Correlation between estrogen receptor alpha gene polymorphism and risk of bladder cancer
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摘要:
目的 研究雌激素受体α基因单核苷酸多态性与膀胱癌易感性的关系。 方法 从两医院收集膀胱癌新发病例220例及同期健康体检对照220例，通过问卷收集研究对象一般情况，查阅电子病历收集临床检查资料；用多重高温连接酶检测反应技术（improved multiple ligase detection reaction，iMLDR）检测基因型；采用酶联免疫法检测两组血清中雌激素受体α（estrogen receptor alpha，ESRα）的表达量。 结果 病例组的体重指数、饮食及生活行为习惯和血红蛋白、中性粒细胞百分率等临床检查结果与对照组人群差异均有统计学意义（均有P < 0.05）。rs1801132位点基因及基因型频率与病理分级（χ2=9.607，P=0.022；χ2=24.468，P < 0.001）、远处转移（χ2=2.367，P=0.027；χ2=21.758，P=0.001）有关。膀胱癌患者血清中ESRα受体表达量低于正常人群（t=5.588，P < 0.001）。rs1801132位点多态性在不同基因型人群中膀胱癌发病风险均有统计学差异[GG：OR（95% CI）=0.325（0.141~0.751），P=0.009；GC：OR（95% CI）=0.409（0.198~0.847），P=0.016]。 结论 rs1801132位点多态性与膀胱癌发病相关，GG/GC基因型在膀胱癌中具有保护作用；rs2234693位点多态性与膀胱癌无相关性。 Abstract:Objective To study the relationship between single nucleotide polymorphisms of estrogen receptor alpha gene and susceptibility to bladder cancer. Methods 220 new cases of bladder cancer patients and 220 healthy controls were collected from two hospitals. The general demographic characteristics of the study subjects was collected through questionnaires. Electronic medical records were used to collect clinical examination data. Detection of genotypes was detected by improved multiple ligase detection reaction (iMLDR). Enzyme-linked immunosorbent assay was used to detect the expression of estrogen receptor alpha (ESRα) in the serum of cases and control groups. Results The body mass index, diet and other habits of the case group and clinical examination results such as hemoglobin and neutrophil percentage were significantly different from those of the control group (all P < 0.05). The rs1801132 locus gene and genotype frequency were related to pathological grade (χ2 = 9.607, P = 0.022;χ2 = 24.468, P < 0.001) and distant metastasis (χ2 = 2.367, P = 0.027;χ2 = 21.758, P = 0.001). The expression of ESRα receptor in the serum of bladder cancer patients was significantly lower than that in the normal population (t=5.588, P < 0.001). The polymorphism of rs1801132 locus was statistically different in bladder cancer risk among different genotype populations [GG:OR (95% CI) = 0.325 (0.141-0.751), P = 0.009; GC: OR (95% CI) = 0.409 (0.198-0.847), P = 0.016]. Conclusion The polymorphism of the rs1801132 is associated with bladder cancer, and the GG/GC genotype plays a protective role in bladder cancer. There was no correlation between rs2234693 polymorphism and bladder cancer. -
表 1 两组人群一般资料及临床检查资料比较(x ±s)
Table 1. Comparison of general and clinical data between the two groups(x ±s)
指标 病例(n=220) 对照(n=220) t/χ2值 P值 吸烟史(年) 37.79±12.36 34.29±12.23 2.13 0.034 饮酒史(年) 34.64±10.81 29.30±11.18 2.93 0.004 BMI(kg/m2) 24.38±2.65 23.82±2.71 2.09 0.037 HGB(g/L) 139.87±22.28 144.61±19.28 2.39 0.017 RBC(×1012/L) 5.84±13.57 4.78±0.52 1.16 0.250 WBC(×109/L) 7.32±3.03 10.28±50.02 0.88 0.382 NE% 64.11±12.22 61.36±11.23 2.48 0.013 民族 8.30 0.016 汉 206 191 蒙 11 15 其他 3 14 劳动类型 77.46 < 0.001 脑力 62 63 体力 145 72 无 13 85 农药接触 17.33 < 0.001 是 58 24 否 162 196 食物咸淡 29.99 < 0.001 较咸 83 33 适中 77 114 偏淡 60 73 水果摄入 19.14 < 0.001 经常 109 154 偶尔/不 111 66 煎炸食品 1.09 0.297 经常 15 21 偶尔/不 205 199 日常情绪 13.64 < 0.001 紧张 20 48 轻松 200 172 憋尿 13.40 0.001 经常 23 20 偶尔 93 59 否 104 141 锻炼 7.21 0.007 经常 108 136 偶尔/不 112 84 
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表 2 rs1801132位点等位基因/基因型频率与膀胱癌临床病理特征关系
