您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2014, Vol. 52 ›› Issue (11): 106-112.doi: 10.6040/j.issn.1671-7554.0.2014.449

• 公共卫生与管理学 • 上一篇    

脂联素基因和钙蛋白酶10基因多态性与结直肠癌发生风险的关系

刘文辉1, 李晓玲1, 袁萍1, 栾荣生1, 冯斐1, 胡晓琴1, 燕锦2, 杨艳芳1   

  1. 1. 四川大学华西公共卫生学院流行病与卫生统计学系, 四川 成都 610041;
    2. 四川省肿瘤医院肠道外科, 四川 成都 610041
  • 收稿日期:2014-07-08 发布日期:2014-11-10
  • 通讯作者: 杨艳芳.E-mail:yang2009@scu.edu.cn E-mail:yang2009@scu.edu.cn
  • 基金资助:
    国家自然科学基金(81102196);教育部博士点专项科研基金(20090181120019)

Genetic polymorphisms of ADIPOQ and CAPN-10 and colorectal cancer risk

LIU Wenhui1, LI Xiaoling1, YUAN Ping1, LUAN Rongsheng1, FENG Fei1, HU Xiaoqin1, YAN Jin2, YANG Yanfang1   

  1. 1. Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu 610041, Sichuan, China;
    2. Department of Intestinal Surgery, Sichuan Cancer Hospital, Chengdu 610041, Sichuan, China
  • Received:2014-07-08 Published:2014-11-10

摘要: 目的 探讨脂联素基因(ADIPOQ)rs2241766和rs1501299、钙蛋白酶10基因(CAPN-10)rs3842570和rs3792267多态性以及基因之间的交互作用与结直肠癌发生风险的关系.方法 采用1:1匹配的病例对照研究,对400例经组织病理学确诊的结直肠癌原发、新发病例和400例同期未患结直肠癌的健康体检者进行问卷调查,收集两组研究对象的一般情况、生活方式及饮食习惯等资料.应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法检测研究对象ADIPOQ(rs2241766和rs1501299)和CAPN-10(rs3842570和rs3792267)的基因型.采用条件logistic回归模型分析4个位点的基因多态性与结直肠癌发生风险的关系,并应用GMDR法分析4个位点间的交互作用.结果 ADIPOQ rs2241766 TG+GG基因型携带者结直肠癌发生风险较TT型携带者高(OR=1.354,95%CI:1.004~1.827),rs1501299 GT+TT基因型携带者结直肠癌发生风险较GG型携带者低(OR=0.680,95%CI:0.501~0.923);CAPN-10 rs3792267 GA+AA基因型携带者较GG型携带者结直肠癌发生风险高(OR=1.507,95%CI:1.009~2.250),未见 rs3842570 Del/Ins+Ins/Ins基因型与结直肠癌的发生风险有关(OR=1.345,95%CI:0.849~2.130).GMDR法分析结果显示,4个位点在结直肠癌的发生中可能存在交互作用(P=0.001).趋势χ2分析结果表明,风险基因型携带个数与结直肠癌发生风险之间存在剂量-反应关系(χ2=13.302,P<0.001).结论 ADIPOQ(rs2241766和rs1501299)和CAPN-10 rs3792267 多态性可能与结直肠癌的发生风险有关,4个位点间可能存在交互作用,共同影响结直肠癌的发生.

关键词: 基因多态性, 钙蛋白酶10基因, 交互作用, 结直肠癌, 脂联素基因

Abstract: Objective To explore the associations of ADIPOQ (rs2241766, rs1501299) and CAPN-10 (rs3842570, rs3792267) polymorphisms and gene-gene interaction with the risk of colorectal cancer(CRC). Methods A 1:1 matched case-control study was conducted to collect the demographic features, lifestyle, and dietary habits of 400 patients with newly histopathologically diagnosed CRC and 400 matched health controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes of ADIPOQ (rs2241766, rs1501299) and CAPN-10 (rs3842570, rs3792267). Conditional logistic regression was used to analyze the association of genetic polymorphisms of the 4 SNPs and CRC risk. Generalized multifactor dimensionality reduction (GMDR) was applied to test the gene-gene interaction on CRC risk. Results Compared with the wild genotypes, subjects carryingADIPOQ rs2241766 TG+GG genotype and CAPN-10 rs3792267 GA+AA genotype had the increased CRC risk (rs2241766: OR=1.354, 95%CI: 1.004-1.827; rs3792267: OR=1.507, 95%CI: 1.009-2.250), while those carrying ADIPOQ rs1501299 GT+TT genotype had an decreased CRC risk (OR=0.680, 95%CI:0.501-0.923). The association between CAPN-10 rs3842570 Del/Ins+Ins/Ins genotype and CRC risk was not significant (OR=1.345, 95%CI: 0.849-2.130). The GMDR showed that the gene-gene interaction among the 4 locus on CRC risk was significant (P=0.001). A significant dosage effect with an increasing number of risk genotypes was observed as the risk of CRC increased (χ2=13.302, P<0.001). Conclusion ADIPOQ rs2241766, ADIPOQ rs1501299, and CAPN-10 rs3792267 are associated with the risk of CRC, and the 4 locus might affect the risk of CRC together.

