中国医科大学学报  2018, Vol. 47 Issue (12): 1057-1062

文章信息

吴鑫, 石晶, 李智, 李贺明, 曲秀娟, 刘云鹏, 张凌云
WU Xin, SHI Jing, LI zhi, LI Heming, QU Xiujuan, LIU Yunpeng, ZHANG Lingyun
中国东北地区人群饮用绿茶与结直肠癌发病关系的病例对照研究
Green Tea Consumption and Colorectal Cancer Risk: a Case-Control Study in Northeast China
中国医科大学学报, 2018, 47(12): 1057-1062
Journal of China Medical University, 2018, 47(12): 1057-1062

文章历史

收稿日期:2018-04-02
网络出版时间:2018-11-29 14:25
中国东北地区人群饮用绿茶与结直肠癌发病关系的病例对照研究
吴鑫1 , 石晶1 , 李智1 , 李贺明2 , 曲秀娟1 , 刘云鹏1 , 张凌云1     
1. 中国医科大学附属第一医院肿瘤内科, 沈阳 110001;
2. 大连大学附属中山医院肿瘤科, 辽宁 大连 116001
摘要目的 探讨饮用绿茶与结直肠癌(CRC)发病的关系。方法 采用病例对照研究,收集2009年6月至2011年11月在中国医科大学附属第一医院确诊的新发CRC病例763例,及同期内经年龄、性别及居住地区1:1匹配的体检人员763例。应用非条件logistic回归计算饮绿茶及相关变量与CRC发病风险的调整OR值及95%CI结果 饮绿茶可降低结直肠癌的发病风险(aOR=0.40,95%CI:0.30~0.52)。饮茶杯数的增加、饮茶年限的延长、干茶叶消费量的增多均与CRC的发病风险降低有关(P < 0.05)。饮茶>1杯/d者,CRC发病风险降低65%(aOR=0.35,95%CI:0.23~0.52);饮绿茶年限1~10年与干茶叶消费量500~1 000 g/年者,CRC发病风险分别降低61%(aOR=0.39,95%CI:0.28~0.55)和71%(aOR=0.29,95%CI:0.18~0.49)。发病部位和性别的亚组分析表明,饮绿茶可以降低近端结肠癌、远端结肠癌、直肠癌的发病风险,并降低男性、女性CRC的发病风险。结论 饮绿茶是CRC发病的保护因素。
关键词绿茶    结直肠癌    病例对照研究    
Green Tea Consumption and Colorectal Cancer Risk: a Case-Control Study in Northeast China
1. Department of Medical Oncology, The First Hospital, China Medical University, Shenyang 110001, China;
2. Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
Abstract: Objective To evaluate the association between green tea consumption and colorectal cancer (CRC) risk in northeast China. Methods This was a matched case-control study involving 763 patients with CRC that had been confirmed by pathological diagnosis, as well as 763 healthy controls that were matched in terms of age frequency, sex and location. All participants were recruited at the China Medical University 1st Hospital between June 2009 and November 2011. Unconditional logistic regression was used to calculate adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CI) to assess the association between green tea consumption and CRC. Results Green tea consumption was associated with a decreased risk of CRC. Moreover, greater daily quantity, longer duration of tea drinking, and greater consumption of dry tea were all related to decreased risk (P < 0.05). In participants who drank more than one cup of green tea per day, the risk of CRC was reduced by 65% (aOR=0.35, 95% CI:0.23-0.52). In those who drank green tea for 1 to 10 years, the risk of CRC was reduced by 61% (aOR=0.39, 95% CI:0.28-0.55), while in those who consumed 500 to 1 000 g of dry tea per year, it was reduced by 71% (aOR=0.29, 95% CI:0.18-0.49). When CRC was stratified in terms of subsite, green tea drinking was inversely associated with the risk of proximal colon cancer, distal colon cancer, and rectal cancer. When the participants were stratified by sex, green tea consumption was found to reduce CRC risk in both men and women. Conclusion Green tea drinking is protective against CRC.
Keywords: green tea    colorectal cancer    case-control study    

结直肠癌(colorectal cancer,CRC)发病率居世界第三位,且近年来中国CRC发病率呈显著上升趋势[1]。结直肠癌发病与遗传、环境及饮食因素密切相关[2]。其中,饮食因素是结直肠癌发病过程中最易被调控的因素。近年来流行病学研究[3-5]证实,饮绿茶可降低多种癌症(胃癌、前列腺癌等)的发病率。但饮绿茶是否降低CRC的发病率尚存在争议[6-8]。本研究在中国东北地区开展病例对照研究,探讨绿茶与CRC发病风险之间的关系,为CRC的一级预防提供基础及依据。

