云南汉族人群KRAS基因多态性与宫颈癌发生风险的相关性Correlation between KRAS gene polymorphism and occurrence of cervical cancer in Yunnan Han population
梁燕,王磊,雷鸣,顾佳,郑明,张芍,李素艳,陈让,肖云,严志凌
LIANG Yan,WANG Lei,LEI Ming,GU Jia,ZHENG Ming,ZHANG Shao,LI Suyan,CHEN Rang,XIAO Yun,YAN Zhiling
摘要(Abstract):
目的 探讨Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)基因中的单核苷酸多态性位点(SNPs)与云南汉族人群宫颈癌发生风险的相关性。方法 选取云南地区汉族人群宫颈癌患者496例作为病例组、健康个体499例作为对照组,采用TaqMan探针基因分型法对KRAS基因3′-UTR区域3个SNPs位点rs12587(G>T)、rs12245(A>C)、rs1137282(A>G)进行基因分型,并分析其与云南汉族地区人群宫颈癌易感性的相关性。结果 KRAS基因3′-UTR区域3个SNPs位点的等位基因和基因型在病例组和对照组中分布频率比较,差异无统计学意义(P>0.05);单倍型分析结果显示,单倍型rs12587T-rs12245A-rs1137282A在病例组中的分布频率显著低于对照组(P<0.001),该单倍型可能是宫颈癌发生的保护性因素(OR=0.517, 95%CI:0.384~0.697)。结论 KRAS基因3′-UTR区域SNP位点rs12587(G>T)、rs12245(A>C)及rs1137282(A>G)组成的单倍型可能与云南汉族人群宫颈癌发生的风险相关。
Objective To investigate the correlation between single nucleotide polymorphisms(SNPs) in Kirsten rat sarcoma viral oncogene homolog(KRAS) gene and the risk of cervical cancer in Yunnan Han population. Methods A total of 496 cervical cancer patients as case group and 499 healthy controls of Han ethnic group in Yunnan were enrolled in this study. TaqMan probe genotyping method was used to detect three single nucleotide polymorphism(SNP) in KRAS gene rs12587(G>T), rs12245(A>C), rs1137282(A>G), and the correlation between genotype and its susceptibility of cervical cancer in Yunnan Han population was analyzed. Results There was no significant difference in the distribution frequencies of alleles and genotypes of the three SNP loci in the 3'-UTR region of the KRAS gene between case group and control group(P>0.05). Halotype analysis indicated that the halotype frequency of rs12587T-rs12245A-rs1137282A in case group was significantly lower than that of control group(P<0.001). Such halotype could be the protective factor of occurrence of cervical cancer(OR=0.517, 95%CI was 0.384-0.697). Conclusion The SNP loci rs12587(G>T), rs12245(A>C), and rs1137282(A>G) in the 3'-UTR region of KRAS gene might be associated with the risk of cervical cancer in Yunnan Han population.
关键词(KeyWords):
宫颈癌;KRAS基因;SNPs;相关性;云南;汉族
cervical cancer;KRAS gene;single nucleotide polymorphisms(SNPs);correlation;Yunnan;han population
基金项目(Foundation): 云南省教育厅科学研究基金项目(2022J0602);; 云南省科技厅-昆明医科大学应用基础研究联合专项基础研究计划项目(202201AY070001-139)
作者(Author):
梁燕,王磊,雷鸣,顾佳,郑明,张芍,李素艳,陈让,肖云,严志凌
LIANG Yan,WANG Lei,LEI Ming,GU Jia,ZHENG Ming,ZHANG Shao,LI Suyan,CHEN Rang,XIAO Yun,YAN Zhiling
参考文献(References):
- [1] SUNG H,FERLAY J,SIEGEL R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA:a Cancer Journal for Clinicians,2021,71(3):209-249.
- [2] BRIANTI P,FLAMMINEIS E D,MERCURI S R.Review of HPV-related diseases and cancers[J].The New Microbiologica,2017,40(2):80-85.
- [3] NAM A S,CHALIGNE R,LANDAU D A.Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics[J].Nature Reviews Genetics,2021,22(1):3-18.
- [4] TSUCHIDA N,RYDER T,OHTSUBO E.Nucleotide sequence of the oncogene encoding the p21 transforming protein of Kirsten murine sarcoma virus[J].Science,1982,217(4563):937-939.
- [5] MERZ V,GAULE M,ZECCHETTO C,et al.Targeting KRAS:the elephant in the room of epithelial cancers[J].Frontiers in Oncology,2021,11:638360.
- [6] TOMASINI P,WALIA P,LABBE C,et al.Targeting the KRAS pathway in non-small cell lung cancer[J].The Oncologist,2016,21(12):1450-1460.
