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EGFR基因多态性与云南汉族人群非小细胞肺癌的关联性

李盈甫 郭妮 罗正光 邢安灏 李太福 马千里

李盈甫, 郭妮, 罗正光, 邢安灏, 李太福, 马千里. EGFR基因多态性与云南汉族人群非小细胞肺癌的关联性[J]. 昆明医科大学学报, 2025, 46(4): 99-108. doi: 10.12259/j.issn.2095-610X.S20250413
引用本文: 李盈甫, 郭妮, 罗正光, 邢安灏, 李太福, 马千里. EGFR基因多态性与云南汉族人群非小细胞肺癌的关联性[J]. 昆明医科大学学报, 2025, 46(4): 99-108. doi: 10.12259/j.issn.2095-610X.S20250413
Yingfu LI, Ni GUO, Zhengguang LUO, Anhao XING, Taifu LI, Qianli MA. Correlation of EGFR Gene Polymorphisms with Non-small Cell Lung Cancer in Yunnan Han Population[J]. Journal of Kunming Medical University, 2025, 46(4): 99-108. doi: 10.12259/j.issn.2095-610X.S20250413
Citation: Yingfu LI, Ni GUO, Zhengguang LUO, Anhao XING, Taifu LI, Qianli MA. Correlation of EGFR Gene Polymorphisms with Non-small Cell Lung Cancer in Yunnan Han Population[J]. Journal of Kunming Medical University, 2025, 46(4): 99-108. doi: 10.12259/j.issn.2095-610X.S20250413

EGFR基因多态性与云南汉族人群非小细胞肺癌的关联性

doi: 10.12259/j.issn.2095-610X.S20250413
基金项目: 云南省科技厅-昆明医科大学应用基础研究联合专项基金(202201AY070001-141); 保山市科技计划项目-医学研究联合专项基金(2023bskjylms016)
详细信息
    作者简介:

    李盈甫(1978 ~ ),男,云南昆明人,医学硕士,副主任医师,主要从事肺癌发生机制研究工作。郭妮与李盈甫对本文有同等贡献

    通讯作者:

    李太福,E-mail:185237636@qq.com

    马千里,E-mail:maqianli78@126.com

  • 中图分类号: R734.2

Correlation of EGFR Gene Polymorphisms with Non-small Cell Lung Cancer in Yunnan Han Population

  • 摘要:   目的  评估云南汉族人群中表皮生长因子受体(epidermal growth factor receptor,EGFR)基因多态性与非小细胞肺癌(non-small cell lung cancer,NSCLC)的相关性。  方法  本研究共纳入407例NSCLC患者及526例健康对照者。采用TaqMan探针法对EGFR上的5个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点(rs1050171、rs2072454、rs2227983、rs1140475和rs2293347)进行基因分型检测,并分析5个SNPs位点与NSCLC以及病理类型的相关性。  结果  在显性模式下,rs2072454位点的C/T-T/T相对于C/C可能是NSCLC发生的风险因素(P = 0.004;OR = 1.50,95%CI 1.14~1.96)。在鳞状细胞癌(squamous cell carcinoma,SCC)组与对照组间基因型频率差异有统计学意义(P = 0.007),但等位基因频率经过Bonferroni校正后无差异(P > 0.01);在显性模式下,该位点的C/T-T/T相对于C/C来说是NSCLC中腺癌(adenocarcinoma,AC)发生的风险因素(P = 0.002;OR = 1.86,95%CI 1.24~2.80)。在隐性模式下,rs1050171位点携带A/A基因型的个体患鳞癌的风险显著升高(P = 0.006,OR = 2.66,95%CI 1.33~5.33)。显性模式下,rs2227983位点的A/G-G/G相对于A/A来说是NSCLC中SCC发生的风险因素(P = 0.007;OR = 1.83,95%CI 1.15~2.89)。  结论  EGFR基因SNP位点rs2072454、rs1050171、rs2227983可能与云南汉族人群NSCLC发生风险相关,且与病理类型相关。
  • 图  1  EGFR基因的5个SNP位点测序图