1 材料与方法 1.1 一般资料

研究对象来自2009年6月至2011年11月中国医科大学附属第一医院确诊的新发CRC病例(病例组)及同期内于该医院进行体检的人员(对照组),且均居住于辽宁省,年龄 > 18岁。病例组与对照组按5岁年龄组、性别和居住地区(城市/农村)三方面进行1:1配对。排除标准:(1)精神病;(2)糖尿病、慢性消化系统疾病及免疫系统疾病;(3)心脑血管疾病;(4)结直肠良性病变。本研究已通过中国医科大学附属第一医院伦理委员会批准。所有研究对象均签署知情同意书。

1.2 方法

1.2.1 调查方法

采集研究对象1年前的相关饮食信息。所有研究对象均由相应专业培训的调查人员采用结构化的调查问卷,以面对面的方式进行问卷调查,每次调查时间控制在30~45 min。

1.2.2 调查内容

一般人口学特征,如体质量指数(body mass index,BMI)、收入及文化程度等;家族史;个人生活习惯,如吸烟、饮酒史等;红肉、蔬菜及水果等99项常见食物的摄入频次及每餐数量;茶叶的问卷内容包括是否规律饮茶、平均饮茶频率、饮茶年限和干茶叶平均消费量。

1.2.3 调整因素

根据既往相似文献,筛选出13个调整变量。分类变量为BMI(kg/m2)、家族史、吸烟史及教育程度;连续变量为酒精、肉类、蔬菜、水果、总能量、纤维、脂肪、钙及维生素C等的摄入量。根据张敏等[9]报道中的换算公式,将酒类变量换算成酒精(kg/年)。

1.3 统计学分析

应用SPSS 19.0进行数据的录入与资料分析。2组的一般情况和饮食因素方面的差异采用χ2检验(分类变量)和t检验(连续变量)计算;饮绿茶相关变量采用非条件logistic回归模型进行单因素、多因素回归分析,并计算OR值和95%CIP < 0.05为差异有统计学意义。

2 结果 2.1 一般情况(表 1
表 1 病例组和对照组人口学特征(n = 763) Tab.1 Comparison of main characteristics between the case and control groups (n = 763)
Variables Cases group Control group χ2/t P
BMI [kg/m2n(%)]     2.899 0.235
  ≤25 499(65.4) 528(69.2)    
   > 25-30 233(30.5) 203(26.6)    
   > 30 31(4.1) 32(4.2)    
Family history of colorectal cancer [n(%)]     23.903 < 0.001
  No 721(94.5) 755(99.0)    
  Yes 42(5.5) 8(1.0)    
Education level [n(%)]     0.097 0.755
  Below high school 446(58.5) 452(59.2)    
  High school and above 317(41.5) 311(40.8)    
Tobacco smoking [n(%)]     13.611 < 0.001
  No 457(59.9) 526(68.9)    
  Yes 306(40.1) 237(31.1)    
Alcohol drinking(g/year) 6.33±16.72 2.42±8.28 -5.794 < 0.001
Red meat consumption(kg/year) 27.95±27.55 16.59±15.94 -9.858 < 0.001
Vegetable consumption(kg/year) 106.02±70.49 122.14±60.62 4.789 < 0.001
Fruit consumption(kg/year) 82.81±83.15 120.50±112.66 7.433 < 0.001
Total energy(kkal) 863.09±396.45 809.96±331.97 -2.838 0.005
Fiber intake(kg/year) 2.99±2.83 2.94±2.82 -0.419 0.675
Calcium intake(g/year) 147.72±161.49 149.89±140.53 0.281 0.281
Fat intake(kg/year) 13.22±9.89 9.97±7.86 -7.100 < 0.001
Vitamin C intake(g/year) 45.64±37.89 59.89±44.84 6.706 < 0.001

2组在BMI、教育程度、纤维及钙摄入方面均衡可比。在家族史、吸烟史、饮酒、红肉、总能量、脂肪、蔬菜、水果、钙及维生素C的摄入等方面分布,差异有统计学意义(P < 0.05)。

