Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355, Poznan, Poland.
Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland.
Mol Biol Rep. 2021 Apr;48(4):3237-3244. doi: 10.1007/s11033-021-06328-7. Epub 2021 Apr 17.
On a global scale, breast cancer is the most common type of cancer in women, and it is still a growing problem. Therefore, new prognostic or diagnostic markers are required that would facilitate the assessment of patients or provide more efficient therapy, respectively. In these studies, we analyzed the contribution of LEP (2548G>A) and LEPR (109 Lys>Arg and 223Gln>Arg) genes polymorphisms to the risk of breast cancer development. The study involved 209 women aged 59.6 ± 11 years diagnosed with breast cancer and 202 healthy women aged 57.8 ± 8.2 years, who were blood donors. Polymorphism were evaluated by PCR-RFLP reaction followed by the verification of part of the samples by sequencing. The results of the study confirmed obesity as a significant breast cancer development risk factor in Polish women. However, no significant association between the studied polymorphisms and breast cancer risk or severity of the neoplastic disease was found. Interestingly, it was shown that wild type 223Gln>Gln leptin receptor (LEPR) was statistically more common in women with human epidermal growth factor receptor 2 negative (HER2-) than human epidermal groth factor receptor 2 positive (HER2+) breast cancer and wild type form of 2548G>A LEP was more common in women with progesterone receptor positive (PR+) than progesterone receptor negative (PR-) breast cancer. Studied polymorphisms of the LEP and LEPR genes do not increase breast cancer risk in the population of Polish women. However, they can affect PR an HER receptors expression and thus the severity of the disease. Noteworthy, this interesting correlation is being reported for the first time and might constitute an essential contribution to the identification of molecular mechanisms of carcinogenesis.
在全球范围内,乳腺癌是女性最常见的癌症类型,而且仍然是一个不断增长的问题。因此,需要新的预后或诊断标志物,分别有助于评估患者或提供更有效的治疗。在这些研究中,我们分析了 LEP(2548G>A)和 LEPR(109 Lys>Arg 和 223Gln>Arg)基因多态性对乳腺癌发展风险的贡献。该研究涉及 209 名年龄为 59.6±11 岁的被诊断患有乳腺癌的女性和 202 名年龄为 57.8±8.2 岁的健康献血女性。通过 PCR-RFLP 反应评估多态性,然后对部分样本进行测序验证。研究结果证实肥胖是波兰女性乳腺癌发展的一个重要危险因素。然而,研究中没有发现这些多态性与乳腺癌风险或肿瘤疾病严重程度之间存在显著关联。有趣的是,研究表明,野生型 223Gln>Gln 瘦素受体(LEPR)在人表皮生长因子受体 2 阴性(HER2-)乳腺癌女性中比人表皮生长因子受体 2 阳性(HER2+)乳腺癌女性更为常见,而野生型 2548G>A LEP 则更为常见于孕激素受体阳性(PR+)乳腺癌女性中。LEP 和 LEPR 基因的研究多态性不会增加波兰女性的乳腺癌风险。然而,它们可能会影响 PR 和 HER 受体的表达,从而影响疾病的严重程度。值得注意的是,这种有趣的相关性是首次报道的,可能对确定致癌作用的分子机制有重要贡献。