    A:rs1050171测序峰图;B:rs2072454测序峰图;C:rs2227983测序峰图;D:rs1140475测序峰图;E:rs2293347测序峰图。

    Figure  1.  Sequencing of 5 SNPs in EGFR gene

    表  1  EGFR基因5个SNP位点在NSCLC组和对照组间基因型频率分布 [n(%)]

    Table  1.   Genotype frequency distribution of 5 SNPs in EGFR gene between the NSCLC group and the control group [n(%)]

    SNPs 基因型 对照组 NSCLC组 χ2 P P(HWE)
    rs1050171 AA 15 (2.9) 24 (5.9) 5.575 0.062 0.985
      AG 148 (28.1) 117 (28.7)
      GG 363 (69.0) 266 (65.4)
    rs2072454 CC 214 (40.7) 128 (31.4) 9.118 0.010 0.999
      CT 243 (46.2) 225 (55.3)
      TT 69 (13.1) 54 (13.3)
    rs2227983 AA 155 (29.5) 98 (24.1) 3.628 0.163 0.919
      AG 260 (49.4) 222 (54.5)
      GG 111 (21.1) 87 (21.4)
    rs1140475 CC 471 (89.5) 368 (90.4) 1.185 0.553 0.053
      CT 51 (9.7) 38 (9.3)
      TT 4 (0.8) 1 (0.2)
    rs2293347 CC 266 (50.6) 230 (56.5) 4.490 0.106 0.125
      CT 226 (43.0) 147 (36.1)
      TT 34 (6.5) 30 (7.4)
      Bonferroni校正,n = 5。
    下载: 导出CSV

    表  2  EGFR基因5个SNP位点在NSCLC组和对照组间等位基因频率分布 [n(%)]

    Table  2.   Allele frequency distribution of 5 SNPs in EGFR gene between the NSCLC group and the control group [n(%)]

    SNPs 等位基因 对照组 NSCLC组 OR (95%CI χ2 P
    rs1050171 A 178 (16.9) 165 (20.3) 1.25 (0.99~1.58) 3.433 0.064
      G 874 (83.1) 649 (79.7)
    rs2072454 C 671 (63.8) 481 (59.1) 0.82 (0.68~0.99) 4.277 0.039
      T 381 (36.2) 333 (40.9)
    rs2227983 A 570 (54.2) 418 (51.4) 0.89 (0.74~1.07) 1.476 0.224
      G 482 (45.8) 396 (48.6)  
    rs1140475 C 993 (94.4) 774 (95.1) 1.15 (0.76~1.74) 0.440 0.507
      T 59 (5.6) 40 (4.9)  
    rs2293347 C 758 (72.1) 607 (74.6) 1.14 (0.92~1.40) 1.480 0.224
      T 294 (27.9) 207 (25.4)  
      Bonferroni校正,n = 5。
    下载: 导出CSV

    表  3  EGFR基因5个SNP位点在NSCLC组和对照组相关性的遗传模型分析 [n(%)]

    Table  3.   The inheritance analysis of five SNPs between NSCLC and control group [n(%)]

