C7基因调节区遗传变异对结直肠癌易感性的影响研究

崔彤 赵丽娜 王思月 张洪梅 张雪梅

崔彤, 赵丽娜, 王思月, 张洪梅, 张雪梅. C7基因调节区遗传变异对结直肠癌易感性的影响研究[J]. 疾病监测, 2023, 38(4): 436-442. doi: 10.3784/jbjc.202211300523
引用本文: 崔彤, 赵丽娜, 王思月, 张洪梅, 张雪梅. C7基因调节区遗传变异对结直肠癌易感性的影响研究[J]. 疾病监测, 2023, 38(4): 436-442. doi: 10.3784/jbjc.202211300523
Cui Tong, Zhao Lina, Wang Siyue, Zhang Hongmei, Zhang Xuemei. Influence of genetic variation in C7 gene regulatory regions on susceptibility to colorectal cancer[J]. Disease Surveillance, 2023, 38(4): 436-442. doi: 10.3784/jbjc.202211300523
Citation: Cui Tong, Zhao Lina, Wang Siyue, Zhang Hongmei, Zhang Xuemei. Influence of genetic variation in C7 gene regulatory regions on susceptibility to colorectal cancer[J]. Disease Surveillance, 2023, 38(4): 436-442. doi: 10.3784/jbjc.202211300523

C7基因调节区遗传变异对结直肠癌易感性的影响研究

doi: 10.3784/jbjc.202211300523
基金项目: 河北省自然科学基金重点项目(No. H2017209233)
详细信息
    作者简介:

    崔彤,女,河北省廊坊市人,硕士研究生在读,主要从事分子流行病学工作,Email:18031789101@163.com

    通讯作者:

    赵丽娜,Tel:0315−8805590,Email:648142060@qq.com

  • 中图分类号: R211; R735.5

Influence of genetic variation in C7 gene regulatory regions on susceptibility to colorectal cancer

Funds: This study was supported by the fund for Key Program of Natural Science Foundation of Hebei Province (No. H2017209233)
More Information
  • 摘要:   目的   探讨补体7(C7)基因遗传变异与结直肠癌易感性的关系。  方法   利用GEPIA数据库分析基因C7在结直肠癌组织与正常组织中的表达差异;利用TIMER数据库分析C7表达及拷贝数变异与结直肠癌免疫细胞浸润的相关关系。 采用病例对照研究分析C7遗传变异对结直肠癌发病风险的影响。 使用PCR-限制性片段长度多态性分析对C7 rs1061429和rs1376178单核苷酸多态性(SNP)进行基因分型。 使用非条件logistic回归计算比值比(OR)和95%置信区间(CI),分析C7 rs1061429和rs1376178遗传变异与结直肠癌易感性的关系。  结果   与结直肠正常组织相比,C7在结直肠癌组织中的表达显著降低(P<0.05)。 C7表达及拷贝数变异可影响结直肠癌免疫细胞浸润。 与C7 rs1061429 CC基因型携带者相比,CA基因型携带者可显著增加直肠癌发病风险(OR=1.42,95%CI:1.08~1.86)。 与C7 rs1376178 CC基因型携带者相比,CA基因型携带者的结肠癌发病风险增加(OR=1.50,95%CI:1.06~2.10),CA或AA基因型携带者有较高的直肠癌发病风险,OR(95%CI)分别为1.46(1.06~2.03)和1.57(1.09~2.28)。 结肠癌易感性的分层分析显示,与C7 rs1376178 CC基因型携带者相比,C7 rs1376178 CA基因型携带者中女性(OR=2.01,95%CI:1.18~3.43)、非吸烟者(OR=1.70,95%CI:1.14~2.54)和非饮酒者(OR=1.57,95%CI:1.06~2.33)的结肠癌发病风险增加。 直肠癌易感性的分层分析表明,与CC 基因型携带者相比,C7 rs1061429 CA基因型携带者中男性(OR=1.64,95%CI:1.17~2.31)、相对低年龄组(OR=1.58,95%CI:1.07~2.33)的直肠癌发病风险增加;与CC基因型携带者相比,C7 rs1376178 AA基因型携带者中女性的直肠癌发病风险增加(OR=1.93,95%CI:1.05~3.54),C7 rs1376178 CA或AA基因型携带者中相对低年龄组(OR=1.86或2.23)、非吸烟者(OR=1.55或1.80)、非饮酒者(OR=1.51或1.62)的直肠癌发病风险增加(P<0.05)。  结论  C7在结直肠癌发生过程中发挥着重要作用,C7 rs1061429和rs1376178多态性可与环境因素交互作用影响结直肠癌易感性。
  • 图  1  基因C7在结直肠癌组织和正常组织中的表达

