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. 2021 Jan;14(1):15.
doi: 10.3892/mco.2020.2177. Epub 2020 Nov 26.

Relationship between MUTYH, OGG1 and BRCA1 mutations and mRNA expression in breast and ovarian cancer predisposition

Carmelo Moscatello  1 , Marta Di Nicola  1 , Serena Veschi  2 , Patrizia Di Gregorio  3 , Ettore Cianchetti  1 , Liborio Stuppia  4 , Pasquale Battista  1 , Alessandro Cama  2 , Maria Cristina Curia  1 , Gitana Maria Aceto  1
Affiliations

Relationship between MUTYH, OGG1 and BRCA1 mutations and mRNA expression in breast and ovarian cancer predisposition

Carmelo Moscatello et al. Mol Clin Oncol. 2021 Jan.

Abstract

The aetiology of breast and ovarian cancer (BC/OC) is multi-factorial. At present, the involvement of base excision repair (BER) glycosylases (MUTYH and OGG1) in BC/OC predisposition is controversial. The present study investigated whether germline mutation status and mRNA expression of two BER genes, MUTHY and OGG1, were correlated with BRCA1 in 59 patients with BC/OC and 50 matched population controls. In addition, to evaluate the relationship between MUTYH, OGG1 and BRCA1, their possible mutual modulation and correlation among mutational spectrum, gene expression and demographic characteristics were evaluated. The results identified 18 MUTYH and OGG1 variants, of which 4 were novel (2 MUTYH and 2 OGG1) in 44 of the 59 patients. In addition, two pathogenic mutations were identified: OGG1 p.Arg46Gln, detected in a patient with BC and a family history of cancer, and MUTYH p.Val234Gly in a patient with OC, also with a family history of cancer. A significant reduced transcript expression in MUTYH was observed (P=0.033) in cases, and in association with the presence of rare variants in the same gene (P=0.030). A significant correlation in the expression of the two BER genes was observed in cases (P=0.004), whereas OGG1 and BRCA1 was significantly correlated in cases (P=0.001) compared with controls (P=0.010). The results of the present study indicated that the relationship among mutational spectrum, gene expression and demographic characteristics may improve the genetic diagnosis and primary prevention of at-risk individuals belonging to families with reduced mRNA expression, regardless of mutation presence.

Keywords: BRCA1; MUTYH; OGG1; base excision repair; breast cancer; gene expression; mutation; ovarian cancer; oxidative stress; prevention.

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References

    1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, F Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941–1953. doi: 10.1002/ijc.31937. - DOI - PubMed
    1. Hiatt RA, Brody JG. Environmental determinants of breast cancer. Annu Rev Public Health. 2018;39:113–133. doi: 10.1146/annurev-publhealth-040617-014101. - DOI - PubMed
    1. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402–2416. doi: 10.1001/jama.2017.7112. - DOI - PubMed
    1. Jezierska-Drutel A, Rosenzweig SA, Neumann CA. Role of oxidative stress and the microenvironment in breast cancer development and progression. Adv Cancer Res. 2013;119:107–125. doi: 10.1016/B978-0-12-407190-2.00003-4. - DOI - PMC - PubMed
    1. Malins DC, Holmes EH, Polissar NL, Gunselman SJ. The etiology of breast cancer. Characteristic alteration in hydroxyl radical-induced DNA base lesions during oncogenesis with potential for evaluating incidence risk. Cancer. 1993;71:3036–3043. doi: 10.1002/1097-0142(19930515)71:10<3036::aid-cncr2820711025>3.0.co;2-p. - DOI - PubMed