湖北地区人群乳腺癌易感基因FGFR2多态性研究
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摘要
目的:探讨湖北地区人群成纤维细胞生长因子受体-2基因(FGFR2)第2内含子单核苷酸多态性(SNP)与乳腺癌易感性的关系。方法:采用PCR及DNA测序方法,对汉族204例女性乳腺癌患者(乳腺癌组)和192名正常女性(对照组)FGFR2基因第2内含子区的2个多态性位点(rs2981582和rs10510097)进行分析,计算基因型和等位基因频率。结果:汉族人群正常对照组FGFR2基因第2内含子SNP位点rs2981582的C/C、C/T和T/T基因型频率分别为31.82%、54.54%和13.64%,而乳腺癌组分别为34.02%、53.61%和12.37%,其基因型和等位基因频率两组相比差异均无统计学意义,P值均>0.05;另一位点rs10510097正常对照组的C/C、C/T和T/T基因型频率分别为60.00%、33.33%和6.67%,乳腺癌组分别为55.31%、36.87%和7.82%,其基因型和等位基因频率两组相比差异均无统计学意义,P值均>0.05。结论:湖北地区人群FGFR2第2内含子2个多态性位点和乳腺癌并无明显相关性。
OBJECTIVE:To explore the relationship between single nucleotide polymorphisms in intron 2 of FGFR2(fibroblast growth factor recepter 2 gene) in Hubei province and breast cancer risk.METHOD:The PCR and DNA sequencing methods were used to analyze the two SNP sites polymorphism(rs2981582 and rs10510097) of the intron 2 of FGFR2 gene in the Han nationality,including 204 breast cancer cases and 192 normal controls.Then calculate the gene and genotype frequencies.RESULTS:The genotype frequencies of C/C,C/T and T/T of the SNP site rs2981582 were 31.82%,54.54% and 13.64% in the controls,and 34.02%,53.61% and 12.37% in breast cancer cases respectively.Compared to the controls,no significant difference was found in the genotype frequencies and allele frequencies(P>0.05).The genotype frequencies of C/C,C/T and T/T of the other site rs10510097 were 60.00%,33.33% and 6.67% in the controls,and 55.31%,36.87% and 7.82% in breast cancer cases respectively.There was no significant difference of the genotype frequencies and allele frequencies between the two groups(P>0.05).CONCLUSION:It indicates these sites have no association with breast cancer.
OBJECTIVE:To explore the relationship between single nucleotide polymorphisms in intron 2 of FGFR2(fibroblast growth factor recepter 2 gene) in Hubei province and breast cancer risk.METHOD:The PCR and DNA sequencing methods were used to analyze the two SNP sites polymorphism(rs2981582 and rs10510097) of the intron 2 of FGFR2 gene in the Han nationality,including 204 breast cancer cases and 192 normal controls.Then calculate the gene and genotype frequencies.RESULTS:The genotype frequencies of C/C,C/T and T/T of the SNP site rs2981582 were 31.82%,54.54% and 13.64% in the controls,and 34.02%,53.61% and 12.37% in breast cancer cases respectively.Compared to the controls,no significant difference was found in the genotype frequencies and allele frequencies(P>0.05).The genotype frequencies of C/C,C/T and T/T of the other site rs10510097 were 60.00%,33.33% and 6.67% in the controls,and 55.31%,36.87% and 7.82% in breast cancer cases respectively.There was no significant difference of the genotype frequencies and allele frequencies between the two groups(P>0.05).CONCLUSION:It indicates these sites have no association with breast cancer.
引文
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[15]Rebbeck T R,Michele A D,Tran T V,et al.Hormone-depend-ent effects of FGFR2 and MAP3K1 in breast cancer susceptibili-ty in a population-based sample of post-menopausal African-A-merican and European-American women[J].Carcinogenesis,2009,30(7):269-274.
[2]周颉,王恩礼.BRCA1的DNA损伤修复与启动子甲基化的研究进展[J].中华肿瘤防治杂志,2008,15(11):866-869.
[3]Miki Y,Swensen J,Shattuck-Eidens D,et al.A strong candi-date for the breast and ovarian-cancer susceptibility gene BRCA1[J].Science,1994,266(5182):66-71.
[4]Wooster R,Bignell G,Lancaster J,et al.Identification of thebreast cancer susceptibility gene BRCA2[J].Nature,1995,378(6559):789-792.
[5]Antoniou A,Pharoah P D P,Narod S,et al.Average risks ofbreast and ovarian cancer associated with mutations in BRCA1 orBRCA2 detected in case series unselected for family history:Acombined analysis of 22 studies[J].Am J Hum Genet,2003,72(5):1117-1130.
[6]Pharoah P D P,Dunning A M,Ponder B A J,et al.Associationstudies for finding cancer-susceptibility genetic variants[J].NatRev Cancer,2004,4(11):850-860.
[7]Shaag A,Walsh T,Renbaum P,et al.Functional and genomicapproaches reveal an ancient CHEK2 allele associated withbreast cancer in the Ashkenazi Jewish population[J].Hum MolGenet,2005,14(4):555-563.
[8]Peto J,Mack T M.High constant incidence in twins and other rela-tives of women with breast cancer[J].Nat Genet,2000,26(4):411-414.
[9]Liu J F,Crepin M,Liu J M,et al.FGF-2 and TPA induce ma-trix metalloproteinase-9 secretion in MCF-7 cells through PKCactivation of the Ras/ERK pathway[J].Biochem Biophys ResCommun,2002,293(4):1174-1182.
[10]Hunter D J,Kraft P,Jacobs K B,et al.A genome-wide associa-tion study identifies alleles in FGFR2 associated with risk of spo-radic postmenopausal breast cancer[J].Nat Genet,2007,39(7):870-874.
[11]Gate M A,Tworoger S S,Terry K L,et al.Breast cancer sus-ceptibility alleles and ovarian cancer risk in 2 study populations[J].Int J Cancer,2009,124(3):729-733.
[12]Easton D F,Pooley K A,Dunning A M,et.al.Genome-wideassociation study identifies novel breast cancer susceptibility loci[J].Nature,2007,447(7148):1087-1095.
[13]Udler M S,Meyer K B,Pooley K A,et al.FGFR2 variants andbreast cancer risk:fine-scale mapping using African Americanstudies and analysis of chromatin conformation[J].Human Mo-lecular Genetics,2009,18(9):1692-1703.
[14]Garcia C M,Hall P,Nevanlinna H,et al.Heterogeneity ofBreast Cancer associations with five susceptibility loci by clinicaland pathological characteristics[J].Plos Genet,2008,4(4):e1000054.
[15]Rebbeck T R,Michele A D,Tran T V,et al.Hormone-depend-ent effects of FGFR2 and MAP3K1 in breast cancer susceptibili-ty in a population-based sample of post-menopausal African-A-merican and European-American women[J].Carcinogenesis,2009,30(7):269-274.
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