CCR5 and p53 codon 72 gene polymorphisms: Implications in breast cancer development

Watanabe, Toru

doi:10.3892/ijmm_00000148

Cited by 19 publications

(6 citation statements)

References 19 publications

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“…The Δ32 allele was found in 7.2% of the control subjects, compared to 2.8% in CRC patients. Our frequencies are close to those of Aoki et al in breast cancer, where Δ32 frequency was 7.77% in controls versus 3.47% in patients [39]. Given the rarity of such a mutational event, many studies did not reveal any association with the clinicopathological features, such as CRC meta-analyses where frequencies of the mutated allele in studied cases displayed no correlation [17,18].…”

Section: Discussionsupporting

confidence: 80%

“…In this context, the impact and the results can be conflicting even in the same type of neoplasms. Some studies indicate that Δ32 polymorphism is associated with cancer risk, such as prostate [45], breast [49,50] and gallbladder cancers [51]; however, other studies have shown that there is no significant association between the mutation and cancer risk in prostate [43,52], breast [39,46,47] and lung cancers [48]. In our study, we report that mutation Δ32 reduced the risks of CRC 0.36-fold (95% CI=0.13-0.82).…”

Section: Discussioncontrasting

confidence: 47%

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The role of CCR5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

Weslati

Ounissi

Hazgui

et al. 2021

ARCH BIOL SCI BELGRA

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Chemokines and their receptors are involved in cancer initiation and progression, including colorectal cancer (CRC) and liver metastasis formation. Our aim was to elucidate C-C chemokine receptor type 5 (CCR5) gene polymorphism (CCR5?32) impact on CRC and colorectal cancer liver metastases (CRLM) occurrence risk. We analyzed the CCR5 gene mutational status in 108 primary CRC cases, 35 CRLM and 248 healthy individuals, and evaluated CCR5 expression in healthy tissue and tumors. Rare allele ??32? was more frequent in controls (7.2% vs 2.8% in CRC). All 35 metastases had wild-type CCR5. Our analysis showed that CCR5 wild type has a significant risk of 2.73-fold (95% CI=1.22-7.31) to cause CRC while ?32 reduced the risks 0.36-fold (95% CI=0.13-0.82). For CRC, CCR5 correlated with left-sided tumors and liver metastases (P=0.040 and P= 0.039 respectively). As for CRLM, no correlation was found. Immunohistochemical profile analysis of CCR5 revealed a significant association with the male gender (P=0.049) and non-mucinous carcinomas (P< 0.001) in primary CRC. CCR5 expression revealed an association with the degree of tumor differentiation for both CRC and CRLM (P < 0.001). CCR5?32 might be a protective factor against CRC development and dissemination.

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Section: Discussionsupporting

confidence: 80%

Section: Discussioncontrasting

confidence: 47%

The role of CCR5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

Weslati

Ounissi

Hazgui

et al. 2021

ARCH BIOL SCI BELGRA

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“…CCR5 and its ligands, particularly CCL5 have been thought to support tumor growth either directly, by driving the migration of tumor cells to tumor sites, and mostly by recruiting MDSC and dendritic cells to the tumor site [ 96 , 97 , 98 , 99 , 100 ]. Many studies showed a clear link between CCR5 and CCR5 ligands polymorphism or differential gene signature and several cancer diseases, among them: prostate cancer, breast cancer, glioblastoma, myeloid leukemia, pancreatic adenocarcinoma, Non-Small Cell Lung Cancer (NSCLC), metastatic melanoma, metastatic colorectal cancer and others [ 98 , 99 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. Following Balistreri et al [ 129 ] that observed a very low prevalence of prostate cancer in men with CCR5 delta 32 mutations, which also confers HIV resistance, we have used mice lacking CCR5 to uncover the contribution of CCR5 to the cancer resistance and found that in these mice accumulation of MDSC at the tumor site is inadequate [ 130 ].…”

Section: Key Chemokine-chemokine Receptor Interactions That Support Tumor Growthmentioning

confidence: 99%

Chemokines in the Landscape of Cancer Immunotherapy: How They and Their Receptors Can Be Used to Turn Cold Tumors into Hot Ones?

Karin

2021

Cancers

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Over the last decade, monoclonal antibodies to immune checkpoint inhibitors (ICI), also known as immune checkpoint blockers (ICB), have been the most successful approach for cancer therapy. Starting with mAb to cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors in metastatic melanoma and continuing with blockers of the interactions between program cell death 1 (PD-1) and its ligand program cell death ligand 1 (PDL-1) or program cell death ligand 2 (PDL-2), that have been approved for about 20 different indications. Yet for many cancers, ICI shows limited success. Several lines of evidence imply that the limited success in cancer immunotherapy is associated with attempts to treat patients with “cold tumors” that either lack effector T cells, or in which these cells are markedly suppressed by regulatory T cells (Tregs). Chemokines are a well-defined group of proteins that were so named due to their chemotactic properties. The current review focuses on key chemokines that not only attract leukocytes but also shape their biological properties. CXCR3 is a chemokine receptor with 3 ligands. We suggest using Ig-based fusion proteins of two of them: CXL9 and CXCL10, to enhance anti-tumor immunity and perhaps transform cold tumors into hot tumors. Potential differences between CXCL9 and CXCL10 regarding ICI are discussed. We also discuss the possibility of targeting the function or deleting a key subset of Tregs that are CCR8+ by monoclonal antibodies to CCR8. These cells are preferentially abundant in several tumors and are likely to be the key drivers in suppressing anti-cancer immune reactivity.

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“…The migration of regulatory immune cells to tumor sites can create an immunosuppressor environment proper for cancer development. Also, cancer cells can subvert the anti-tumor action of chemokine-ligand interactions (187)(188)(189)(190)(191). Of note, CD4+ T cells are important modulators of the immune response, acting as drivers for the action of effector cells.…”

Section: Ccr5d32 In Cancermentioning

confidence: 99%

“…Aoki et al (188) assessed the CCR5D32 frequency in individuals with breast cancer and healthy women. However, no significant difference was observed between groups.…”

Section: Ccr5d32 In Cancermentioning

confidence: 99%

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

Kulmann-Leal

Ellwanger

2021

Front. Immunol.

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The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in the CCR5 gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.

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CCR5 and p53 codon 72 gene polymorphisms: Implications in breast cancer development

Cited by 19 publications

References 19 publications

The role of CCR5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

The role of CCR5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

Chemokines in the Landscape of Cancer Immunotherapy: How They and Their Receptors Can Be Used to Turn Cold Tumors into Hot Ones?

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

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