外周血白细胞PDE4C基因甲基化及环境因素交互作用与乳腺癌发病的关系

doi:10.11904/j.issn.1002-3070.2019.03.008

实用肿瘤学杂志 ›› 2019, Vol. 33 ›› Issue (3): 233-238.doi: 10.11904/j.issn.1002-3070.2019.03.008

外周血白细胞PDE4C基因甲基化及环境因素交互作用与乳腺癌发病的关系

李烁,张楠楠,李亮亮,龙志平,尹慧慧,赵亚双,王帆

哈尔滨医科大学公共卫生学院(哈尔滨 150086)

收稿日期:2018-12-28 修回日期:2019-01-22 出版日期:2019-06-20 发布日期:2019-06-18
通讯作者: 王帆,E-mail:yifan.701@163.com
作者简介:李烁,女,(1993-),硕士研究生,从事乳腺癌基因甲基化的研究
基金资助:
国家自然科学基金(编号:81202262);中国博士后科学基金(编号:2013T60390);国家自然科学基金(编号:81172743);哈尔滨医科大学伍连德博士基金会(编号:WLD-QN1106);黑龙江省教育委员会(编号:12541340)

Relationship between PDE4C gene methylation in peripheral blood leukocytes,interaction of environmental factors and pathogenesis of breast cancer

LI Shuo,ZHANG Nannan,LI Liangliang,LONG Zhiping,YIN Huihui,ZHAO Yashuang,WANG Fan

Department of Epidemiology,Public Health College,Harbin Medical University,Harbin 150086,China

Received:2018-12-28 Revised:2019-01-22 Online:2019-06-20 Published:2019-06-18

摘要/Abstract

摘要： 目的探讨外周血白细胞中磷酸二酯酶4C(PDE4C)基因甲基化和环境因素的交互作用与乳腺癌发病的关系。方法采用病例对照研究,选择2010年10月—2014年12月纳入的402例乳腺癌病例和470例对照作为研究对象,使用特异性DNA甲基化修饰的定量PCR方法检测PDE4C基因的甲基化水平。应用叉生分析、多因素Logistic回归,分析基因甲基化水平及其和环境因素的交互作用与乳腺癌发病的关系。结果未发现PDE4C甲基化与乳腺癌的发病有显著关联。高频次/摄入量的粗粮、蔬菜、葱属性植物、禽肉、牛奶及经常运动可降低乳腺癌的发病风险;高频次/摄入量的猪肉,以及月经周期不规律、心理应激指数偏高可增加乳腺癌的发病风险。PDE4C高甲基化与食用葱属性植物大于3次/周有显著的联合作用(OR=0.373,95% CI:0.208~0.668,P=0.001)。结论 PDE4C基因高甲基化不是乳腺癌发病的独立危险因素,其与环境因素的联合作用影响乳腺癌的发病风险。

关键词: 乳腺癌, 甲基化, 磷酸二酯酶4C, 发病风险

Abstract: Objective The Objective of this study was to investigate the relationship between the methylation of phosphodiesterase 4C(PDE4C)gene in peripheral blood leukocytes,and its interaction with environmental factors and the pathogenesis of breast cancer.Methods A case-control study was conducted to select 402 cases of breast cancer and 470 cancer-free controls from October 2010 to December 2014.The specific DNA methylation-modified quantitative PCR method was used to detect the methylation of PDE4C gene.The use of crossover analysis and multivariate logistic regression was used to analyze the relationship between the level of gene methylation and its interaction with environmental factors and the pathogenesis of breast cancer.Results PDE4C methylation was not found to be significantly associated with the onset of breast cancer.High-frequency/high-intake of whole grains,vegetables,onion-based plants,poultry,milk,and regular exercise could reduce the risk of breast cancer;high-frequency/high-intake of pork,irregular menstrual cycle,and a high psychological stress index could increase the risk of breast cancer.PDE4C hypermethylation had a significant combining effect with edible onion-producing plants greater than 3 times/week,with an OR of 0.373(95% CI:0.208~0.668,P=0.001).Conclusion Hypermethylation of PDE4C is not an independent risk factor for breast cancer,and its combination with environmental factors affects the risk of breast cancer.

Key words: Breast cancer, Methylation, Phosphodiesterase 4C, Risk

中图分类号:

R739.9

李烁,张楠楠,李亮亮,龙志平,尹慧慧,赵亚双,王帆. 外周血白细胞PDE4C基因甲基化及环境因素交互作用与乳腺癌发病的关系[J]. 实用肿瘤学杂志, 2019, 33(3): 233-238.

LI Shuo,ZHANG Nannan,LI Liangliang,LONG Zhiping,YIN Huihui,ZHAO Yashuang,WANG Fan. Relationship between PDE4C gene methylation in peripheral blood leukocytes,interaction of environmental factors and pathogenesis of breast cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(3): 233-238.