    SNPs 遗传模型 基因型 对照组 NSCLC组 OR (95% CI) P AIC BIC
    rs1050171 共显性 G/G 363 (69.0) 266 (65.4) 1 0.060 1278.7 1293.2
        A/G 148 (28.1) 117 (28.7) 1.08 (0.81~1.44)
        A/A 15 (2.9) 24 (5.9) 2.18 (1.12~4.24)
      显性 G/G 363 (69.0) 266 (65.4) 1 0.240 1280.8 1290.5
        A/G-A/A 163 (31.0) 141 (34.6) 1.18 (0.90~1.55)
      隐性 G/G-A/G 511 (97.2) 383 (94.1) 1 0.020 1276.9 1286.6
        A/A 15 (2.8) 24 (5.9) 2.13 (1.10~4.12)
      超显性 G/G-A/A 378 (71.9) 290 (71.2) 1 0.840 1282.2 1291.8
        A/G 148 (28.1) 117 (28.8) 1.03 (0.77~1.37)
      逻辑累加 --- --- --- 1.23 (0.98~1.55) 0.070 1278.9 1288.6
    rs2072454 共显性 C/C 214 (40.7) 128 (31.4) 1 0.010 1275 1289.5
        C/T 243 (46.2) 225 (55.3) 1.55 (1.16~2.06)
        T/T 69 (13.1) 54 (13.3) 1.31 (0.86~1.99)
      显性 C/C 214 (40.7) 128 (31.4) 1 0.004* 1273.7 1283.4
        C/T-T/T 312 (59.3) 279 (68.6) 1.50 (1.14~1.96)
      隐性 C/C-C/T 457 (86.9) 353 (86.7) 1 0.950 1282.2 1291.9
        T/T 69 (13.1) 54 (13.3) 1.01 (0.69~1.48)
      超显性 C/C-T/T 283 (53.8) 182 (44.7) 1 0.006* 1274.6 1284.3
        C/T 243 (46.2) 225 (55.3) 1.44 (1.11~1.87)
      逻辑累加 --- --- --- 1.24 (1.02~1.50) 0.030 1277.6 1287.3
    rs2227983 共显性 A/A 155 (29.5) 98 (24.1) 1 0.160 1280.5 1295.1
        A/G 260 (49.4) 222 (54.5) 1.35 (0.99~1.84)
        G/G 111 (21.1) 87 (21.4) 1.24 (0.85~1.81)
      显性 A/A 155 (29.5) 98 (24.1) 1 0.070 1278.8 1288.5
        A/G-G/G 371 (70.5) 309 (75.9) 1.32 (0.98~1.77)
      隐性 A/A-A/G 415 (78.9) 320 (78.6) 1 0.920 1282.2 1291.9
        G/G 111 (21.1) 87 (21.4) 1.02 (0.74~1.39)
      超显性 A/A-G/G 266 (50.6) 185 (45.5) 1 0.120 1279.8 1289.5
        A/G 260 (49.4) 222 (54.5) 1.23 (0.95~1.59)
      逻辑累加 --- --- --- 1.13 (0.93~1.36) 0.220 1280.7 1290.3
    rs1140475 共显性 C/C 471 (89.5) 368 (90.4) 1 0.520 1282.9 1297.4
        C/T 51 (9.7) 38 (9.4) 0.95 (0.61~1.48)
        T/T 4 (0.8) 1 (0.2) 0.32 (0.04~2.87)
      显性 C/C 471 (89.5) 368 (90.4) 1 0.660 1282 1291.7
        C/T-T/T 55 (10.5) 39 (9.6) 0.91 (0.59~1.40)
      隐性 C/C-C/T 522 (99.2) 406 (99.8) 1 0.260 1280.9 1290.6
        T/T 4 (0.8) 1 (0.2) 0.32 (0.04~2.88)
      超显性 C/C-T/T 475 (90.3) 369 (90.7) 1 0.850 1282.2 1291.8
        C/T 51 (9.7) 38 (9.3) 0.96 (0.62~1.49)
      逻辑累加 --- --- --- 0.88 (0.59~1.31) 0.520 1281.8 1291.4
    rs2293347 共显性 C/C 266 (50.5) 230 (56.5) 1 0.110 1279.7 1294.2
        C/T 226 (43.0) 147 (36.1) 0.75 (0.57~0.99)
        T/T 34 (6.5) 30 (7.4) 1.02 (0.61~1.72)
      显性 C/C 266 (50.6) 230 (56.5) 1 0.070 1278.9 1288.6
        C/T-T/T 260 (49.4) 177 (43.5) 0.79 (0.61~1.02)
      隐性 C/C-C/T 492 (93.5) 377 (92.6) 1 0.590 1281.9 1291.6
        T/T 34 (6.5) 30 (7.4) 1.15 (0.69~1.92)
      超显性 C/C-T/T 300 (57.0) 260 (63.9) 1 0.030 1277.7 1287.4
        C/T 226 (43.0) 147 (36.1) 0.75 (0.58~0.98)
      逻辑累加 --- --- --- 0.88 (0.71~1.08) 0.220 1280.7 1290.4
      *P < 0.01(Bonferroni校正,n = 5)。
    下载: 导出CSV