2.2 绿茶与结直肠癌的关系
表 2 绿茶与结直肠癌关系的非条件logistic回归分析(n = 763) Tab.2 Univariate and multivariate logistic regression of the association between green tea consumption and colorectal cancer risk (n = 763)
Variables Case group [n(%)] Control group [n(%)] OR(95%CI aOR(95%CIa
Tea consumption        
  No 592(77.6) 504(66.1) 1 1
  Yes 171(22.4) 259(33.9) 0.56(0.45-0.70) 0.40(0.30-0.52)
  P     < 0.001 < 0.001
Quantity of tea consumed        
  No 592(77.6) 504(66.1) 1 1
   < 1 cup/d 70(9.2) 87(11.4) 0.68(0.48-0.95) 0.45(0.30-0.67)
  1 cup/d 43(5.6) 78(10.2) 0.46(0.31-0.69) 0.39(0.25-0.61)
   > 1 cup/d 58(7.6) 94(12.3) 0.52(0.37-0.74) 0.35(0.23-0.52)
  P     < 0.001 < 0.001
Duration of tea consumption(year)        
  No 592(77.6) 504(66.1) 1 1
  1-10 90(11.8) 140(18.3) 0.55(0.41-0.73) 0.39(0.28-0.55)
  s > 10 81(10.6) 119(15.6) 0.58(0.43-0.79) 0.41(0.29-0.58)
  P     < 0.001 < 0.001
Amount of dry green tea consumed(g/year)        
  No 592(77.6) 504(66.1) 1 1
  ≤500 103(13.5) 148(19.4) 0.59(0.45-0.78) 0.44(0.32-0.61)
   > 500-1 000 31(4.1) 60(7.9) 0.44(0.28-0.70) 0.29(0.18-0.49)
   > 1 000 37(4.8) 51(6.6) 0.62(0.40-0.96) 0.40(0.24-0.65)
  P     < 0.001 < 0.001
a,adjustment for BMI,family history of colorectal cancer,education level,tobacco smoking,alcohol drinking,red meat,vegetables,fruits consumption,total energy,fibre,calcium,fat,vitamin C intake.

绿茶与CRC关系的非条件logistic回归结果显示,病例组饮用绿茶者显著少于对照组(22.4% vs 33.9%;P < 0.001);与不饮绿茶者相比,饮绿茶者发生CRC的风险显著降低,调整OR(aOR)=0.40,95%CI:0.30~0.51。与不饮用绿茶者相比,饮茶杯数越多,CRC的发病风险越低(P < 0.001),其中 > 1杯/d者CRC发病风险最低(aOR = 0.35,95%CI:0.23~0.52)。另外,随着饮绿茶年限增长和干茶叶的年平均消费量的增加,CRC的发病风险均显著降低(P < 0.001)。饮绿茶时间在1~10年者aOR值为0.39(95%CI:0.28~0.55),干茶叶的年平均消费量500~1 000 g/年者保护作用最为明显,其aOR = 0.29(95%CI:0.18~0.49)。

2.3 结直肠癌发病部位分层分析

按发病部位进行分层分析显示,绿茶使近端结肠癌、远端结肠癌、直肠癌发病风险分别降低55%、64%和63%(P < 0.05)。饮茶频率、饮茶年限、干茶叶消费量等因素,均与不同部位CRC的发病风险有关,见表 3

表 3 绿茶与近端结肠癌、远端结肠癌、直肠癌关系的非条件logistic回归分析 Tab.3 Univariate and multivariate logistic regression of the association between green tea consumption and the risk of proximal colon cancer, distal colon cancer, and rectal cancer
Variables Proximal colon cancer Distal colon cancer Rectal cancer
Case/control OR(95%CI aOR(95%CIa Case/control OR(95%CI aOR(95%CIa Case/control OR(95%CI aOR(95%CIa
Tea consumption                  
  No 146/121 1 1 141/120 1 1 305/263 1 1
  Yes 42/67 0.50(0.32-0.79) 0.45(0.27-0.75) 50/71 0.59(0.38-0.92) 0.36(0.21-0.62) 79/121 0.56(0.40-0.78) 0.37(0.25-0.56)
  P   0.030 0.020   0.020 < 0.001   0.001 < 0.001
Quantity of tea consumed                  
  No 146/121 1 1 141/120 1 1 305/263 1 1
   < 1 cup/d 15/22 0.56(0.28-1.13) 0.47(0.21-1.06) 22/24 0.78(0.41-1.46) 0.47(0.22-1.03) 33/41 0.69(0.42-1.13) 0.40(0.22-0.72)
  1 cup/d 13/17 0.63(0.29-1.35) 0.57(0.24-1.33) 12/24 0.42(0.20-0.88) 0.30(0.13-0.69) 18/37 0.41(0.23-0.75) 0.39(0.20-0.75)
   > 1 cup/d 14/28 0.41(0.20-0.82) 0.38(0.18-0.84) 16/23 0.59(0.29-1.17) 0.34(0.15-0.74) 28/43 0.56(0.33-0.92) 0.34(0.18-0.62)
  P   0.030 0.005   0.010 0.001   0.001 < 0.001
Duration of tea consumption(year)                  
  No 146/121 1 1 141/120 1 1 305/263 1 1
  1-10 24/31 0.64(0.35-1.15) 0.51(0.26-0.99) 23/43 0.45(0.26-0.79) 0.28(0.14-0.55) 43/66 0.56(0.37-0.85) 0.36(0.22-0.60)
  s > 10 18/36 0.41(0.22-0.76) 0.40(0.20-0.80) 27/28 0.82(0.45-1.46) 0.48(0.25-0.95) 36/55 0.56(0.35-0.88) 0.39(0.22-0.68)
  P   0.010 0.006   0.270 0.010   0.004 < 0.001
Amount of dry green tea consumed(g/year)                  
  No 146/121 1 1 141/120 1 1 305/263 1 1
  ≤500 27/38 0.58(0.34-1.02) 0.49(0.26-0.91) 30/43 0.59(0.35-1.00) 0.40(0.21-0.75) 46/67 0.59(0.39-0.89) 0.40(0.25-0.66)
   > 500-1 000 8/11 0.60(0.23-1.54) 0.72(0.26-1.95) 9/18 0.42(0.18-0.98) 0.26(0.10-0.68) 14/31 0.38(0.20-0.74) 0.19(0.08-0.44)
   > 1 000 7/18 0.32(0.13-0.79) 0.24(0.08-0.67) 11/10 0.93(0.38-2.28) 0.41(0.14-1.21) 19/23 0.71(0.38-1.33) 0.54(0.25-1.13)
  P   0.020 0.005   0.170 0.003   0.010 0.001
a,adjustment for BMI,family history of colorectal cancer,education level,tobacco smoking,alcohol drinking,red meat,vegetables,fruits consumption,total energy,fibre,calcium,fat,vitamin C intake.

