Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women

Habel, Azza; Ghali, Rabeb M; Daldoul, Amira; Hadj-Ahmed, Mariem; Mokrani, Amina; Zaied, Sonia; Hechiche, M; Rahal, Khaled; Yacoubi-Loueslati, Besma; Almawi, Wassim Y.

doi:10.1177/1010428319845749

Cited by 21 publications

(21 citation statements)

References 36 publications

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“…Leptin and LEPR Q223R (rs1137101) were identified as risk factors for breast cancer in Egyptian and Nigerian women ( 139 – 141 ) while leptin alone was notably reported as a key driver of breast cancer progression through the induction of JAK/STAT3 , ERK1/2 , and estrogen pathways in obese Egyptian women ( 142 ). Furthermore, variants of VEGF and MMPs , which induce the upregulation of these proteins, were reported as risk factors in North African countries of Morocco, Egypt, and Tunisia ( 143 – 148 ). Other overexpressed angiogenic proteins reported are EGFR in Tunisia ( 149 ) and IGFBP2 and IGFBP5 in Nigerian women ( 150 ).…”

Section: Resultsmentioning

confidence: 99%

A Review of Cancer Genetics and Genomics Studies in Africa

Rotimi

Salhia

2021

Front. Oncol.

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Cancer is the second leading cause of death globally and is projected to overtake infectious disease as the leading cause of mortality in Africa within the next two decades. Cancer is a group of genomic diseases that presents with intra- and inter-population unique phenotypes, with Black populations having the burden of morbidity and mortality for most types. At large, the prevention and treatment of cancers have been propelled by the understanding of the genetic make-up of the disease of mostly non-African populations. By the same token, there is a wide knowledge gap in understanding the underlying genetic causes of, and genomic alterations associated with, cancer among black Africans. Accordingly, we performed a review of the literature to survey existing studies on cancer genetics/genomics and curated findings pertaining to publications across multiple cancer types conducted on African populations. We used PubMed MeSH terms to retrieve the relevant publications from 1990 to December 2019. The metadata of these publications were extracted using R text mining packages: RISmed and Pubmed.mineR. The data showed that only 0.329% of cancer publications globally were on Africa, and only 0.016% were on cancer genetics/genomics from Africa. Although the most prevalent cancers in Africa are cancers of the breast, cervix, uterus, and prostate, publications representing breast, colorectal, liver, and blood cancers were the most frequent in our review. The most frequently reported cancer genes were BRCA1, BRCA2, and TP53. Next, the genes reported in the reviewed publications’ abstracts were extracted and annotated into three gene ontology classes. Genes in the cellular component class were mostly associated with cell part and organelle part, while those in biological process and molecular function classes were mainly associated with cell process, biological regulation, and binding, and catalytic activity, respectively. Overall, this review highlights the paucity of research on cancer genomics on African populations, identified gaps, and discussed the need for concerted efforts to encourage more research on cancer genomics in Africa.

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Section: Resultsmentioning

confidence: 99%

A Review of Cancer Genetics and Genomics Studies in Africa

Rotimi

Salhia

2021

Front. Oncol.

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“…Such covariates were selected, as these covariates were chosen as the primary control covariates. 14 As calculated by the BMI, core obesity tends to have a greater effect on the prevalence of breast cancer in African-American females than general adiposity. The pre-menopausal women have 21% an elevated value of BMI and 29% of post-menopausal women with an abdomen diameter of 90 cm are also more likely to develop breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Altered MMP-2 activity arising from the involvement of unique MMP-2, this included variants in the degrade of ECM and disturbance of the membrane barrier in the basement. 14 MMP-2 protein has been regulated by immune histochemical approaches in breast carcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

Association between Matrix Metalloproteinas-2 Gene Variants and Pathogenesis of Breast Cancer in Sera of Iraqi Women

Abbas

Al-Tu’ma

Al-Hemerri

2020

J. Contemp. Med. Sci.

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Objective: The current study aims to investigate the role of MMP-2 in breast cancer pathogenesis in Iraqi women. Methods: A forty one women with breast cancer and 45 control women were included in this case-control study. Body mass index, age, smoking; married status, tumor size, degree, subtype, lymph node status, pre and postmenopesua included the phenotypic results. The polymerase chain reaction-PCR-allele specific restriction was used to observe the rs243865 polymorphism. Genomic DNA was extracted from whole blood and genotyping with specific prefixes for amplification of the MMP-2 gene was accomplished as enzyme-restricted PCR products were digested, followed by electrophoresis on 1.5% agarose gel. In order to interpret the researchers' results, numerous statistical analyses were applied. Results: The amplicon size of MMP-2 gene was 304 bp, and following its amplification reactions by allelic specific PCR. The amplification product for MMP-2 gene amplification SNP rs243865 gene polymorphism results exhibited one band of 304 bp, two bands of 304 bp and one band 304 bp for individuals have genotype as wild type (CC), homozygous (TT) and heterozygous (CT), respectively. Genotype frequencies of rs243865 polymorphism were found to be consistent with Hardy–Weinberg equilibrium. Allele frequencies of C allele was 0.57, and the T allele was only 0.43 in cases of breast cancer women patient, while the frequencies of CC, CT, and TT genotypes of the rs243865 SNP were statistically significant as 31.7%, 51.2%, 17.1% respectively. Allele frequencies of C and T were 0.78 and 0.22 for the control group, respectively, the heterozygous genotype (CT) was significantly increased the risk of breast cancer women (OR=0.3, 95% CI;0.12 – 0.8 , P≤ 0.05) with respect to those of the CC wild type. The TT genotype significantly raised the risk of breast cancer women by (OR = 0.2, 95% CI; 0.04 – 0.9, P≤ 0.05). Conclusion: In women with breast cancer, MMP-2 expression is highly association were observed with positive lymph node, histological classification of breast cancer (ll) higher than other classes, and advanced clinical process (ll).

