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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (5): 822-828. doi: 10.19723/j.issn.1671-167X.2022.05.007

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基因多态性对中国汉族女性乳腺癌遗传易感性的影响

方伟岗1,*(),田新霞1,2,解云涛3   

  1. 1 北京大学基础医学院病理学系，北京 100191
    2 北京大学第三医院病理科，北京 100191
    3 北京大学肿瘤医院家族遗传性肿瘤中心，北京 100142
  • 收稿日期:2022-06-25 出版日期:2022-10-18 发布日期:2022-10-14
  • 通讯作者: 方伟岗 E-mail:wgfang@bjmu.edu.cn
  • 作者简介:方伟岗，病理学博士，教授，博士生导师，北京大学临床研究所所长。历任中华医学会病理学分会常务委员、国际病理学会中国分部主席、吴阶平医学基金会病理学部副主任委员、中国研究型医院学会移动医疗专业委员会主任委员、中国抗癌协会肿瘤转移专业委员会主任委员、中华医学会医学科研管理学分会主任委员、中华医学科技奖评审委员会委员、华夏医学科技奖理事会常务理事、教育部科学技术委员会第五届学部委员等，并担任多个国内外期刊的副主编或编委，受聘澳大利亚Monash大学客座教授。主持国家重点研发计划、国家重点基础研究发展计划(973计划)课题、国家自然科学基金等30余项国家/省部级研究课题。研究成果以第一或责任作者在国内外杂志发表论文80余篇(其中SCI论文30余篇)，获得教育部“跨世纪优秀人才”“北京青年五四奖章”“卫生部有突出贡献中青年专家”等荣誉，享受国务院特殊津贴。
    从事肿瘤转移机制研究30余年，在国际上首次发现ATP能够抑制激素非依赖型人前列腺癌细胞的体外生长，发现ATP对肿瘤细胞的作用具有多样性，首次提出肿瘤微环境中ATP是重要促侵袭因子的假说并予以证实，为肿瘤侵袭发生的机制及调控提供了新的依据。运用单核苷酸多态性及单体型相关性分析对较大样本量中国汉族妇女中某些热点基因的遗传学多态性与乳腺癌易感性、肿瘤演进及生存的关系进行了研究，为相关领域的研究提供了有益的数据
  • 基金资助:
    国家自然科学基金(81872382);国家自然科学基金(81672790);国家自然科学基金(81171961)

伟岗 方1,*(),新霞 田1,2,云涛 解3   

  • Received:2022-06-25 Online:2022-10-18 Published:2022-10-14
  • Contact: 伟岗 方 E-mail:wgfang@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(81872382);the National Natural Science Foundation of China(81672790);the National Natural Science Foundation of China(81171961)

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关键词: 乳腺癌, 基因多态性, 中国汉族女性

中图分类号: 

  • R34

图1

功能性SNP可以影响该基因编码蛋白的结构或表达水平 红色“∣”，SNP位点。"

表1

基因多态性与乳腺癌遗传易感性的相关性分析结果"