Key words: Genetic polymorphisms, Calpain 10 gene, Interactions, Colorectal cancer, Adiponectin gene

中图分类号: 

  • R735.3
[1] Parkin D M, Bray F, Ferlay J, et al.Global cancer statistics, 2002[J].CA Cancer J Clin, 2005, 55(2):74-108.
[2] 郑荣寿, 张思维, 吴良有, 等.中国肿瘤登记地区2008年恶性肿瘤发病和死亡分析[J].中国肿瘤, 2012, 21(1):1-12. ZHENG Rongshou, ZHANG Siwei, WU Liangyou, et al. Report of incidence and mortality from China cancer registries in 2008[J].China Cancer, 2012, 21(1):1-12.
[3] 骆秀婷, 许岸高.糖尿病与结直肠癌相关性的研究进展[J].医学综述, 2013, 19(9):1638-1640. LUO Xiuting, XU Angao.Research progress of relationship between diabetes and colorectal cancer[J].Medical Recapitulate, 2013, 19(9):1638-1640.
[4] Gulcelik M A, Colakoglu K, Dincer H, et al.Associations between adiponectin and two different cancers:breast and colon[J].Asian Pac J Cancer Prev, 2012, 13(1):395-398.
[5] Wei E K, Giovannucci E, Fuchs C S, et al.Low plasma adiponectin levels and risk of colorectal cancer in men:a prospective study[J].J Nati Cancer Inst, 2005, 97(22):1688-1694.
[6] An W, Bai Y, Deng S X, et al.Adiponectin levels in patients with colorectal cancer and adenoma:a meta-analysis[J].Eur J Cancer Prev, 2012, 21(2):126-133.
[7] 吴文君, 卜瑞芳, 沈泓, 等.2型糖尿病与代谢综合征患者血清脂联素水平及脂联素单核苷酸多态性45基因分析[J].临床荟萃, 2009, 24(12):1048-1051. WU Wenjun, BU Ruifang, SHEN Hong, et al. Serum adiponectin level and adiponectin gene SNP45 in patients with type 2 diabetes mellitus and metabolic syndrome[J].Clinical Focus, 2009, 24(12):1048-1051.
[8] AlSaleh A, O'Dell S D, Frost G S, et al.Single nucleotide polymorphisms at the ADIPOQ gene locus interact with age and dietary intake of fat to determine serum adiponectin in subjects at risk of the metabolic syndrome[J].Am J Clin Nutr, 2011, 94(1):262-269.
[9] 路萍, 邵维斌, 夏春英, 等.CAPN-10基因与腹膜透析患者代谢综合征危险因素的关系[J].中国现代医学杂志, 2012, 22(2):55-64. LU Ping, SHAO Weibin, XIA Chunying, et al. Relationship between indel-19 polymorphisms of CAPN-10 gene and risk factors of MS in peritoneal dialysis patients[J].China Journal of Modern Medicine, 2012, 22(2):55-64.
[10] 邓梅香, 陈军建, 俞力, 等.钙蛋白酶10基因多态性与体重和胰岛素抵抗的相关性[J].现代预防医学, 2008, 35(22):4467-4474. DENG Meixiang, CHEN Junjian, YU Li, et al. Association of the CAPN10 gene with body mass index and insulin resistance[J]. Modern Preventive Medicine, 2008, 35(22):4467-4474.
[11] Shima Y, Nakanishi K, Odawara M, et al.Association of the SNP-19 genotype 22 in the calpain-10 gene with elevated body mass index and hemoglobin A1c levels in Japanese[J].Clin Chim Acta, 2003, 336(1-2):89-96.
[12] Horikawa Y, Oda N, Cox N J, et al.Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus[J].Nat Genet, 2000, 26(2):163-175.
[13] 李金娥,刘德敏,张喆.钙蛋白酶10基因多态性与2型糖尿病胰岛素抵抗的研究[J].天津医药,2008,36(2):96-98. LI Jin'e, LIU Demin, ZHANG Zhe.Study on the relationship between the gene polymorphism of CAPN10 and the resistance of type 2 diabetes mellitus[J].Tianjin Med J, 2008, 36(2):96-98.