Table 2. Relationship between allele / genotype frequency of rs1801132 locus and clinicopathological characteristics of bladder cancer
指标 等位基因 χ2值 P值 基因型 χ2值 P值 G C G/G G/C C/C 病理类型 2.342 0.310 4.539 0.338 颗粒型 1 3 0 1 1 上皮型 78 76 24 30 23 其他型 125 157 28 69 44 病理分级 9.607 0.022 24.468 < 0.001 Ⅰ 33 37 9 15 11 Ⅱ 29 61 10 9 26 Ⅲ 14 16 4 6 5 其他 128 122 29 70 26 临床分期 2.984 0.394 5.308 0.505 Ⅰ 55 55 17 21 17 Ⅱ 5 9 1 3 3 Ⅲ 0 2 0 0 1 其他 144 170 34 76 47 远处转移 2.367 0.027 21.758 0.001 MX 2 4 1 0 2 M0 55 77 16 23 27 M1 2 12 1 0 6 其他 145 143 34 77 33
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表 3 rs2234693位点等位基因/基因型频率与膀胱癌临床病理特征关系
Table 3. Relationship between allele / genotype frequency of rs2234693 locus and clinicopathological characteristics of bladder cancer
指标 等位基因 χ2值 P值 基因型 χ2值 P值 C T C/C C/T T/T 病理类型 0.633 0.729 2.746 0.601 颗粒型 1 1 0 2 0 上皮型 65 89 12 41 24 其他型 108 172 20 68 52 病理分级 4.306 0.230 7.276 0.296 Ⅰ 32 38 5 22 8 Ⅱ 42 48 8 26 11 Ⅲ 10 20 2 6 7 其他 91 157 17 57 50 临床分期 1.527 0.676 4.570 0.408 Ⅰ 49 61 8 33 14 Ⅱ 6 8 1 4 2 Ⅲ 1 1 0 1 0 其他 119 193 23 73 60 远处转移 1.616 0.656 6.389 0.381 MX 1 1 1 2 0 M0 55 75 8 39 18 M1 8 8 2 4 2 其他 108 178 21 66 56
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表 4 不同基因型病例组临床指标的比较(x ±s)
Table 4. Comparison of clinical indicators of different genotype case groups(x ±s)
指标 rs1801132 t值 P值 rs2234693 t值 P值 GG(n=52) GC+CC(n=168) CC(n=32) CT+TT(n=187) HGB(g/L) 143.05±20.52 133.96±21.90 2.374 0.019 142.00±38.18 135.92±21.80 0.390 0.697 RBC(×1012/L) 4.95±0.98 4.48±0.73 2.826 0.007 5.13±0.08 4.58±0.81 0.939 0.349 WBC(×109/L) 7.05±4.16 8.48±3.04 2.435 0.016 7.96±1.13 8.17±3.38 -0.086 0.932 NE% 58.47±16.54 63.69±13.22 2.106 0.037 75.45±0.92 62.39±14.16 1.301 0.195
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表 5 膀胱癌多因素条件Logistic回归分析模型分析结果
Table 5. Results of multivariate conditional Logistic regression analysis of bladder cancer
变量 OR(95% CI)值 P值 rs1801132 CC 1.000 GG 0.325(0.141~0.751) 0.009 GC 0.409(0.198~0.847) 0.016 rs2234693 TT 1.000 CC 0.745(0.293~1.896) 0.537 CT 0.437(0.217~0.882) 0.021 BMI(kg/m2) 18.5~ 1.000 <18.5 1.046(0.674~1.623) 0.843 ≥24 1.364(0.406~4.583) 0.615 饮酒 从不 1.000 饮酒 1.355(0.602~3.050) 0.464 吸烟 从不 1.000 吸烟 9.267(3.913~21.946) <0.001 运动 不达标a 1.000 达标 0.719(0.459~1.126) 0.150 憋尿 偶尔/从不 1.000 经常 3.500(1.424~8.601) 0.006 HGB(g/L)b 低值 1.000 正常/高值 0.333(0.158~0.705) 0.004 WBC(×109/L)c 正常/低值 1.000 高值 1.216(0.670~2.206) 0.521 心理压力 较/很紧张 1.000 轻松/不太紧张 0.177(0.096~0.327) < 0.001 注:a运动不达标定义为从不运动或者每周运动1~2 d,运动达 标定义为每天运动或者每周运动3~4 d;bHGB的正常参考区间为 130~175 g/L;cWBC的正常参考区间为(3.50~9.50)×109/L。
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表 6 不良生活习惯与危险基因型的叉生分析联合作用表
Table 6. Table of combined effects of bad living habits and bifurcation analysis of dangerous genotypes
指标 吸烟 rs1801132 rs2234693 OR值 95% CI值 OR值 95% CI值 年龄(岁) ≤60 否 1.000 1.000 >60 否 0.903 0.393~2.071 1.150 0.386~3.424 ≤60 是 1.086 0.399~2.957 1.348 0.529~3.436 >60 是 1.630 1.400~6.647 4.263 0.501~36.261 饮酒 否 否 1.000 1.000 是 否 1.483 1.341~1.799 1.083 0.421~2.785 否 是 1.907 1.352~2.335 1.075 0.380~3.042 是 是 2.416 1.264~7.593 2.200 0.252~19.241 BMI(kg/m2) 不超重 否 1.000 1.000 超重 否 0.838 0.314~2.234 0.860 0.252~2.581 不超重 是 1.991 1.347~2.392 1.039 0.320~3.372 超重 是 2.323 2.095~3.613 0.774 0.201~2.984
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