    表  4  EGFR基因中5个SNP位点在AC组、SCC组和对照组间基因型频率分布 [n(%)]

    Table  4.   Genotype frequency distribution of 5 SNPs in EGFR gene among AC,SCC and control groups [n(%)]

    SNPs 基因型 对照组 AC组 SCC组 AC组vs对照组 SCC组vs对照组
    χ2 P χ2 P
    rs1050171 AA 15 (2.9) 19 (7.3) 5 (3.4) 8.483 0.014 0.197 0.906
      AG 148 (28.1) 75 (28.6) 42 (29.0)
      GG 363 (69.0) 168 (64.1) 98 (67.6)
    rs2072454 CC 214 (40.7) 89 (34.0) 39 (26.9) 3.749 0.153 9.756 0.008*
      CT 243 (46.2) 139 (53.1) 86 (59.3)
      TT 69 (13.1) 34 (13.0) 20 (13.8)
    rs2227983 AA 155 (29.5) 71 (27.1) 27 (18.6) 0.491 0.782 8.117 0.017
      AG 260 (49.4) 133 (50.8) 89 (61.4)
      GG 111 (21.1) 58 (22.1) 29 (20.0)
    rs1140475 CC 471 (89.5) 238 (90.8) 130 (89.6) 2.077 0.354 0.008 0.996
      CT 51 (9.7) 24 (9.2) 14 (9.7)
      TT 4 (0.8) 0 (0.0) 1 (0.7)
    rs2293347 CC 266 (50.5) 150 (57.3) 80 (55.2) 4.499 0.106 1.187 0.552
      CT 226 (43.0) 92 (35.1) 55 (37.9)
      TT 34 (6.5) 20 (7.6) 10 (6.9)
      *P < 0.01(Bonferroni校正,n = 5)。
    下载: 导出CSV

    表  5  EGFR基因5个SNP位点在在AC组、SCC组和对照组间等位基因频率分布 [n(%)]

    Table  5.   Allele frequency distribution of 5 SNPs in EGFR gene among the AC group,SCC group,and control group [n(%)]

    SNPs 等位基因 对照组 AC组 SCC组 AC组vs对照组 SCC组vs对照组
    χ2 P OR (95%CI χ2 P OR (95%CI
    rs1050171 A 178 (16.9) 113 (21.6) 52 (17.9) 0.025 1.35 (1.04~1.76) 0.164 0.686 1.07 (0.76~1.51)
      G 874 (83.1) 411 (78.4) 238 (82.1)
    rs2072454 C 671 (63.8) 317 (60.5) 164 (56.6) 0.204 0.87 (0.70~1.08) 5.057 0.025 0.74 (0.57~0.96)
      T 381 (36.2) 207 (39.5) 126 (43.4)
    rs2227983 A 570 (54.2) 275 (52.5) 143 (49.3) 0.523 0.93 (0.76~1.15) 2.167 0.141 0.82 (0.63~1.07)
      G 482 (45.8) 249 (47.5) 147 (50.7)
    rs1140475 C 993 (94.4) 500 (95.4) 274 (94.5) 0.389 1.24 (0.76~2.01) 0.004 0.952 1.02 (0.58~1.80)
      T 59 (5.6) 24 (4.6) 16 (5.5)
    rs2293347 C 758 (72.1) 392 (74.8) 215 (74.1) 0.246 1.15 (0.91~1.46) 0.495 0.481 1.11 (0.83~1.50)
    T 294 (27.9) 132 (25.2) 75 (25.9)
      Bonferroni校正,n = 5。
    下载: 导出CSV

