Role of Polymorphisms of FAM13A, PHLDB1, and CYP24A1 in Breast Cancer Risk

Author(s): Ying Wei, Xiaolin Wang, Zhe Zhang, Mingrui Xie, Yuyao Li, Hongxin Cao, Xinhan Zhao*.

Journal Name: Current Molecular Medicine

Volume 19 , Issue 8 , 2019

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Abstract:

Background: Single-nucleotide polymorphisms (SNPs) are important indicators of susceptibility to breast cancer.

Objective: To assess the associations between SNPs in the FAM13A, PHLDB1, and CYP24A1 gene and breast cancer risk in the Chinese Han population.

Methods: We performed a case-control study including 379 female breast cancer patients and 407 female healthy controls. The three SNPs were genotyped using Agena MassARRAY platform. The χ2 test was used to compare alleles and genotypes frequencies of polymorphisms between case and control groups. Genetic models analyses to assess the associations between SNPs and breast cancer risk by computing odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RegulomeDB and HaploReg databases were used to calculate possible functional effects of polymorphisms.

Results: Overall analysis results showed that rs4809957 was associated with an increased risk of breast cancer (allele A: OR = 1.27, 95% CI: 1.03-1.55, p = 0.024; AA vs. GG: OR = 1.80, 95% CI: 1.15–2.82, p = 0.010; recessive model: OR = 1.70, 95% CI: 1.12–2.58, p = 0.012); and rs1059122 was found to be associated with a reduced breast cancer risk in the recessive model (OR = 0.71, 95% CI: 0.51–0.98, p = 0.039). Stratification analysis found significant associations between the three SNPs (rs1059122, rs17748, and rs4809957) and breast cancer risk.

Conclusion: Our results suggested that rs1059122 (FAM13A), rs17748 (PHLDB1), and rs4809957 (CYP24A1) might contribute to breast cancer susceptibility in the Chinese Han population. Future studies with large samples are required to confirm our findings, as well as functional studies are needed to explore their function in the breast cancer development.

Keywords: Breast Neoplasms, FAM13A, PHLDB1, CYP24A1, single nucleotide polymorphisms, cancer.

