Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women

Abstract

OBJECTIVE: This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort. METHODS: This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction. RESULTS: The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group ( p =0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group ( p <0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p =0.813 and p =0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control ( p <0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group ( p <0.006). CONCLUSION: In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia

“…In three meta-analyses, significant associations of c.836 A > G (rs17576) MMP9 with breast cancer were not established [ 20 , 21 , 22 ]. Our data on the protective effect of the G allele (rs17576) on breast cancer in Caucasian women of Russia are consistent with the results of Resler et al, who studied white women of the Seattle metropolitan area (USA) [ 31 ], and contrast with the data obtained in Malaysian [ 29 ] and Brazilian [ 32 ] populations (according to their data, the G allele is risky).…”

“…Data from the literature on the association between c.836 A > G (rs17576) MMP9 and the disease are very contradictory. No associations of this locus with the disease were identified in two works [ 25 , 27 ] while opposite results (risk/protective value of polymorphism) were demonstrated in another three studies [ 29 , 31 , 32 ]. In three meta-analyses, significant associations of c.836 A > G (rs17576) MMP9 with breast cancer were not established [ 20 , 21 , 22 ].…”

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia

“…Due to their pleiotropism, polymorphisms of the MMP9 genes play a key role in multiple biological pathways and therefore have been implicated not only in peptic ulcer [ 13 , 73 , present study], but also in cardiovascular diseases [ 60 , 61 ] as well as a broad range of other disorders involving processes of synthesis and degradation of extracellular matrix: various cancers, including digestive [ 46 – 48 , 74 – 76 ], glaucoma [ 27 , 77 , 78 ], and others [ 79 – 82 ].…”

The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk

“…Convincing data have been obtained on the association of the production of a number of MMPs in the lesion with the induction of tumor growth and invasion, its more active metastasis, and poor survival in patients with BC [ 7 , 10 , 12 ]. However, at the same time, despite a fairly large number of association studies on the relationship of MMP gene polymorphism conducted at the moment (the PubMed/MEDLINE database contains materials from more than 50 such studies), the results of these studies are ambiguous and often do not agree with each other [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ], etc. For example, among four genetic studies of the association of c.259 T > C (rs1940475) MMP8 with BC, only one study established its association with the disease (BC metastasis) [ 13 ], whereas in three studies reliable data on the involvement of this polymorphism in BC formation were not obtained [ 14 , 15 , 16 ].…”

“…At the same time, it is important to emphasize that despite: (a) BMI involvement in BC formation [ 20 , 21 , 22 , 23 , 24 ], (b) a significant association of the MMP gene polymorphic loci with BC [ 13 , 17 , 18 , 19 ], and (c) correlations of MMP gene polymorphisms and the MMP protein level with obesity and obesity-related phenotypes (blood pressure, endothelial dysfunction, metabolic syndrome, etc.) [ 25 , 26 , 27 , 28 , 29 ], an integrated comprehensive genetic and bioinformatic analysis of the MMP gene association features with BC in obese/non-obese women has not been carried out.…”