基因名称 SNP位点 与乳腺癌易感性明显相关联的位点 参考文献
BRCA1 rs8176323, rs8176303, rs8176199, rs3737559, rs8067269, rs2070833 rs3737559(C>T)的TT/TC基因型携带者与CC基因型相比，发生乳腺癌风险增加35% [9]
AURKA rs6064391, rs911162, rs2298016, rs8117896, rs10485805, rs6024836, rs2273535, rs2064863 rs6024836(A>G)的GG基因型携带者与AG/AA基因型相比，发生乳腺癌的风险提高54%; rs2273535(T>A)的AA/TA基因型携带者与TT基因型相比，发生乳腺癌风险增加81% [9]
CENTROBIN rs4239115, rs4791987, rs11078719, rs11650083, rs4462665 rs11650083(A>C)的AC、CC基因型携带者与AA基因型相比，发生乳腺癌的风险分别降低19%、27%; CATCG [rs4239115 (C>T)+rs4791987(A>G)+rs11078719 (T>C)+rs11650083(A>C)+rs4462665(G>C)]单体型携带者与最常见单体型CATAG相比，发生乳腺癌的风险降低86% [10]
CDK1 rs2448343, rs3213048, rs3213067, rs1871446, rs10711, rs1060373 rs2448343(G>A)的AA/AG基因型携带者与GG基因型相比，发生乳腺癌风险降低19%; 对于体重指数 < 23 kg/m2的女性，rs2448343(G>A)的AA/AG基因型携带者与GG基因型相比，发生乳腺癌风险降低42%; rs1871446(C>T)的TT基因型携带者与CT/CC基因型相比，发生乳腺癌的风险降低64% [11]
TGFB1 rs1800469, rs2241716, rs4803455, rs747857, rs12983047, rs10417924, rs12981053 rs1800469(C>T)的TT/TC基因型携带者与CC基因型相比，发生乳腺癌风险降低24%; rs10417924(C>T)的TT/TC基因型携带者与CC基因型相比，发生乳腺癌的风险增加27% [12]
CDH1 rs7200690, rs12185157, rs7198799, rs17715799, rs10431923, rs7186053, rs6499199, rs4783689, rs13689 rs13689(T>C)的CC基因型携带者与CT/TT基因型相比，发生乳腺癌的风险提高89% [13]
PAI-1 rs2227631, rs6090, rs2227667, rs2227672, rs2227692, rs11178 rs2227672(G>T)的TT基因型携带者与GG/GT基因型相比，发生乳腺癌的风险提高1.52倍 [14]
NTN4 rs10859915, rs17356907, rs11836367, rs61938093, rs11836367(C>T)的CT/TT基因型携带者与CC基因型相比，发生乳腺癌风险降低27%; rs61938093(C>T)的CT/TT基因型携带者与CC基因型相比，发生乳腺癌风险降低23%;rs17356907(A>G)的AG/GG基因型携带者与AA基因型相比，发生乳腺癌风险降低22% [15]
1 Britt KL , Cuzick J , Phillips KA . Key steps for effective breast cancer prevention[J]. Nat Rev Cancer, 2020, 20 (8): 417- 436.
doi: 10.1038/s41568-020-0266-x
2 Fanfani V , Zatopkova M , Harris AL , et al. Dissecting the heritable risk of breast cancer: from statistical methods to susceptibility genes[J]. Semin Cancer Biol, 2021, 72, 175- 184.
doi: 10.1016/j.semcancer.2020.06.001
3 Lilyquist J , Ruddy KJ , Vachon CM , et al. Common genetic variation and breast cancer risk: past, present, and future[J]. Cancer Epidemiol Biomarkers Prev, 2018, 27 (4): 380- 394.
doi: 10.1158/1055-9965.EPI-17-1144
4 Marian AJ . Molecular genetic studies of complex phenotypes[J]. Transl Res, 2012, 159 (2): 64- 79.
doi: 10.1016/j.trsl.2011.08.001
5 Genomes-Project C , Abecasis GR , Auton A , et al. An integrated map of genetic variation from 1, 092 human genomes[J]. Nature, 2012, 491 (7422): 56- 65.
doi: 10.1038/nature11632
6 Gabriel SB , Schaffner SF , Nguyen H , et al. The structure of haplotype blocks in the human genome[J]. Science, 2002, 296 (5576): 2225- 2229.
doi: 10.1126/science.1069424
7 Daly MJ , Rioux JD , Schaffner SF , et al. High-resolution haplotype structure in the human genome[J]. Nat Genet, 2001, 29 (2): 229- 232.
doi: 10.1038/ng1001-229
8 Stadler ZK , Thom P , Robson ME , et al. Genome-wide association studies of cancer[J]. J Clin Oncol, 2010, 28 (27): 4255- 4267.
doi: 10.1200/JCO.2009.25.7816
9 Ruan Y , Song AP , Wang H , et al. Genetic polymorphisms in Aurora-A and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population[J]. J Pathol, 2011, 225 (4): 535- 543.
doi: 10.1002/path.2902
10 Wang H , Xie YT , Han JY , et al. Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population[J]. Breast Cancer Res Treat, 2012, 136 (1): 241- 251.
doi: 10.1007/s10549-012-2244-9
11 Han JY , Wang H , Xie YT , et al. An association study of germline polymorphisms in CCNE1 and CDK2 with breast cancer risk, tumor characteristics and survival in a Chinese Han population[J]. PLoS One, 2012, 7 (11): e49296.
doi: 10.1371/journal.pone.0049296
12 Zhou YT , Zheng LY , Wang YJ , et al. Effect of functional variant rs11466313 on breast cancer susceptibility and TGFB1 promoter activity[J]. Breast Cancer Res Treat, 2020, 184 (1): 237- 248.
doi: 10.1007/s10549-020-05841-w
13 Li Y , Chen YL , Xie YT , et al. Association study of germline variants in CCNB1 and CDK1 with breast cancer susceptibility, progression and survival among Chinese Han women[J]. PLoS One, 2013, 8 (12): e84489.
doi: 10.1371/journal.pone.0084489
14 陈奕霖, 贾玉棉, 解云涛, 等. PAI-1基因单核苷酸多态性与乳腺癌易感性及预后的关联分析[J]. 中华病理学杂志, 2016, 45 (8): 533- 539.
doi: 10.3760/cma.j.issn.0529-5807.2016.08.008
15 Yang H , Ting X , Geng YH , et al. A risk variant rs11836367 contributes to breast cancer onset and metastasis by attenuating Wnt signaling via regulating NTN4 expression[J]. Sci Advs, 2022, 8 (23): eabn3509.
doi: 10.1126/sciadv.abn3509