参考文献 1

Siegel RL,Miller KD,Jemal A.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.2 Stempak JM,Sohn KJ,Chiang EP,et al.Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model[J].Carcinogenesis,2005,26(5):981-990.3 Li H,Zuo J,Tang W.Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases[J].Front Pharmacol,2018,17(9):1048.4 Bao Z,Feng Y,Wang H,et al.Integrated analysis using methylation and gene expression microarrays reveals PDE4C as a prognostic biomarker in human glioma[J].Oncol Rep,2014,32(1):250-260.5 Ostrow KL,Hoque MO,Loyo M,et al.Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR[J].Clin Cancer Res,2010,16(13):3463-3472.6 Krejcova P,Kucerova P,Stafford GI,et al.Antiinflammatory and neurological activity of pyrithione and related sulfur-containing pyridine N-oxides from Persian shallot(Allium stipitatum)[J].J Ethnopharmacol,2014,154(1):176-182.7 Ersin F,Bahar Z.Effect of health belief model and health promotion model on breast cancer early diagnosis behavior:a systematic review[J].Asian Pac J Cancer Prev,2011,12(10):2555-2562.8 Choi JY,James SR,Link PA,et al.Association between global DNA hypomethylation in leukocytes and risk of breast cancer[J].Carcinogenesis,2009,30(11):1889-1897.9 McGuire S.World cancer report 2014.geneva,switzerland:world health organization,international agency for research on cancer,WHO press,2015[J].Adv Nutr,2016,7(2):418-419.10 Hanf V,Gonder U.Nutrition and primary prevention of breast cancer:foods,nutrients and breast cancer risk[J].Eur J Obstet Gynecol Reprod Biol,2005,123(2):139-149.11 Wiseman M.The second world cancer research fund/american institute for cancer research expert report.food,nutrition,physical activity,and the prevention of cancer:a global perspective[J].Proc Nutr Soc,2008,67(3):253-256.12 郑伟,许守平,庞达.ERα基因单核苷酸多态性与乳腺癌应用芳香化酶抑制剂引发骨丢失的相关性研究[J].实用肿瘤学杂志,2018,32(1):14-18.13 Turati F,Guercio V,Pelucchi C,et al.Colorectal cancer and adenomatous polyps in relation to allium vegetables intake:a meta-analysis of observational studies[J].Mol Nutr Food Res,2014,58(9):1907-1914.14 Nicastro HL,Ross SA,Milner JA.Garlic and onions:their cancer prevention properties[J].Cancer Prev Res(Phila),2015,8(3):181-189.

[1]	王晓雅,肖斌,廖扬,唐荣芝,孙朝晖,李林海. CXCR家族蛋白在不同乳腺癌亚型中的表达及临床预后分析[J]. 实用肿瘤学杂志, 2019, 33(3): 206-210.
[2]	李嘉琪,栾瑾微,张,玉,李香兰. 763例三阴性乳腺癌临床病理特征及复发、转移影响因素分析[J]. 实用肿瘤学杂志, 2019, 33(3): 244-249.
[3]	陈艳波, 孔德嘉, 张金锋, 马志刚. 乳腺癌患者CYP2D6基因多态性与他莫昔芬代谢相关性研究[J]. 实用肿瘤学杂志, 2019, 33(2): 110-114.
[4]	孙江宏, 郝明珠, 姜丹, 国飞, 李晓梅. 乳腺炎、良性增生及乳腺癌FFDM鉴别诊断思路[J]. 实用肿瘤学杂志, 2019, 33(2): 139-141.
[5]	马志杰, 王帆, 赵亚双. 乳腺癌化疗患者生存质量及影响因素分析[J]. 实用肿瘤学杂志, 2019, 33(2): 149-154.
[6]	白玉贤, 马仲娟, 苏颖玲, 慕安国, 谢蕊. 胃癌患者FHIT、hMLH1、p16、RAR-beta、Reprimo和TIMP3基因的甲基化研究[J]. 实用肿瘤学杂志, 2019, 33(1): 8-13.
[7]	马质莹, 尚乃舰, 蔡妙田, 沈阳, 姜智允. 孕激素及雌激素受体阳性乳腺癌HER-2受体与钼靶影像学特征及临床病理学特征的相关性分析[J]. 实用肿瘤学杂志, 2019, 33(1): 47-51.
[8]	何煦, 叶尚勉, 董丹丹, 李科. HLA-G在乳腺癌中的表达及意义[J]. 实用肿瘤学杂志, 2018, 32(5): 410-414.
[9]	林荣杰, 尹航, 周云峰. ON123300对ER阳性人乳腺癌MCF-7细胞的影响及机制研究[J]. 实用肿瘤学杂志, 2018, 32(3): 193-197.
[10]	李林(综述), 李志高(审校). 二甲双胍与不同分子亚型乳腺癌的关系[J]. 实用肿瘤学杂志, 2018, 32(3): 267-270.
[11]	郑伟, 许守平, 庞达. 长链非编码RNA Linc00152在泛癌中表达、预后及功能研究[J]. 实用肿瘤学杂志, 2018, 32(1): 7-13.
[12]	殷玉莲, 张卫红, 周悦, 叶媚娜, 陈红风. ERα基因单核苷酸多态性与乳腺癌应用芳香化酶抑制剂引发骨丢失的相关性研究[J]. 实用肿瘤学杂志, 2018, 32(1): 14-18.
[13]	黎玉娇, 尚乃舰. 影像学评估乳腺癌新辅助化疗反应的研究进展[J]. 实用肿瘤学杂志, 2018, 32(1): 63-67.
[14]	陈琢, 孔艺然. 沉默UHRF1对乳腺癌细胞增殖和转移的影响[J]. 实用肿瘤学杂志, 2017, 31(6): 512-518.
[15]	李红阳, 孙亮, 姜醒, 苑光军, 刘艳. 蝙蝠葛碱在人乳腺癌MCF-7细胞对5氟尿嘧啶敏感性的研究[J]. 实用肿瘤学杂志, 2017, 31(5): 385-389.

外周血白细胞PDE4C基因甲基化及环境因素交互作用与乳腺癌发病的关系

Relationship between PDE4C gene methylation in peripheral blood leukocytes,interaction of environmental factors and pathogenesis of breast cancer

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 1

相关文章 15

编辑推荐

Metrics

本文评价