维吾尔族、汉族散发性乳腺癌BRCA1基因rs16941及rs16942位点多态性分析
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摘要
目的探讨维吾尔族及汉族散发性乳腺癌BRCA1基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)是否存在差异,并分析SNPs位点与肿瘤易感性的关系。方法选取100例散发性乳腺癌(维吾尔族、汉族各50例)及100例乳腺腺病(维吾尔族、汉族各50例)作为分析对象,对BRCA1基因rs16941及rs16942进行DNA测序。结果 rs16941及rs16942的AA、AG、GG基因型在维吾尔族、汉族乳腺癌组之间的分布差异有统计学意义(P=0.009,P=0.017)。肿瘤易感性比较:维吾尔族rs16941位点中AG与AA基因型相比,其能够降低乳腺癌的发病风险(OR=0.964,95%CI:0.260~3.583,P=0.009);维吾尔族rs16942位点中AG与AA基因型相比,其能够增加乳腺癌的发病风险(OR=1.017,95%CI:0.293~3.916,P=0.017)。汉族rs16941位点中AG与AA基因型相比,其能够降低乳腺癌的发病风险(OR=0.824,95%CI:0.210~3.234,P=0.044)。结论 rs16941及rs16942的AA、AG、GG基因型在维吾尔族、汉族乳腺癌组的分布,差异有统计学意义;SNPs与肿瘤易感性有相关性。
Purpose To investigate whether there is a difference in BRCA1 gene single nucleotide polymorphisms(SNPs) in Uighurs and Han Chinese sporadic breast cancer,and to analyze the relationship between SNPs locus and tumor susceptibility.Methods 100 cases of sporadic breast cancer(Uighur and Han 50 cases each) and 100 cases of mammary gland disease(Uighur and Han 50 cases each) were collected as the research object,the BRCA1 gene rsl6941 and rsl6942 were sequenced.Results The distribution of AA,AG and GG genotypes of rsl6941 and rsl6942 between Uygur and Han breast cancer groups were statistically significant(P = 0.009,P =0.017).Compared with AA genotype of rs 16941,AG genotype of rs 16941 could reduce the risk of breast cancer in Uighurs(OR= 0.964,95%CI:0.260-3.583,P = 0.009).Compared with AA genotype of rsl6942,AG genotype of rsl6942 could increase the risk of breast cancer in Uighurs(OR = 1.017,95%CI:0.293-3.916,P= 0.017).Compared with AA genotype of rs 16941,AG genotype could reduce the risk of breast cancer in Han nationality(OR = 0.824,95%CI:0.210-3.234,P =0.044).Conclusion The distribution of AA,AG and GG genotypes of rs16941 and rs16942 in Uygur and Han breast cancer groups are statistically significant,and SNPs is correlated with tumor susceptibility.
Purpose To investigate whether there is a difference in BRCA1 gene single nucleotide polymorphisms(SNPs) in Uighurs and Han Chinese sporadic breast cancer,and to analyze the relationship between SNPs locus and tumor susceptibility.Methods 100 cases of sporadic breast cancer(Uighur and Han 50 cases each) and 100 cases of mammary gland disease(Uighur and Han 50 cases each) were collected as the research object,the BRCA1 gene rsl6941 and rsl6942 were sequenced.Results The distribution of AA,AG and GG genotypes of rsl6941 and rsl6942 between Uygur and Han breast cancer groups were statistically significant(P = 0.009,P =0.017).Compared with AA genotype of rs 16941,AG genotype of rs 16941 could reduce the risk of breast cancer in Uighurs(OR= 0.964,95%CI:0.260-3.583,P = 0.009).Compared with AA genotype of rsl6942,AG genotype of rsl6942 could increase the risk of breast cancer in Uighurs(OR = 1.017,95%CI:0.293-3.916,P= 0.017).Compared with AA genotype of rs 16941,AG genotype could reduce the risk of breast cancer in Han nationality(OR = 0.824,95%CI:0.210-3.234,P =0.044).Conclusion The distribution of AA,AG and GG genotypes of rs16941 and rs16942 in Uygur and Han breast cancer groups are statistically significant,and SNPs is correlated with tumor susceptibility.