    注:a. P<0.05

    Figure  1.  Expression of gene C7 in colorectal cancer tissues and normal tissues

    图  2  基因C7表达(A)及拷贝数变异(B)与结直肠癌免疫浸润相关性分析

    注:A. C7表达与免疫浸润的相关性(曲线代表回归线,表示两个变量之间存在非线性相关关系);B. 体细胞C7拷贝数变异与免疫浸润的相关性(不同颜色代表体细胞拷贝数变异类型)

    Figure  2.  Correlation of C7 expression (A) and copy number variation (B) with immune invasion in colorectal cancer

    表  1  研究对象基本特征

    Table  1.   Basic characteristics of the research subjects

     变量结肠癌直肠癌
    病例组对照组Pa病例组对照组Pa
    性别0.9430.838
     男性221 (55.39)222 (55.64)287 (62.39)290 (63.04)
     女性178 (44.61)177 (44.36)173 (37.61)170 (36.96)
    年龄组 (岁)0.3220.843
     ≤60190 (47.62)204 (51.13)232 (50.43)235 (51.09)
     >60209 (52.38)195 (48.87)228 (49.57)225 (48.91)
    吸烟0.7400.553
     是93 (23.31)97 (24.31)121 (26.30)129 (28.04)
     否306 (76.69)302 (75.69)339 (73.70)331 (71.96)
    饮酒0.8650.478
     是90 (22.56)88 (22.06)150 (32.61)140 (30.43)
     否309 (77.44)311 (77.94)310 (67.39)320 (69.57)
    注:a. 双向χ2检验;括号外数据为病例组和对照组例数,括号内数据为各变量例数分别占病例组和对照组例数的百分比(%)
    下载: 导出CSV

    表  2  基因C7 rs1061429和rs1376178遗传变异与结肠癌易感性关系

    Table  2.   Relationship between genetic variation of C7 rs1061429 and rs1376178 and susceptibility to colon cancer

    SNP位点基因型病例组a对照组aOR 值(95%CI bP
    rs1061429CC201(50.38)202(50.63)1.00(参照)
    CA171(42.86)170(42.61)1.01(0.76~1.35)0.941
    AA27(6.76)27(6.876)1.01(0.57~1.77)0.986
    rs1376178CC88(22.06)113(28.32)1.00(参照)
    CA220(55.14)189(47.37)1.50(1.06~2.10)0.020
    AA91(22.80)97(24.31)1.21(0.81~1.80)0.361
    注:SNP. 单核苷酸多态性;a. 括号外数据为各基因型的例数,括号内数据为各基因型的例数分别占病例组和对照组例数的百分比(%);b. 非条件logistic回归分析,并根据性别、年龄、饮酒和吸烟状况进行校正
    下载: 导出CSV

    表  3  基因C7 rs1061429和rs1376178遗传变异与直肠癌易感性关系

    Table  3.   Relationship between genetic variation of C7 rs1061429 and rs1376178 and susceptibility to rectal cancer

    SNP位点基因型病例组a对照组aOR 值(95%CIbP
    rs1061429CC203(44.13)240(52.17)1.00(参照)
    CA220(47.83)183(39.78)1.42(1.08~1.86)0.011
    AA37(8.04)37(8.05)1.18(0.72~1.94)0.505
    rs1376178CC90(19.57)123(26.74)1.00(参照)
    CA240(52.17)224(48.70)1.46(1.06~2.03)0.022
    AA130(28.26)113(24.56)1.57(1.09~2.28)0.017
    注:SNP. 单核苷酸多态;a. 括号外数据为各基因型的例数,括号内数据为各基因型的例数分别占病例组和对照组例数的百分比(%);b. 非条件logistic回归分析,并根据性别、年龄、饮酒和吸烟状况进行校正
    下载: 导出CSV

    表  4  基因C7 rs1376178遗传变异与结肠癌发病风险关系分层分析

    Table  4.   Stratified analysis on relationship between genetic variation of C7 rs1376178 and risk of colon cancer

