Cieślińska Anna, Sienkiewicz-Szłapka Edyta, Kostyra Elżbieta, Fiedorowicz Ewa, Snarska Jadwiga, Wroński Konrad, Tenderenda Michał, Jarmołowska Beata, Matysiewicz Michał
Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-719, Olsztyn, Poland.
Tumour Biol. 2015 Jun;36(6):4655-60. doi: 10.1007/s13277-015-3113-z. Epub 2015 Jan 25.
Structure-dependent μ-opioid receptor (MOR) activity is an important element in cancer opioid analgesic effectiveness. It is widely accepted that guanine (G) substitution for adenine (A) at OPRM1 gene sequence position 118 changes receptor glycosylation pattern. This is associated with decreased binding ability in both exogenous and endogenous opioids, resulting in increased human pain resistance. The endogenous opioid system's function in body homeostasis maintenance is considered mainly regulatory, so its participation in breast tumor formation and progression is identified herein. We examine the association of the most frequent MOR (A118G) gene polymorphism on breast cancer risk in a Northeastern Polish population by PCR-RFLP comparison of A and G allele frequency at OPRM1 gene A118G polymorphic site in breast cancer-diagnosed patients with healthy control group frequencies. Our results highlight a strong association between G allele presence at μ-opioid receptor A118G and increased breast cancer incidence (OR = 3.3, 95 % CI 2.2-5.0, p < 0.0001) and female gender (OR = 2.0, 95 % CI 1.4-2.9, p = 0.0004). Consequently, OPRM1 G allele presence at that site is a highly significant risk factor in breast cancer development.
结构依赖性μ-阿片受体(MOR)活性是癌症阿片类镇痛效果的重要因素。人们普遍认为,在OPRM1基因序列位置118处,鸟嘌呤(G)取代腺嘌呤(A)会改变受体糖基化模式。这与外源性和内源性阿片类药物的结合能力降低有关,导致人类疼痛耐受性增加。内源性阿片系统在维持身体内环境稳定中的作用主要被认为是调节性的,因此本文确定了其在乳腺肿瘤形成和进展中的参与情况。我们通过对乳腺癌确诊患者与健康对照组在OPRM1基因A118G多态性位点的A和G等位基因频率进行PCR-RFLP比较,研究了波兰东北部人群中最常见的MOR(A118G)基因多态性与乳腺癌风险的关联。我们的结果突出了μ-阿片受体A118G位点存在G等位基因与乳腺癌发病率增加(OR = 3.3,95% CI 2.2 - 5.0,p < 0.0001)以及女性性别(OR = 2.0,95% CI 1.4 - 2.9,p = 0.0004)之间的强烈关联。因此,该位点存在OPRM1 G等位基因是乳腺癌发展的一个高度显著的风险因素。