CLINICAL SIGNIFICANCE OF ESTROGEN RECEPTOR GENE ERS1 SNP IN CANCER PATIENTS FROM FAMILIES WITH ONCOLOGICAL PATHOLOGY IN PEDIGREES
Keywords:
cancer of female reproductive system organs, family trees, family cancer syndrome, single nucleotide substitutions, polymorphisms (SNP) of the gene ESR1.Abstract
Aim: to determine genetic risk of oncologic pathology development in family trees of
probands from families with family cancer history and patients with primary-multiple
tumors basing on the results of clinical-genealogical examination and genetic analysis of estrogen receptor gene ESR1 in patients with ovarian cancer and breast cancer. Methods: clinical, morphological, clinical-genealogical and molecular-genetic
studies. Results: it was presented the results of complex of 145 females: 90 patients
with cancer of female reproductive system organs (FRSO), including patients with
primary-multiple tumors with aggregation of tumor pathology in families, and 55 females — control group without cancer family history. It was determined that in families of patients with FRSO cancers the malignant tumors of FRSO, gastro-intestinal
tract and others prevail that corresponds to Lynch II syndrome (family cancer syndrome). Molecular-genetic examination of single nucleotide polymorphism (SNP)
of the gene ESR1 in genomic DNA of peripheral blood and from histological material determined significant increase the frequency of 397СС genotype of the gene
ESR1 in cancer patients and aggregation of malignant pathology in families comparing with frequency of this genotype in female of control group. Statistical processing of these results demonstrated that the risk of malignant pathology development
(odds ratio — OR, 95% confidence interval — СІ) increases in 4.95 times in case of
determination of СС genotype of the gene ESR1 (T-397C), and in case of heterozygous carriage of this gene — in 2.25 times. The presence of TT genotype of the gene
ESR1 (T-397C) reduces the risk of the disease (OR = 0.21). Conclusion: the frequency of АА, AG, GG genotypes of the gene ESR1 (A-351G) also differed in cancer patients comparing with these characteristics in healthy females: significant reduction AA genotype АА to 33.33% versus 67.27% in healthy females (p = 0.001),
significant increase of AG genotype from 32.73 to 57.78% (p = 0.006), tendency of
genotype GG increase — from zero to 8.89% (p = 0.057). This is a basis for clinical-genealogical and molecular genetic study in females with FRSO malignant pathology for detection of polymorphisms (SNP) of estrogen receptor gene (ESR1). The
examined SNPs polymorphisms of ESR1 can be predictors of cancer development
and aggregation of malignant tumors in proband’s family and progeny
References
De Santis D, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA: Cancer J. Clin. 2011, Doi 10.3322/Caac. 20134.
Ebell MH, Culp MB, Radke TJ. A Systematic review of
symptoms for the diagnosis of ovarian cancer. Amer J Prevent Med
; 50 (3): 384–94.
Shchepotin IB, Zotov ОС, Engel ОТ. Female reproductive
system multiple-primary malignant tumors. Oncologia 2009; 11
(4): 249–53 (in Ukrainian).
Peng S, Lü B, Ruan W, et al. Genetic polymorphisms and
breast cancer risk: evidence from meta-analyses, pooled analyses,
and genome-wide association studies. Breast Cancer Res Treat
; 127 (2): 309–24.
Bonadona V, Bonaiti B, Olschwang S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes
in Lynch syndrome. JAMA 2011; 305 (22): 2304–10.
Lee YH, Kim JH, Song GG. Genome-wide pathway analysis
of breast cancer. Tumour Biol 2014; 35 (8): 7699–705.
Filippini SE, Vega A. Breast cancer genes: beyond BRCA1 and
BRCA2. Front Biosci (Landmark Ed) 2013; 18: 1358–72.
Foretova L, Petrakova K, Palacova M, et al. Genetic testing
and prevention of hereditary cancer at the MMCI — over 10 years
of experience. Klin Onkol 2010; 23 (6): 388–400.
Daly MB, Axilbund JE, Buys S, et al. Genetic/familial high-risk
assessment: breast and ovarian. J Natl Compr Canc Netw 2010; 8: 562.
Petrucelli N, Mary BD, Feldman GL. Hereditary breast
and ovarian cancer due to mutations in BRCA1 and BRCA2. Genet Med 2010; 12: 245–59.