- [7] TIMAR J,KASHOFER K.Molecular epidemiology and diagnostics of KRAS mutations in human cancer[J].Cancer and Metastasis Reviews,2020,39(4):1029-1038.
- [8] NING L F,RAO W W,YU Y Q,et al.Association between the KRAS gene polymorphisms and papillary thyroid carcinoma in a Chinese Han population[J].Journal of Cancer,2016,7(15):2420-2426.
- [9] 杨晓蕾,周紫云,王小娜,等.LMP7、TAP2基因多态性与云南汉族非小细胞肺癌的相关性[J].贵州医科大学学报,2018,43(3):249-253,304.
- [10]SOLé X,GUINó E,VALLS J,et al.SNPStats:a web tool for the analysis of association studies[J].Bioinformatics,2006,22(15):1928-1929.
- [11]杨佳,刘舒媛,王莹莹,等.云南省汉族人群TNF-α基因多态性与非小细胞肺癌发生、发展的相关性[J].中国癌症杂志,2021,31(7):616-628.
- [12]SHI Y Y,HE L.SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J].Cell Research,2005,15(2):97-98.
- [13]TAYA Y,HOSOGAI K,HIROHASHI S,et al.A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer[J].The EMBO Journal,1984,3(12):2943-2946.
- [14]MURUGAN A K,GRIECO M,TSUCHIDA N.RAS mutations in human cancers:roles in precision medicine[J].Seminars in Cancer Biology,2019,59:23-35.
- [15]ESER S,SCHNIEKE A,SCHNEIDER G,et al.Oncogenic KRAS signalling in pancreatic cancer[J].British Journal of Cancer,2014,111(5):817-822.
- [16]KHAN A Q,KUTTIKRISHNAN S,SIVEEN K S,et al.RAS-mediated oncogenic signaling pathways in human malignancies[J].Seminars in Cancer Biology,2019,54:1-13.
- [17]ZHANG R X,PAN B P,LI Y,et al.SNP rs4937333 in the miRNA-5003-binding site of the ETS1 3′-UTR decreases ETS1 expression[J].Frontiers in Genetics,2019,10:581.
- [18]YU Z B,LI Z,JOLICOEUR N,et al.Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers[J].Nucleic Acids Research,2007,35(13):4535-4541.
- [19]FU W,ZHUO Z J,HUA R X,et al.Association of KRAS and NRAS gene polymorphisms with Wilms tumor risk:a four-center case-control study[J].Aging,2019,11(5):1551-1563.
- [20]SULLIVAN I,SALAZAR J,ARQUEROS C,et al.KRAS genetic variant as a prognostic factor for recurrence in resectable non-small cell lung cancer[J].Clinical & Translational Oncology:Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico,2017,19(7):884-890.
- [21]LIU Q H,LI X D,SONG M Y,et al.Association between C-myc and K-ras gene polymorphisms and non-Hodgkin lymphoma[J].European Review for Medical and Pharmacological Sciences,2020,24(8):4396-4403.
- [22]LIN A,HUA R X,TANG J,et al.KRAS rs7973450 A>G increases neuroblastoma risk in Chinese children:a four-center case-control study[J].Onco Targets and Therapy,2019,12:7289-7295.
- [23]WANG W Y,CHIEN Y C,WONG Y K,et al.Effects of KRAS mutation and polymorphism on the risk and prognosis of oral squamous cell carcinoma[J].Head & Neck,2012,34(5):663-666.
- [24]GUAN Q,YUAN L,LIN A,et al.KRAS gene polymorphisms are associated with the risk of glioma:a two-center case-control study[J].Translational Pediatrics,2021,10(3):579-586.
- [25]DAI Q,WEI H L,HUANG J,et al.KRAS polymorphisms are associated with survival of CRC in Chinese population[J].Tumor Biology,2016,37(4):4727-4734.
文章评论(Comment):
|
||||||||||||||||||
|
||||||||||||||||||
- 宫颈癌
- KRAS基因
- SNPs
- 相关性
- 云南
- 汉族
cervical cancer - KRAS gene
- single nucleotide polymorphisms(SNPs)
- correlation
- Yunnan
- han population
- 梁燕
- 王磊
- 雷鸣
- 顾佳
- 郑明
- 张芍
- 李素艳
- 陈让
- 肖云
- 严志凌
LIANG Yan - WANG Lei
- LEI Ming
- GU Jia
- ZHENG Ming
- ZHANG Shao
- LI Suyan
- CHEN Rang
- XIAO Yun
- YAN Zhiling
- 梁燕
- 王磊
- 雷鸣
- 顾佳
- 郑明
- 张芍
- 李素艳
- 陈让
- 肖云
- 严志凌
LIANG Yan - WANG Lei
- LEI Ming
- GU Jia
- ZHENG Ming
- ZHANG Shao
- LI Suyan
- CHEN Rang
- XIAO Yun
- YAN Zhiling