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“…It has been reported that the T allele reduces the expression of MMP-2 (35). Ten studies investigated the association between rs243865 and breast cancer risk, but the results were unclear (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Several authors have hypothesized that this polymorphism may reduce the risk of breast cancer because of less protein expression.…”

Section: Mmp-2 Gene Polymorphisms and Breast Cancer Riskmentioning

confidence: 99%

“…Three studies were identified that investigated the association between rs2285053 in MMP-2 and breast cancer risk. Two studies showed that the rs2285053 T allele rather than the C allele reduced the risk of breast cancer in the Tunisian (OR=0.59; 95% CI=0.46-0.75) (23) and Iranian (OR=0.61; 95% CI=0.37-0.99; p=0.049) (38) populations. However, Beeghly-Fadiel et al (18) did not find any association between CC, CT, TT genotypes of rs2285053 and breast cancer risk in additive models (p=0.436).…”

Section: Mmp-2 Gene Polymorphisms and Breast Cancer Riskmentioning

confidence: 99%

Gene Polymorphisms and Circulating Levels of MMP-2 and MMP-9: A Review of Their Role in Breast Cancer Risk

Dofara

Diorio

2020

Anticancer Res

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MMP-2 and MMP-9 genes have been suggested to play a role in breast cancer. Their functions have been associated with invasion and metastasis of breast cancer; however, their involvement in the development of the disease is not well-established. Herein, we reviewed the literature investigating the association between circulating levels and polymorphisms of MMP-2 and MMP-9 and breast cancer risk. Various studies report conflicting results regarding the relationship of polymorphisms in MMP-2 and MMP-9 and breast cancer risk. Nevertheless, it appears that the T allele in rs243865 and rs2285053 in MMP-2 are associated with reduced risk of breast cancer. In addition, high levels of latent form and low levels of active form of MMP-2 were observed in breast cancer patients compared to controls. For MMP-9, high latent levels and low total levels were found in breast cancer patients compared to controls. Additional studies are needed to comprehend the role of these genes in breast carcinogenesis.Matrix metalloproteinases (MMP) are a family of Zn 2+dependent endopeptidases responsible for cleaving components of the extracellular matrix (1). They are classified into several families according to their structural differences (1, 2). MMP-2 and -9 comprise the gelatinase family that possesses three fibronectin repeats allowing for degradation of denatured collagen (gelatin) and collagens IV and V (2, 3). These gelatinases degrade collagen in the basement membrane (4), as well as other extracellular matrix components, thus promoting extracellular matrix remodeling and consequently play a key role in several physiological processes, such as tissue repair, wound healing, and cell differentiation (5, 6).Gelatinases could be involved in carcinogenesis processes, including cell proliferation, angiogenesis, and tumor metastasis through their proteolytic function (7). Indeed, the literature suggests their involvement in several pathological processes critical for cancer development, including inflammation, angiogenesis, and cell proliferation, as well as in tumor progression (8,9). More specifically, the biological functions of MMP-2 and -9 proteins have been associated with invasive and metastatic stages of breast cancer (10, 11); however, their involvement in breast cancer development is unclear.Herein, we aimed to review and discuss articles which studied the association between gelatinases and breast cancer risk. For this purpose, an electronic search of the MEDLINE (PubMed) database was performed to identify all published studies that evaluated the association of polymorphisms or circulating levels of MMP-2 and MMP-9 with breast cancer risk. Matrix Metalloproteinase-2 (MMP-2)MMP-2 is located on chromosome 16 and codes for gelatinase A. The substrates for this enzyme include gelatin, collagen V, and collagen VI (12). The MMP-2 gene has been studied in several abnormal physiological processes, such as obesity and cancer (13). Polymorphisms that alter the function and efficacy of this protein could be associated with breast cancer ri...

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Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women

Cited by 21 publications

References 36 publications

A Review of Cancer Genetics and Genomics Studies in Africa

A Review of Cancer Genetics and Genomics Studies in Africa

Association between Matrix Metalloproteinas-2 Gene Variants and Pathogenesis of Breast Cancer in Sera of Iraqi Women

Gene Polymorphisms and Circulating Levels of MMP-2 and MMP-9: A Review of Their Role in Breast Cancer Risk

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