Association of cyclin‐dependent kinase inhibitor 2A/B with increased risk of developing breast cancer

Abstract

There is a growing body of data reporting the association of genetic alterations in chromosome 9P21 with the risk of developing cancer. In the current study, we studied the association of a genetic variant in CDKN2A/B, rs1333049, with the risk of developing breast cancer. A total of 339 participants with and without breast cancer entered to the study. Genotyping was done by the TaqMan real‐time polymerase chain reaction (RT‐PCR) method and gene expression analysis was ran by RT‐PCR. Our data showed that the minor allele homozygote in the total population was 10%, whereas for heterozygote was 38%. The dominant genetic model demonstrated that individuals with breast cancer had advanced TNM classification. Moreover, the logistic regression revealed that individuals who had CC/CG genotypes might have an enhanced risk of developing breast cancer when compared to the holders of GG genotype (e.g., OR = 2.8; 95% CI,1.4–5.4; p = .001), after regulated for confounders; age and body mass index. Furthermore, our analysis showed that the CDKN2A/B gene was downregulated in patients (p < .001). We showed a meaningful relationship of CDKN2A/B with the risk of breast cancer, cancer, showing the importance of studies in great sample size and several centers for studying the value of the marker as a risk classification in the management of patients with breast cancer.

The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer

“…Individuals with a TT genotype had a greater susceptibility for colorectal cancer. In line with our results, recent studies have also indicated the prognostic role of CDKN2A/B in pancreatic, lung, breast, melanoma and ovarian cancers (Qiu et al, 2015[ 19 ]; Seifi et al, 2019[ 24 ]; Campa et al, 2016[ 4 ]; Schuster et al, 2014[ 23 ]). This observation may be explained by the role of CDKN2A/B in suppressing cellular proliferation and inducing tumor cell death.…”

“…Recently, multiple molecular mechanisms have been reported in CRC tumorigenesis including inactivation of tumor suppressor genes (Rahmani et al, 2018[ 20 ]; Soleimani et al, 2018[ 28 ], 2020[ 29 ]; Bahreyni et al, 2018[ 2 ]; Binabaj et al, 2018[ 3 ]). Several genetic association studies have suggested that genetic variations on chromosome 9p21 may be involved in various malignancies including leukemia, glioma, ovarian, breast and pancreatic cancers (Congrains et al,2013[ 5 ]; Dębniak et al, 2005[ 6 ]; Sherborne et al, 2010[ 27 ]; Qiu et al, 2015[ 19 ]; Gu et al, 2013[ 9 ]; Seifi et al, 2019[ 24 ]; Abdeahad et al, 2020[ 1 ]). This region encodes for cyclin‐dependent kinase inhibitors A and B known as CDKN2A/B which contributes in various metabolic and pathological disorders such as diabetes, metabolic syndrome, cardiovascular and Alzheimer diseases (Hannou et al, 2015[ 10 ]; Mehramiz et al, 2018[ 16 ]; Yu et al, 2010[ 34 ]; Zeggini et al, 2007[ 35 ]).…”

Identification of novel autoantibody signatures and evaluation of a panel of autoantibodies in breast cancer

“… 31 , 32 CDKN2A/p16 has a meaningful association with the risk of BC and it is expected to be a candidate gene for BC. 33 BRCA2 gene is a confirmed BC susceptibility gene, 34 which could lead to the development of BC. 35 HRAS is related to BC and could be a valuable screening biomarker for women.…”

A systematic review: breast cancer susceptibility genes

“…Correcting the DNA mismatch progress [19] Cell cycle regulation genes TP53 Forming a homotetramer binding to TP53 response elements in DNA [21] PTEN Inhibiting of the DNA proliferation at the G1-S transition [24] DNAH11 Activating of p38 mitogen-activated protein kinase (MAPK) pathway [28] CDKN2A/B Inhibiting of the DNA proliferation at the G1-S transition [30] MICA Modulation in immune response regulation for cell cycles [31] Cell-to-cell adhesion genes CDH1 Coding E-cadherin adhesion protein [32] Metabolism genes PON1 Coding a multifactorial antioxidant enzyme [35] ABC Encoding large membrane proteins relating the energy dependent transport of xenobiotics [38] 3 Breast cancer susceptibility genes [10] . Two cohort studies by Engel and Fischer [11] indicated that the cumulative risk of first-time breast cancer at age 60 was 61.8% for BRCA1 mutation carriers, 43.2% for BRCA2 mutation carriers and 15.7% for non-carriers.…”

“…As a tumor suppressor, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) genes inhibit the cell cycle at the G1-S border. By logistic regression, S. Seifi and F. Pouya found that individuals with CC/CG genotypes might have higher risk of breast cancer (OR =2.8, P=0.001) compared with the normal genotypes [30].…”