2.4 结直肠癌性别分层分析

按性别进行分层分析显示,与不饮绿茶者相比,男性、女性中饮绿茶者发生CRC的风险分别降低57%和61%(P < 0.05)。饮茶杯数,饮绿茶时间、干茶叶的年平均消费量均与CRC发病风险有关,见表 45

表 4 男性中绿茶与结直肠癌关系的非条件logistic回归分析(n = 434) Tab.4 Univariate and multivariate logistic regression of the association between green tea consumption and colorectal cancer risk in men (n = 434)
Variables Case group [n(%)] Control group [n(%)] OR(95%CI aOR(95%CIa
Tea consumption        
  No 294(67.7) 235(54.1) 1 1
  Yes 140(32.3) 199(45.9) 0.56(0.43-0.74) 0.43(0.31-0.60)
  P     < 0.001 < 0.001
Quantity of tea consumed        
  No 294(67.7) 235(54.1) 1 1
   < 1 cup/d 55(12.7) 62(14.3) 0.70(0.47-1.05) 0.53(0.32-0.84)
  1 cup/d 33(7.6) 63(14.5) 0.41(0.26-0.66) 0.36(0.22-0.63)
   > 1 cup/d 52(12.0) 74(17.1) 0.56(0.37-0.83) 0.39(0.25-0.63)
  sP     < 0.001 < 0.001
Duration of tea consumption(year)        
  No 294(67.7) 235(54.1) 1 1
  1-10 72(16.6) 99(22.8) 0.58(0.41-0.82) 0.45(0.29-0.67)
   > 10 68(15.7) 100(23.1) 0.54(0.38-0.77) 0.40(0.28-0.64)
  P     < 0.001 < 0.001
Amount of dry green tea consumed(g/year)        
  No 294(67.7) 235(54.1) 1 1
  ≤500 80(18.5) 102(23.5) 0.63(0.45-0.88) 0.54(0.36-0.80)
   > 500-1 000 27(6.2) 52(12.0) 0.42(0.25-0.68) 0.27(0.15-0.51)
   > 1 000 33(7.6) 45(10.4) 0.59(0.36-0.95) 0.38(0.22-0.66)
  P     < 0.001 < 0.001
a,adjustment for BMI,family history of colorectal cancer,education level,tobacco smoking,alcohol drinking,red meat,vegetables,fruits consumption,total energy,fibre,calcium,fat,vitamin C intake.