    表  6  EGFR基因5个SNP位点在AC组、SCC组和对照组相关性的遗传模型分析 [n(%)](1)

    Table  6.   The inheritance analysis of five SNPs among AC,SCC and control groups [n(%)](1)

    SNPs遗传模型基因型对照组AC组SCC组AC组vs对照组SCC组vs对照组
    OR (95%CIPAICBICOR (95%CIPAICBIC
    rs1050171共显性G/G363 (69.0)168 (64.1)98 (67.5)10.0201000.31014.310.910706.2719.8
      A/G148 (28.1)75 (28.6)42 (29.0)1.09 (0.79~1.53)1.05 (0.70~1.58)
      A/A15 (2.8)19 (7.3)5 (3.5)2.74 (1.36~5.52)1.23 (0.44~3.48)
     显性G/G363 (69.0)168 (64.1)98 (67.6)10.1701004.31013.710.740704.3713.3
      A/G-A/A163 (31.0)94 (35.9)47 (32.4)1.25 (0.91~1.70)1.07 (0.72~1.58)
     隐性G/G-A/G511 (97.2)243 (92.8)140 (96.5)10.006*998.61007.910.710704.3713.3
      A/A15 (2.8)19 (7.2)5 (3.5)2.66 (1.33~5.33)1.22 (0.43~3.41)
     超显性G/G-A/A378 (71.9)187 (71.4)103 (71.0)10.8901006.21015.510.840704.4713.4
      A/G148 (28.1)75 (28.6)42 (29.0)1.02 (0.74~1.42)1.04 (0.69~1.56)
     逻辑累加------------1.33 (1.03~1.72)0.0301001.61010.91.07 (0.76~1.51)0.690704.3713.3
    rs2072454共显性C/C214 (40.7)89 (34.0)39 (26.9)10.1501004.51018.510.006*696.4709.9
      C/T243 (46.2)139 (53.0)86 (59.3)1.38 (1.00~1.90)1.94 (1.28~2.96)
      T/T69 (13.1)34 (13.0)20 (13.8)1.18 (0.73~1.91)1.59 (0.87~2.91)
     显性C/C214 (40.7)89 (34.0)39 (26.9)10.0701002.91012.210.002*694.9703.9
      C/T-T/T312 (59.3)173 (66.0)106 (73.1)1.33 (0.98~1.82)1.86 (1.24~2.80)
     隐性C/C-C/T457 (86.9)228 (87.0)125 (86.2)10.9601006.21015.610.830704.4713.4
      T/T69 (13.1)34 (13.0)20 (13.8)0.99 (0.64~1.53)1.06 (0.62~1.81)
     超显性C/C-T/T283 (53.8)123 (47.0)59 (40.7)10.0701002.91012.310.005*696.6705.6
      C/T243 (46.2)139 (53.0)86 (59.3)1.32 (0.98~1.77)1.70 (1.17~2.47)
     逻辑累加------------1.16 (0.93~1.44)0.2001004.51013.91.37 (1.05~1.80)0.020699.2708.2
    rs2227983共显性A/A155 (29.5)71 (27.1)27 (18.6)10.7801007.71021.710.020698711.5
      A/G260 (49.4)133 (50.8)89 (61.4)1.12 (0.79~1.58)1.97 (1.22~3.16)
      G/G111 (21.1)58 (22.1)29 (20.0)1.14 (0.75~1.74)1.50 (0.84~2.67)
     显性A/A155 (29.5)71 (27.1)27 (18.6)10.4901005.71015.110.007*697.2706.3
      A/G-G/G371 (70.5)191 (72.9)118 (81.4)1.12 (0.81~1.56)1.83 (1.15~2.89)
     隐性A/A-A/G415 (78.9)204 (77.9)116 (80.0)10.7401006.11015.410.770704.3713.4
      G/G111 (21.1)58 (22.1)29 (20.0)1.06 (0.74~1.52)0.93 (0.59~1.48)
     超显性A/A-G/G266 (50.6)129 (49.2)56 (38.6)10.7201006.11015.410.010697.9706.9
      A/G260 (49.4)133 (50.8)89 (61.4)1.05 (0.78~1.42)1.63 (1.12~2.37)
     逻辑累加------------1.07 (0.87~1.32)0.5201005.81015.21.23 (0.94~1.60)0.130702.2711.2
    下载: 导出CSV