16 Baynes C , Healey CS , Pooley KA , et al. Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk[J]. Breast Cancer Res, 2007, 9 (2): R27.
doi: 10.1186/bcr1669
17 Bonnen PE , Wang PJ , Kimmel M , et al. Haplotype and linkage disequilibrium architecture for human cancer-associated genes[J]. Genome Res, 2002, 12 (12): 1846- 1853.
doi: 10.1101/gr.483802
18 Naso FD , Boi D , Ascanelli C , et al. Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer[J]. Oncogene, 2021, 40 (23): 3917- 3928.
doi: 10.1038/s41388-021-01766-w
19 Sun T , Miao X , Wang J , et al. Functional Phe31Ile polymorphism in Aurora A and risk of breast carcinoma[J]. Carcinogenesis, 2004, 25 (11): 2225- 2230.
doi: 10.1093/carcin/bgh244
20 Lo YL , Yu JC , Chen ST , et al. Breast cancer risk associated with genotypic polymorphism of the mitosis-regulating gene Aurora-A/STK15/BTAK[J]. Int J Cancer, 2005, 115 (2): 276- 283.
doi: 10.1002/ijc.20855
21 Zou C , Li J , Bai Y , et al. Centrobin: a novel daughter centriole-associated protein that is required for centriole duplication[J]. J Cell Biol, 2005, 171 (3): 437- 445.
doi: 10.1083/jcb.200506185
22 Olson JE , Wang X , Pankratz VS , et al. Centrosome-related genes, genetic variation, and risk of breast cancer[J]. Breast Cancer Res Treat, 2011, 125 (1): 221- 228.
doi: 10.1007/s10549-010-0950-8
23 Jeong Y , Lee J , Kim K , et al. Characterization of NIP2/centrobin, a novel substrate of Nek2, and its potential role in microtubule stabilization[J]. J Cell Sci, 2007, 120 (12): 2106- 2116.
doi: 10.1242/jcs.03458
24 Quan L , Gong Z , Yao S , et al. Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry[J]. Int J Cancer, 2014, 134 (6): 1408- 1421.
doi: 10.1002/ijc.28458
25 Cox DG , Penney K , Guo Q , et al. TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses' Health Study[J]. BMC Cancer, 2007, 7, 175.
doi: 10.1186/1471-2407-7-175
26 Healy J , Dionne J , Bélanger H , et al. Functional impact of sequence variation in the promoter region of TGFB1[J]. Int J Cancer, 2009, 125 (6): 1483- 1489.
doi: 10.1002/ijc.24526
27 Michailidou K , Hall P , Gonzalez-Neira A , et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk[J]. Nat Genet, 2013, 45 (4): 353- 361.
doi: 10.1038/ng.2563
28 Maurano MT , Humbert R , Rynes E , et al. Systematic localization of common disease-associated variation in regulatory DNA[J]. Science, 2012, 337 (6099): 1190- 1195.
doi: 10.1126/science.1222794
29 Milne RL , Kuchenbaecker KB , Michailidou K , et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer[J]. Nat Genet, 2017, 49 (12): 1767- 1778.
doi: 10.1038/ng.3785
30 Zheng W , Zhang B , Cai Q , et al. Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls[J]. Hum Mol Genet, 2013, 22 (12): 2539- 2550.
doi: 10.1093/hmg/ddt089
31 Ferreira MA , Gamazon ER , Al-Ejeh F , et al. Genome-wide association and transcriptome studies identify target genes and risk loci for breast can-cer[J]. Nat Commun, 2019, 10 (1): 1741.
doi: 10.1038/s41467-018-08053-5
32 Rivandi M , Martens JWM , Hollestelle A . Elucidating the underlying functional mechanisms of breast cancer susceptibility through post-gwas analyses[J]. Front Genet, 2018, 9, 1- 18.
doi: 10.3389/fgene.2018.00001
33 Ghoussaini M , Edwards SL , Michailidou K , et al. Evidence that breast cancer risk at the 2q35 locus is mediated through igfbp5 regulation[J]. Nat Commun, 2014, 5, 4999.
doi: 10.1038/ncomms5999
34 Quigley DA , Fiorito E , Nord S , et al. The 5p12 breast cancer susceptibility locus affects mrps30 expression in estrogen-receptor positive tumors[J]. Mol Oncol, 2014, 8 (2): 273- 284.
doi: 10.1016/j.molonc.2013.11.008
35 Lawrenson K , Kar S , Mccue K , et al. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus[J]. Nat Commun, 2016, 7, 12675.
doi: 10.1038/ncomms12675
36 Wen W , Shu XO , Guo X , et al. Prediction of breast cancer risk based on common genetic variants in women of east Asian ancestry[J]. Breast Cancer Res, 2016, 18 (1): 1- 8.
doi: 10.1186/s13058-015-0660-6
37 Mavaddat N , Michailidou K , Dennis J , et al. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes[J]. Am J Hum Genet, 2019, 104 (1): 21- 34.
doi: 10.1016/j.ajhg.2018.11.002
38 Diet GS , Macinnis RJ , Bickerstaffe A , et al. Breast cancer risk prediction using clinical models and 77 independent risk-associated snps for women aged under 50 years: Australian breast cancer family registry[J]. Cancer Epidemiol Biomarkers Prev, 2016, 25 (2): 359- 365.
doi: 10.1158/1055-9965.EPI-15-0838
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