表 5 女性中绿茶与结直肠癌关系的非条件logistic回归分析(n = 329) Tab.5 Univariate and multivariate logistic regression of the association between green tea consumption and colorectal cancer risk in women (n = 329)
Variables Case group [n(%)] Control group [n(%)] OR(95%CI aOR(95%CIa
Tea consumption        
  No 298(90.6) 269(81.5) 1 1
  Yes 31(9.4) 60(18.5) 0.46(0.29-0.73) 0.39(0.24-0.66)
  P     < 0.001 < 0.001
Quantity of tea consumed        
  No 298(90.6) 269(81.5) 1 1
   < 1 cup/d 15(4.6) 25(7.7) 0.54(0.28-1.04) 0.39(0.18-0.83)
  1 cup/d 10(3.0) 15(4.7) 0.62(0.26-1.36) 0.74(0.30-1.80)
   > 1 cup/d 6(1.8) 20(6.1) 0.27(0.10-0.68) 0.22(0.08-0.59)
  P     0.001 < 0.001
Duration of tea consumption        
  No 298(90.6) 269(81.5) 1 1
  1-10 years 18(5.4) 41(12.6) 0.40(0.22-0.71) 0.34(0.18-0.64)
   > 10 years 13(4.0) 19(5.9) 0.62(0.30-1.28) 0.53(0.24-1.16)
  P     0.020 0.010
Amount of dry green tea consumed        
  No 298(90.6) 269(81.5) 1 1
  ≤500 g/year 23(7.0) 46(14.1) 0.45(0.27-0.76) 0.36(0.20-0.65)
   > 500-1 000 g/year 4(1.2) 8(2.5) 0.45(0.13-1.52) 0.43(0.12-1.16)
   > 1 000 g/year 4(1.2) 6(1.9) 0.60(0.17-2.16) 0.71(0.18-2.79)
  P     0.020 0.030
a,adjustment for BMI,family history of colorectal cancer,education level,tobacco smoking,alcohol drinking,red meat,vegetables,fruits consumption,total energy,fibre,calcium,fat,vitamin C intake.

3 讨论

本病例对照研究显示,饮绿茶可显著降低CRC的发病风险。大量研究[10-12]表明,绿茶中的多酚类物质具有抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡,抗肿瘤侵袭和血管生成等作用。

本研究结果显示,规律饮绿茶、饮茶杯数增加均可显著降低CRC的发病风险,这与之前的流行病学研究[6, 8, 13]结论相一致。上海的1项队列研究[6]显示,规律饮用绿茶的女性,CRC的发病风险降低37%。但也有队列研究及Meta分析[7, 14]显示,绿茶对CRC并无保护作用。在新加坡华人的1项研究[15]中,饮用绿茶频率≥1次/月者,男性CRC的风险增加30%。研究结论不一致的原因可能是多方面的。首先,各研究在茶叶摄入量的评估单位上不尽相同,如杯/d、mL/d、次/d,而衡量单位的多样性使得各研究在评估茶叶消费量上存在差异。本研究选用最常用的杯/d作为衡量单位并标明茶杯容量(350~400 mL茶杯),与其他大部分研究中常用的衡量单位保持一致,增加研究结果的可比性。其次,部分研究[16]可能存在对混杂因素如蔬菜、水果等控制不佳的情况。而大量研究[17-19]证实,蔬菜、水果可显著降低CRC的发病风险。本研究把影响CRC发病的其他因素如蔬菜、水果、红肉的摄入量等纳入调整因素,有效地控制混杂因素的影响。本研究针对中国东北地区人群探讨绿茶与CRC发病风险之间的关系,对中国东北地区人群选择健康的生活方式提供可靠依据。

本研究显示,干茶叶的消费量增加、饮茶年限与CRC发病率降低有关。与本研究相似,上海1项队列研究[6]显示,绿茶的消费量和饮茶年限均与CRC发病风险存在显著的剂量反应关系,消费干茶叶的量每增加1.67 g/d和饮绿茶年限每增加5年,CRC的风险均降低10%。在新加坡华人的研究[15]中发现,与不饮绿茶者相比,饮绿茶≥1年的男性CRC的发病风险降低49%。但是,本研究显示,饮茶在 > 10年者及 > 1 000 g/年者aOR均略高于≤10年和≤1 000 g/年者,其可能是本研究规律饮茶人数占比较低、以及 > 10及 > 1 000 g/年者2组人数较少的原因。本研究中总体饮茶者在病例组和对照组中分别占22.4%和34.1%,尤其在女性 > 1 000 g/年组中饮绿茶者仅占有1.2%和1.9%,明显低于上海的研究人群饮绿茶者的比例。茶水中的生物活性含量可能受多种因素的影响,尤其是干茶叶的用量。本研究选用干茶叶的使用量作为衡量单位之一,增加了研究结果的准确性。

综上所述,饮绿茶可显著降低CRC的发病风险。本研究属于病例对照研究,可能存在回忆偏倚和选择偏倚。因此,本研究结果仍需要大规模的队列研究进一步加以验证。

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