Correlation between  CCL4  gene polymorphisms and clinical aspects of breast cancer

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Abstract

Breast cancer is a major cause of cancer mortality amongst women. Chemokine (C-C motif) ligand 4 is encoded by the CCL4 gene; specific CCL4 gene polymorphisms are related to the risks and prognoses of various diseases. In this study, we examined whether CCL4 gene single nucleotide polymorphisms (SNPs) predict the risk and progression of breast cancer. Between 2014 and 2016, we recruited 314 patients diagnosed with breast cancer and a cohort of 209 healthy participants (controls) without a history of cancer. Genotyping of the CCL4 rs1634507, rs10491121 and rs1719153 SNPs revealed no significant between-group differences for these polymorphisms. However, amongst luminal A and luminal B subtypes, compared with patients with the AA genotype, those carrying the AG genotype at SNP rs10491121 were less likely to develop lymph node metastasis. In addition, compared with AA carriers, those carrying the AG + GG genotype at SNP rs10491121 were at lower risk of developing distant metastasis, while the presence of the AT genotype at SNP rs1719153 increased the likelihood of pathologic grade (G3 or G4) disease. Variations in the CCL4 gene may help to predict breast cancer progression and metastasis.

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Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.

Ian Ellis, Robert Elston (1991)

Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy.

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A highly significant association between a COMT haplotype and schizophrenia.

Efrat Lev Lehman, Richard Schiffer, Christopher Karp … (2002)

Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of (i) a large sample size-to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; (ii) the use of Ashkenazi Jews, a well defined homogeneous population; and (iii) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype (P=9.5x10-8). The approach presented can be widely implemented for the genetic dissection of other common diseases.

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Highly penetrant hereditary cancer syndromes.

Charis Eng, Kevin Sweet, Rebecca Nagy (2004)

The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Approximately 5-10% of all cancers are inherited, the majority in an autosomal dominant manner with incomplete penetrance. While this is a small fraction of the overall cancer burden worldwide, the molecular genetic discoveries that have resulted from the study of families with heritable cancer have not only changed the way these families are counselled and managed, but have shed light on molecular regulatory pathways important in sporadic tumour development as well. In this review, we consider 10 of the more highly penetrant cancer syndromes, with emphasis on those predisposing to breast, colon, and/or endocrine neoplasia. We discuss the prevalence, penetrance, and tumour spectrum associated with these syndromes, as well as their underlying genetic defects.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Med Sci

Journal ID (iso-abbrev): Int J Med Sci

Journal ID (publisher-id): ijms

Title: International Journal of Medical Sciences

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1449-1907

Publication date Collection: 2018

Publication date (Electronic): 30 July 2018

Volume: 15

Issue: 11

Pages: 1179-1186

Affiliations

[1 ]Department of Surgical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China

[2 ]Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan

[3 ]Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

[4 ]Division of Hematology/Oncology, Department of Medicine, Taipei Medical University-Shuang Ho Hospital, Taiwan

[5 ]Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

[6 ]Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China

[7 ]Department of Medical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China

[8 ]Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China

[9 ]Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan

[10 ]Chinese Medicine Research Center, China Medical University, Taichung, Taiwan

[11 ]Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan

Author notes

✉ Corresponding authors: Chih-Hsin Tang PhD; Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan. E-mail: chtang@ 123456mail.cmu.edu.tw and Chen-Ming Su, PhD; Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. E-mail: ericsucm@ 123456163.com , proof814@ 123456gmail.com

# These authors have contributed equally to this work

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: ijmsv15p1179

DOI: 10.7150/ijms.26771

PMC ID: 6097259

PubMed ID: 30123055

SO-VID: c834bb14-a496-46f3-ad85-4c0c0e03bb0e

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This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Correlation between CCL4 gene polymorphisms and clinical aspects of breast cancer

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Most cited references 20

Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.

A highly significant association between a COMT haplotype and schizophrenia.

Highly penetrant hereditary cancer syndromes.

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