[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-32.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[3]
Rojas K, Stuckey A. Breast cancer epidemiology and risk factors. Clin Obstet Gynecol 2016; 59(4): 651-72.
[http://dx.doi.org/10.1097/GRF.0000000000000239] [PMID: 27681694]
[4]
Winters S, Martin C, Murphy D, Shokar NK. Breast cancer epidemiology, prevention, and screening. Prog Mol Biol Transl Sci 2017; 151: 1-32.
[http://dx.doi.org/10.1016/bs.pmbts.2017.07.002] [PMID: 29096890]
[5]
Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol 2010; 4(3): 174-91.
[http://dx.doi.org/10.1016/j.molonc.2010.04.011] [PMID: 20542480]
[6]
Listed N. Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer 2000; 83(10): 1301-8.
[http://dx.doi.org/10.1054/bjoc.2000.1407] [PMID: 11044354]
[7]
Zhou L, He N, Feng T, Geng T, Jin T, Chen C. Association of five single nucleotide polymorphisms at 6q25.1 with breast cancer risk in northwestern China. Am J Cancer Res 2015; 5(8): 2467-75.
[PMID: 26396922]
[8]
Xia P, Li B, Geng T, et al. FGFR2 gene polymorphisms are associated with breast cancer risk in the Han Chinese population. Am J Cancer Res 2015; 5(5): 1854-61.
[PMID: 26175953]
[9]
Ren HT, Li YM, Wang XJ, et al. PD-1 rs2227982 polymorphism is associated with the decreased risk of breast cancer in northwest chinese women: A hospital-based observational study. Medicine (Baltimore) 2016; 95(21)e3760
[http://dx.doi.org/10.1097/MD.0000000000003760] [PMID: 27227944]
[10]
Dai ZJ, Liu XH, Ma YF, et al. Association between single nucleotide polymorphisms in DNA polymerase kappa gene and breast cancer risk in chinese han population: A STROBE-compliant observational study. Medicine (Baltimore) 2016; 95(2)e2466
[http://dx.doi.org/10.1097/MD.0000000000002466] [PMID: 26765445]
[11]
Cohen M, Reichenstein M, Everts-van der Wind A, et al. Cloning and characterization of FAM13A1-a gene near a milk protein QTL on BTA6: evidence for population-wide linkage disequilibrium in Israeli Holsteins. Genomics 2004; 84(2): 374-83.
[http://dx.doi.org/10.1016/j.ygeno.2004.03.005] [PMID: 15234000]
[12]
Ridley AJ. Rho family proteins: Coordinating cell responses. Trends Cell Biol 2001; 11(12): 471-7.
[http://dx.doi.org/10.1016/S0962-8924(01)02153-5] [PMID: 11719051]
[13]
Katoh M, Katoh M. Identification and characterization of human LL5A gene and mouse Ll5a gene in silico. Int J Oncol 2003; 23(5): 1477-83.
[http://dx.doi.org/10.3892/ijo.23.5.1477] [PMID: 14532993]
[14]
Lopes N, Sousa B, Martins D, et al. Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions. BMC Cancer 2010; 10: 483.
[http://dx.doi.org/10.1186/1471-2407-10-483] [PMID: 20831823]
[15]
Young RP, Hopkins RJ, Hay BA, Whittington CF, Epton MJ, Gamble GD. FAM13A locus in COPD is independently associated with lung cancer - evidence of a molecular genetic link between COPD and lung cancer. Appl Clin Genet 2010; 4: 1-10.
[http://dx.doi.org/10.2147/TACG.S15758] [PMID: 23776362]
[16]
Shete S, Hosking FJ, Robertson LB, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 2009; 41(8): 899-904.
[http://dx.doi.org/10.1038/ng.407] [PMID: 19578367]
[17]
Dong J, Hu Z, Wu C, et al. Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population. Nat Genet 2012; 44(8): 895-9.
[http://dx.doi.org/10.1038/ng.2351] [PMID: 22797725]
[18]
Chen H, Sun B, Zhao Y, et al. Fine mapping of a region of chromosome 11q23.3 reveals independent locus associated with risk of glioma. PLoS One 2012; 7(12)e52864
[http://dx.doi.org/10.1371/journal.pone.0052864] [PMID: 23300798]
[19]
Li S, Jin T, Zhang J, et al. Polymorphisms of TREH, IL4R and CCDC26 genes associated with risk of glioma. Cancer Epidemiol 2012; 36(3): 283-7.
[http://dx.doi.org/10.1016/j.canep.2011.12.011] [PMID: 22369735]
[20]
Chen W, Zheng R, Zhang S, et al. Cancer incidence and mortality in China, 2013. Cancer Lett 2017; 401: 63-71.
[http://dx.doi.org/10.1016/j.canlet.2017.04.024] [PMID: 28476483]
[21]
Yang B, Heng L, Du S, et al. Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study. Med Sci Monit 2015; 21: 1983-8.
[http://dx.doi.org/10.12659/MSM.893723] [PMID: 26156397]
[22]
Jin Z, Chung JW, Mei W, et al. Regulation of nuclear-cytoplasmic shuttling and function of Family with sequence similarity 13, member A (Fam13a), by B56-containing PP2As and Akt. Mol Biol Cell 2015; 26(6): 1160-73.
[http://dx.doi.org/10.1091/mbc.E14-08-1276] [PMID: 25609086]
[23]
Jiang Z, Lao T, Qiu W, et al. A Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of β-Catenin. Am J Respir Crit Care Med 2016; 194(2): 185-97.
[http://dx.doi.org/10.1164/rccm.201505-0999OC] [PMID: 26862784]
[24]
Goto-Yamaguchi L, Yamamoto-Ibusuki M, Yamamoto Y, et al. Therapeutic predictors of neoadjuvant endocrine therapy response in estrogen receptor-positive breast cancer with reference to optimal gene expression profiling. Breast Cancer Res Treat 2018; 172(2): 353-62.
[http://dx.doi.org/10.1007/s10549-018-4933-5] [PMID: 30151737]
[25]
Zhou QL, Jiang ZY, Mabardy AS, et al. A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes. J Biol Chem 2010; 285(36): 27581-9.
[http://dx.doi.org/10.1074/jbc.M110.146886] [PMID: 20587420]
[26]
Hotta A, Kawakatsu T, Nakatani T, et al. Laminin-based cell adhesion anchors microtubule plus ends to the epithelial cell basal cortex through LL5α/β. J Cell Biol 2010; 189(5): 901-17.
[http://dx.doi.org/10.1083/jcb.200910095] [PMID: 20513769]
[27]
Welsh J. Vitamin D and prevention of breast cancer. Acta Pharmacol Sin 2007; 28(9): 1373-82.
[http://dx.doi.org/10.1111/j.1745-7254.2007.00700.x] [PMID: 17723171]
[28]
Fuhrman BJ, Freedman DM, Bhatti P, et al. Sunlight, polymorphisms of vitamin D-related genes and risk of breast cancer. Anticancer Res 2013; 33(2): 543-51.
[PMID: 23393347]
[29]
Albertson DG, Ylstra B, Segraves R, et al. Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet 2000; 25(2): 144-6.
[http://dx.doi.org/10.1038/75985] [PMID: 10835626]
[30]
Chen XQ, Mao JY, Li WB, et al. Association between CYP24A1 polymorphisms and the risk of colonic polyps and colon cancer in a Chinese population. World J Gastroenterol 2017; 23(28): 5179-86.
[http://dx.doi.org/10.3748/wjg.v23.i28.5179] [PMID: 28811712]
[31]
Gong C, Long Z, Yu Y, et al. Dietary factors and polymorphisms in vitamin D metabolism genes: the risk and prognosis of colorectal cancer in northeast China. Sci Rep 2017; 7(1): 8827.
[http://dx.doi.org/10.1038/s41598-017-09356-1] [PMID: 28821819]


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Article Details

VOLUME: 19
ISSUE: 8
Year: 2019
Page: [579 - 588]
Pages: 10
DOI: 10.2174/1566524019666190619125109
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