Кіtsera N, Helner M, Shparyk Ya, et al. Clinical, genealogical and molecular genetic among twins with familial breast
cancer. Hereditary genetics: Current Res Genetics 2013. S.2.002.
Paliychuk ОV, Rossokha ZІ. The role of mutation 5382insC
in the gene BRCA1 in the development of hereditary and primary-muiltiple tumors. Galytskyi Likarskyi Visnyk (Galicia Medicinal Journal) 2015; 22 (4): 91–3 (in Ukrainian).
Walsh MD, Buchanan DD, Cummings MC, et al. Lynch
syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clin
Cancer Res 2010; 16 (7): 2214–24.
Larsen MJ, Thomassen M, Gerdes AM, Kruse TA. Hereditary breast cancer: clinical, pathological and molecular characteristics. Breast Cancer (Auckl) 2014; 15 (8): 145–55.
Cybulski C, Górski T, Huzarski T, et al. CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 2004; 75 (6): 1131–5.
Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F. Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential. Steroids 2014; 90: 13–29.
Wang S, Sun H, Jia Y, et al. Association of 42 SNPs with
genetic risk for cervical cancer: an extensive meta-analysis. BMC
Med Genet 2015; 15: 16–25.
Wang Y, Chu X, Meng X, Zou F. Association of TGF-β1–
C/T polymorphisms with breast cancer risk: evidence from an
updated meta-analysis. Tumour Biol 2014; 35 (2): 935–42.
Xia L, Gao J, Liu Y, Wu K. Significant association between CYP1A1 T3801C polymorphism and cervical neoplasia
risk: a systematic review and meta-analysis. Tumour Biol 2013;
(1): 223–30.
Paliychuk OV, Polishchuk LZ, Gorovenko NG, et al. Role
of genetic factors in predisposition to formation of multiple-primary tumors of female reproductive system organs. Clin Oncologia 2013; (2): 83–9 (in Ukrainian).
Kitsera NI, Shparyk YaV, Bilynskyi BT, Tril OV. Analysis
of mutations in the genes BRCA1/2 in patients with family/hereditary breast cancer, living in the Lviv region (Ukraine). Oncologia
; 14: 44–9 (in Ukrainian).
Lee YH, Kim JH, Song GG. Genome-wide pathway analysis of breast cancer. Tumour Biol 2014; 35 (8): 7699–705.
Fanale D, Amodeo V, Corsini LR, et al. Breast cancer genome-wide association studies: there is strength in numbers. Oncogene 2012; 31 (17): 2121–8.
Waiserman M, Mekhova LV, Voitenko BP. Epigenetic
«programming» of age-dependent diseases Problemy stareniya I
dolgoletia (Problems of aging and longevity) 2014; 23 (3): 215–
(in Ukrainian).
Dong LM, Potter JD, White E, et al. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA
; 299 (20): 2423–36.
Zhang HY, Liang F, ZL J, et al. PTEN mutation, methylation and expression in breast cancer patients. Oncol Lett 2013;
(1): 161–8.
Depowski PL, Rosenthal SI, Ross JS. Loss of expression of
the PTEN gene protein product is associated with poor outcome
in breast cancer. Mod Pathol 2001; 14 (7): 672–6.
Pohlreich P, Kleibl Z, Kleiblová P, et al. The clinical importance of a genetic analysis of moderate-risk cancer susceptibility genes in breast and other cancer patients from the Czech Repub. Klin Onkol 2012; 25 Suppl: S59–66.
Fernandes GC, Michelli RA, Scapulatempo-Neto C, Palmero EI. Association of polymorphisms with a family history of cancer and the presence of germline mutations in the BRCA1/BRCA2
genes. Hered Cancer Clin Pract 2016; 14: 2. doi: 10.1186/s13053–
–0042–1. eCollection 2016.
Kumar P, Rai V. Methylenetetrahydrofolate reductase gene
C677T polymorphism and breast cancer risk: Evidence for genetic
susceptibility. Meta Gene 2015; 6: 72–84.
Pikor L, Thu K, Vucic E, Lam W. The detection and implication of genome instability in cancer. Cancer Metastasis Rev
; 32 (3–4): 341–52.