[14] Li Y, Li X, Shi L, et al.Association of adiponectin SNP+45 and SNP+ 276 with type 2 diabetes in Han Chinese populations:a meta-analysis of 26 case-control studies[J].PLoS One, 2011, 6(5):e19686.
[15] Chung H K, Chae J S, Hyun Y J, et al.Influence of adiponectin gene polymorphisms on adiponectin level and insulin resistance index in response to dietary intervention in overweight-obese patients with impaired fasting glucose or newly diagnosed type 2 diabetes[J].Diabetes Care, 2009, 32(4):552-558.
[16] Hara K, Boutin P, Mori Y, et al.Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population[J].Diabetes, 2002, 51(2):536-540.
[17] Fong P Y, Fesinmeyer M D, White E, et al.Association of diabetes susceptibility gene calpain-10 with pancreatic cancer among smokers[J].J Gastrointest Cancer, 2010, 41(3):203-208.
[18] Moreno-Luna R, Abrante A, Esteban F, et al.Calpain 10 gene and laryngeal cancer:a survival analysis[J].Head Neck, 2011, 33(1):72-76.
[19] Meyer T E, Boerwinkle E, Morrison A C, et al.Diabetes genes and prostate cancer in the atherosclerosis risk in communities study[J].Cancer Epidemiol Biomarkers Prev, 2010, 19(2):558-565.
[20] Johnson J D, Han Z, Otani K, et al.RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets[J]. J Biol Chem, 2004, 279(23):24794-24802.
[1] 乔颖异,岳芳,石兴龙,徐欣颖,吕婧,程传龙,左慧,许青,李秀君. 气象因素和PM2.5及其交互作用对山东省流行性腮腺炎的影响[J]. 山东大学学报 (医学版), 2026, 64(5): 106-115.
[2] 李梓绮,魏闫若雪,刘晓晗,刘春铖,赵然,刘玉昆. 长链非编码RNA HEATR3反义RNA 1参与结直肠癌发生发展的功能及其临床意义[J]. 山东大学学报 (医学版), 2025, 63(9): 108-115.
[3] 杜雪,李春霞,刘云霞,张涛. 基于MFPC-Cox的结直肠癌患者预后动态预测模型[J]. 山东大学学报 (医学版), 2025, 63(5): 101-110.
[4] 王刚,徐鹏演,赵旭安,王海锋,葛苗苗,潘华峰,江志伟. ω-3多不饱和脂肪酸对腹腔镜结直肠癌术后迷走神经和肠功能恢复的影响[J]. 山东大学学报 (医学版), 2025, 63(2): 36-42.
[5] 崔倩倩,李金鹏,吴豫丹,侯志平,孙玮螺,崔盼盼,何培元. 粪便miRNA对结直肠进展期腺瘤无创筛查的临床价值[J]. 山东大学学报 (医学版), 2025, 63(2): 43-50.
[6] 常宇,胡云峰,王会丰,郭静,张跳,郝雅琴,刘雨. 阑尾切除术与结直肠癌发病风险关联的孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(2): 77-83.
[7] 俞静,王刚,王烨,邵明月,潘华峰,葛苗苗,王海锋,江志伟. 基于I-FEED评分系统观察益气导滞方对结直肠癌术后胃肠功能恢复的影响[J]. 山东大学学报 (医学版), 2025, 63(12): 35-43.
[8] 王潇,孔文茹,崔伟亮,王姝麒. 羊角棉总生物碱增强氟尿嘧啶对结直肠癌化疗敏感性[J]. 山东大学学报 (医学版), 2024, 62(6): 30-37.
[9] 魏闫若雪,李梓绮,刘春铖,刘晓晗,赵然,刘玉昆. 结直肠癌中SP1的瘤内异质性表达及其临床意义[J]. 山东大学学报 (医学版), 2024, 62(5): 89-94.
[10] 刘春铖,刘晓晗,魏闫若雪,李梓绮,刘玉昆,赵然. 结直肠癌中含溴结构域蛋白9的亚细胞定位模式及其临床意义[J]. 山东大学学报 (医学版), 2024, 62(4): 24-30.
[11] 于丽,王弋嘉,杨勇,刘学焕,万雪花,包翠萍,苗蓓亮,李斯琪,李静,刘筠. 基于光学表面波技术探究具核梭杆菌介导的自噬与细胞折射率的关系[J]. 山东大学学报 (医学版), 2024, 62(10): 87-97.
[12] 董雅琪,王新慧,赵颖慧,王传新. 血清外泌体LINC02163作为结直肠癌远处转移标志物的临床价值[J]. 山东大学学报 (医学版), 2023, 61(9): 19-28.
[13] 孙富云,王维鹏,张会会,耿艳,安小霞,李双双,张彬彬. 结直肠癌术后患者人格特质与抑郁、焦虑症状的关联性[J]. 山东大学学报 (医学版), 2021, 59(7): 91-96.
[14] 张琳,王燕,马旭,范雪松,袁慧. 不稳定心绞痛患者亚甲基四氢叶酸还原酶基因多态性与血清同型半胱氨酸的相关性[J]. 山东大学学报 (医学版), 2021, 59(6): 71-75.
[15] 杜甜甜,李娟,赵颖慧,段伟丽,王景,王允山,杜鲁涛,王传新. 长链非编码RNA LINC02474在结直肠癌中的表达特征及对细胞增殖的影响[J]. 山东大学学报 (医学版), 2021, 59(10): 59-69.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!