    表  6  EGFR基因5个SNP位点在AC组、SCC组和对照组相关性的遗传模型分析 [n(%)](2)

    Table  6.   The inheritance analysis of five SNPs among AC,SCC and control groups [n(%)](2)

    SNPs遗传模型基因型对照组AC组SCC组AC组vs对照组SCC组vs对照组
    OR (95%CIPAICBICOR (95%CIPAICBIC
    rs1140475共显性C/C471 (89.5)238 (90.8)130 (89.7)10.1901004.91018.911.000706.4719.9
      C/T51 (9.7)24 (9.2)14 (9.7)0.93 (0.56~1.55)0.99 (0.53~1.85)
      T/T4 (0.8)0 (0.0)1 (0.7)0.000.91 (0.10~8.17)
     显性C/C471 (89.5)238 (90.8)130 (89.7)10.5701005.91015.210.970704.4713.4
      C/T-T/T55 (10.5)24 (9.2)15 (10.3)0.86 (0.52~1.43)0.99 (0.54~1.81)
     隐性C/C-C/T522 (99.2)262 (100.0)144 (99.3)10.07010031012.310.930704.4713.4
      T/T4 (0.8)0 (0.0)1 (0.7)0.000.91 (0.10~8.17)
     超显性C/C-T/T475 (90.3)238 (90.8)131 (90.3)10.8101006.21015.510.990704.4713.4
      C/T51 (9.7)24 (9.2)14 (9.7)0.94 (0.56~1.56)1.00 (0.53~1.85)
     逻辑累加------------0.82 (0.51~1.31)0.3901005.51014.80.98 (0.57~1.70)0.950704.4713.4
    rs2293347共显性C/C266 (50.5)150 (57.2)80 (55.2)10.1001003.71017.710.550705.2718.7
      C/T226 (43.0)92 (35.1)55 (37.9)0.72 (0.53~0.99)0.81 (0.55~1.19)
      T/T34 (6.5)20 (7.6)10 (6.9)1.04 (0.58~1.88)0.98 (0.46~2.07)
     显性C/C266 (50.6)150 (57.2)80 (55.2)10.0801003.11012.410.330703.5712.5
      C/T-T/T260 (49.4)112 (42.8)65 (44.8)0.76 (0.57~1.03)0.83 (0.57~1.20)
     隐性C/C-C/T492 (93.5)242 (92.4)135 (93.1)10.5401005.91015.210.850704.4713.4
      T/T34 (6.5)20 (7.6)10 (6.9)1.20 (0.67~2.12)1.07 (0.52~2.23)
     超显性C/C-T/T300 (57.0)170 (64.9)90 (62.1)10.0301001.7101110.270703.2712.2
      C/T226 (43.0)92 (35.1)55 (37.9)0.72 (0.53~0.98)0.81 (0.56~1.18)
     逻辑累加------------0.87 (0.68~1.10)0.2401004.81014.20.89 (0.66~1.21)0.470703.9712.9
      *P < 0.01 (Bonferroni 校正,n = 5)。
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  • 收稿日期:  2024-12-16
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