引文
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[19]Cox D G,Kraft P,Hankinson S E,et al.Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer[J].Breast Cancer Res,2005,7(2);171-175.
[2]Chen L,Liang Y,Qiu J,et al.Significance of rsl271572 in the estrogen receptor beta gene promoter and its correlation with breast cancer in asouthwestern Chinese population[J].J Biomed Sci,2013,20(1):32.
[3]Cao W,Wang X,Li J C,et al.Hereditary breast cancer in the Han Chinese Population[J].J Epidemiol,2013,23(2):75-84.
[4]Ripperger T,Gadzicki D,Meindl A,et al.Breast cancer susceptibility:current knowledge and implications for genetic counselling[J].Eur J Hum Genet,2009,17(6):722-731.
[5]Simon K,Geigl J B,Pristauz G,et al.Genes beyond BRCA1 and BRCA2 for hereditary breast cancer[J].Wien Med Wochenschr,2010,160(19-20):478-482.
[6]Lin W Y,Brock I W,Connley D,et al.Associations of ATR and CHEK1 single nucleotide polymorphisms with breast cancer[J].PLoS One,2013,8(7):e68578.
[7]Yang Z,Fang X,Pei X,et al.Polymorphisms in the ERCC1 and XPF genes and risk of breast cancer in a Chinese population[J].Genet Test Mol Biomarkere,2013,17(9):700-706.
[8]Chang W C,Fang Y Y,Chang H W,et al.Identifying association model for single-nucleotide polymorphisms of ORAI1 gene for breast cancer[J].Cancer Cell Int,2014,14(1):29.
[9]Frazer K A,Ballinger D G,Cox D R,et al.A second generation human haplotype map of over 3.1 million SNPs[J].Nature,2007,449(7164):851-861.
[10]Ding H,Jin X,Ding N,et al.Single nucleotide polymorphisms of CD20 gene and their relationship with clinical efficacy of R-CHOP in patientswith diffuse large B cell lymphoma[J].Cancer Cell Int,2013,13:58.
[11]Cox D G,Simard J,Sinnett D,et al.Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1mutation carriers[J].Hum Mol Genet,2011,20(23):4732-4747.
[12]罗丹,袁军.易感基因和单核苷酸多态性与乳腺癌关系的研究进展[J].国际检验医学杂志,2012,33(7):823-830.
[13]康毓芝,杨宝珍,陈耀平,等.宁夏地区回族女性散发性乳腺癌易感基因BRCA1/BRCA2突变的研究[J].临床检验杂志,2011,29(4):295-297.
[14]Kuusisto K M,Bebel A,Vihinen M,et al.Screening for BRCA1,BRCA2,CHEK2,PALB2,BR1P1,RAD50,and CDH1 mutations in high-risk finnish BRCA1/2-founder mutation-negative breast and/or ovarian cancer individuals[J].Breast Cancer Res,2011,13(1):R20.
[15]Celebiler C A,Kilic Y,Saydam S,et al.Predicting invasive phenotype with CDH1,CDH13,CD44,and TIMP3 gene expression in primary breast cancer[J].Cancer Sci,2009,100(12):2341-2345.
[16]Rosen E M,Fan S,Pestell R G,et al.BRCA1 in hormone-responsive cancers[J].Trends Endocrinol Metab,2003,14(8):378-385.
[17]Zhang J,Fackenthal J D,Huo D,et al.Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population[J].Breast Cancer Res Treat,2010,124(2):573-577.
[18]饶南燕.邵志敏.中国汉族乳腺癌人群BRCA基因的研究[D].上海:复旦大学博士学位论文,2008:1-120.
[19]Cox D G,Kraft P,Hankinson S E,et al.Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer[J].Breast Cancer Res,2005,7(2);171-175.