin LH GM,Wittekind C.TNM classification of Malignant Tumours(7th Edition).American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).Oxford,UK:Wiley-Blackwell,2009,345~376.
13 Meyer JS,Alvarez C,Milikowski C,et al.Breast carcinoma malignancy grading By Bloom-Richardson system vs proliferation index:reproducibility of grade and Advantages of proliferation index.Mod pathol,2005,13(2):39~48.
14 Korsmeyer SJ.Bcl-2initiates a new category of oncogenes:regu-lator of cell.Blood,1992,80:879.
15 Park BL,Kim LH,Cheong HS,et al.Identification of variants in cyclin D1(CCND1)and B-Cell CLL/lymphoma 2(BCL2).Hum Genet,2004,49(8):449~454.
16 Ihemelandu CU,Leffall LD Jr,Dewitty RL,et al.Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women:age-specific prevalence and survival.J Suig Res,2007,143(1):109 ~118.
17 Nuckel H,Frey UH,Bau M,et al.Association of a novel regulatory polymorphism(-938C>A)in the BCL2gene promoter with disease progression and survival in chronic lymphocytic leukemia.Blood,2007,109(1):290~297.
18 N Zhang,X Li,K Tao,et al.BCL-2(-938C>A)polymorphism is associated with breast cancer susceptibility.BMC Medical Genetics,2011,12:48.
19 Carey LA,Dees EC,Sawyer L,et al.The triple negative paradox:Primary tumor chemosensitivity of breast cancer subtypes.Clin Cancer Res,2007,13(8):2 329~2 334.
20 吴炅,沈镇宙,邵志敏.乳腺癌细胞凋亡及相关基因表达的预后研究.上海医学,1999,22(1):27~31.
21 Rossi D,Rasi S,Capello D,et al.Prognostic assessment of Bcl-2-938C>A polymorphism in chronic lymphocytic leukemia.Blood,2008,111(1):466~468.
22 Zenz T,Benner A,Duhrsen U,et al.Bcl-2-938C>A polymorphism and disease progression in chronic lymphocytic leukemia.Leuk Lymphoma,2009,50(11):1 837~1 842.
23 白杨,戴殿禄,马国明,等.Bcl-2基因多态性与乳腺癌临床生物学指标的关系.肿瘤,2010,30(1):48~52.
24 杨勇莉,王晓武,王玉花,等.青海地区乳腺癌患者B淋巴细胞瘤-2基因C(-938)A多态性与临床生物学指标关系研究.中国全科医学,2017,20(33):4 151~4 155.