Institute of Biotechnology & Genetic Engineering (Health Division), The University of Agriculture Peshawar, Peshawar, 25130, Pakistan.
School of Mechanical and Manufacturing Engineering, NUST, Islamabad, 44000, Pakistan.
Mol Biol Rep. 2024 Oct 3;51(1):1034. doi: 10.1007/s11033-024-09968-7.
Single Nucleotide polymorphisms (SNPs) in MMP8 and MMP9 have been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check MMP8 (rs11225395) and MMP9 (rs3787268) polymorphism with breast cancer risk in the selected population.
This study, consisting of 300 breast cancer patients and 168 gender and age-matched healthy controls was subjected to confirm MMP8 and MMP9 polymorphisms. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using the T-ARMS-PCR protocol.
Based on our study results, significant associations were observed between the MMP8 rs11225395 risk allele (G) and increased breast cancer risk, with the G allele frequency higher in patients (65%) compared to controls (51%) (OR = 1.752, 95% CI = 1.423-3.662, p = 0.002). Genotypes GG (OR = 4.218, p = 0.005) and AG (OR = 7.286, p = 0.0001) of MMP8 rs11225395 were also significantly associated with elevated breast cancer risk. Similarly, MMP9 rs3787268 exhibited a higher frequency of the risk allele (A) in breast cancer cases (81%) compared to controls (41%), correlating strongly with increased risk (OR = 6.320, p = 0.0001). Genotypes AA (OR = 14.500, p = 0.0001) and AG (OR = 2.429, p = 0.077) of MMP9 rs3787268 containing the risk allele showed significant associations with heightened breast cancer risk. Subgroup analyses based on age, disease progression, tumor size, and grade revealed noteworthy associations for both MMP8 rs11225395 and MMP9 rs3787268. MMP8 rs11225395 genotypes displayed significant correlations with age (p = 0.066), disease progression (p = 0.0001), larger tumor size (p = 0.005), and higher tumor grade (p = 0.006). Similarly, MMP9 rs3787268 genotypes were significantly associated with age (p = 0.001), disease progression (p = 0.010), larger tumor size (p = 0.018), and higher tumor grade (p = 0.037). Logistic regression analyses further underscored these genetic variants' potential role as biomarkers in breast cancer, particularly in relation to specific hormone receptor statuses such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) positivity.
The results revealed significant associations between the mutant alleles and genotypes of MMP8 (rs11225395) and MMP9 (rs3787268) with increased breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.
基质金属蛋白酶 8（MMP8）和基质金属蛋白酶 9（MMP9）中的单核苷酸多态性（SNP）与不同种族的乳腺癌风险广泛相关，但结果不一致。迄今为止，在巴基斯坦开伯尔-普赫图赫瓦的普什图人群中还没有进行过这样的研究。因此，本研究旨在检查 MMP8（rs11225395）和 MMP9（rs3787268）多态性与所选人群的乳腺癌风险的关系。
本研究包括 300 名乳腺癌患者和 168 名性别和年龄匹配的健康对照者，进行 MMP8 和 MMP9 多态性确认。从所有参与者中采集临床病理数据和血液样本。使用 T-ARMS-PCR 方案提取 DNA 并确认 SNP。
根据我们的研究结果，MMP8 rs11225395 风险等位基因（G）与乳腺癌风险增加之间存在显著关联，患者中 G 等位基因频率（65%）高于对照组（51%）（OR=1.752，95%CI=1.423-3.662，p=0.002）。MMP8 rs11225395 的 GG（OR=4.218，p=0.005）和 AG（OR=7.286，p=0.0001）基因型也与乳腺癌风险增加显著相关。同样，MMP9 rs3787268 在乳腺癌病例中表现出较高的风险等位基因（A）频率（81%），与风险增加密切相关（OR=6.320，p=0.0001）。携带风险等位基因的 MMP9 rs3787268 的 AA（OR=14.500，p=0.0001）和 AG（OR=2.429，p=0.077）基因型与乳腺癌风险增加也存在显著关联。基于年龄、疾病进展、肿瘤大小和分级的亚组分析显示，MMP8 rs11225395 和 MMP9 rs3787268 均存在显著相关性。MMP8 rs11225395 基因型与年龄（p=0.066）、疾病进展（p=0.0001）、肿瘤较大（p=0.005）和肿瘤分级较高（p=0.006）显著相关。同样，MMP9 rs3787268 基因型与年龄（p=0.001）、疾病进展（p=0.010）、肿瘤较大（p=0.018）和肿瘤分级较高（p=0.037）显著相关。逻辑回归分析进一步强调了这些遗传变异作为生物标志物在乳腺癌中的潜在作用，特别是与特定的激素受体状态如雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体 2（HER2）阳性相关。
结果显示，MMP8（rs11225395）和 MMP9（rs3787268）的突变等位基因和基因型与巴基斯坦开伯尔-普赫图赫瓦的普什图人群乳腺癌风险增加之间存在显著关联。然而，需要在更大的数据集上进行更多的研究，以确认所选 SNP 以及与乳腺癌风险相关的其他 SNP 以及选定和其他相关基因中的其他 SNP。