     变量不同基因型病例组/对照组例数CA/CCOR值(95 %CIaPAA/CCOR值(95 %CIaP
    CCCAAA
    性别
     男性57/61122/10742/541.21 (0.77~1.89)0.4070.83 (0.48~1.43)0.498
     女性31/5298/8249/432.01 (1.18~3.43)0.0101.90 (1.03~3.48)0.040
    年龄组(岁)
     ≤6042/5897/9751/491.37 (0.84~2.23)0.2081.40 (0.80~2.45)0.245
     >6046/55123/9240/481.58 (0.98~2.55)0.0630.98 (0.55~1.76)0.955
    吸烟
     是27/2851/5215/170.94 (0.48~1.83)0.8480.91 (0.38~2.21)0.836
     否61/85169/13776/801.70 (1.14~2.54)0.0091.31 (0.83~2.08)0.241
    饮酒
     是23/2651/4816/141.06 (0.52~2.14)0.8721.26 (0.50~3.16)0.625
     否65/87169/14175/831.57 (1.06~2.33)0.0241.18 (0.75~1.85)0.484
    注:a. 非条件logistic回归,并根据性别、年龄、饮酒和吸烟状况进行校正
    下载: 导出CSV

    表  5  基因C7 rs1061429遗传变异与直肠癌发病风险关系分层分析

    Table  5.   Stratified analysis on relationship between genetic variation of C7 rs1061429 and risk of rectal cancer

     变量不同基因型病例组/对照组例数CA/CCOR值(95 %CIaPAA/CCOR值(95 %CIaP
    CCCAAA
    性别
     男性123/160143/11221/181.64 (1.17~2.31)0.0051.43 (0.72~2.82)0.303
     女性80/8077/7116/191.00 (0.63~1.58)0.9860.87 (0.41~1.83)0.705
    年龄组(岁)
     ≤60104/129110/8918/171.58 (1.07~2.33)0.0211.22 (0.59~2.51)0.590
     >6099/111110/9419/201.28 (0.86~1.89)0.2211.20 (0.60~2.41)0.601
    吸烟
     是53/6865/523/91.62 (0.96~2.76)0.0730.35 (0.08~1.42)0.141
     否150/172155/13134/281.35 (0.98~1.87)0.0651.48 (0.85~2.56)0.164
    饮酒
     是66/7481/593/71.37 (0.84~2.25)0.2120.40 (0.09~1.74)0.221
     否137/166139/12434/301.36 (0.98~1.90)0.0691.41 (0.82~2.42)0.219
    注:a. 非条件logistic回归,并根据性别、年龄、饮酒和吸烟状况进行校正
    下载: 导出CSV

    表  6  基因C7 rs1376178遗传变异与直肠癌发病风险关系分层分析

    Table  6.   Stratified analysis on relationship between genetic variation of C7 rs1376178 and risk of rectal cancer

     变量不同基因型病例组/对照组例数CA/CCOR值(95 %CIaPAA/CCOR值(95 %CIaP
    CCCAAA
    性别
     男性57/74155/14875/681.39 (0.92~2.10)0.1231.44 (0.89~2.32)0.140
     女性33/4985/7655/451.66 (0.95~2.89)0.0751.93 (1.05~3.54)0.035
    年龄组(岁)
     ≤6039/66122/11671/531.86 (1.15~3.01)0.0112.23 (1.30~3.83)0.004
     >6051/57118/10859/601.18 (0.74~1.88)0.4831.14 (0.67~1.93)0.630
    吸烟
     是25/3272/7024/271.32 (0.70~2.49)0.3931.14 (0.52~2.49)0.736
     否65/91168/154106/861.55 (1.05~2.28)0.0291.80 (1.17~2.76)0.008
    饮酒
     是33/3982/7435/271.27 (0.70~2.29)0.4291.58 (0.77~3.24)0.217
     否57/84158/15095/861.51 (1.00~2.26)0.0481.62 (1.04~2.53)0.035
    注:a. 非条件logistic回归,并根据性别、年龄、饮酒和吸烟状况进行校正
    下载: 导出CSV
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  • 收稿日期:  2022-11-30
  • 网络出版日期:  2023-03-13
  • 刊出日期:  2023-04-30

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