SNPs in the promoter region may affect the expression of a gene either by creating or removing regulatory elements such as transcription factors binding sites, enhancer and response elements. Several of the variants in the 5flanking regions in our present studies such as the Sp1 site of CYP17 or a pentanucleotide repeat of GSTP1 are currently investigated functionally. Assays such as EMSA, CHIP and luciferase reporter systems are used. In addition to genetic regulatory element epigenetic changes may also be influenced by SNPs. Extensive methylation of the promoter area of GSTP1 and exon 1 are observed in vivinity to the studied pentanucleotide repeat. GSTP1 plays a key role in regulating the Map kinase pathway via protein-protein interactions. GSTP1 is an inhibitor of c-Jun N-terminal kinase 1 (JNK1), a kinase involved in stress response, apoptosis and cellular proliferation (X).
Kramer I, Hooning MJ, Mavaddat N, Hauptmann M, Keeman R, Steyerberg EW, Giardiello D, Antoniou AC, Pharoah PDP, Canisius S, Abu-Ful Z, Andrulis IL, Anton-Culver H, Aronson KJ, Augustinsson A, Becher H, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Bogdanova NV, Bojesen SE, Bolla MK, Bonanni B, Brauch Het al.(2020) Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk Am J Hum Genet(in press) DOI 10.1016/j.ajhg.2020.09.001, PubMed 33022221
Tahiri A, Tekpli X, Satheesh SV, DeWijn R, Lüders T, Bukholm IR, Hurtado A, Geisler J, Kristensen VN(2020) Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer Breast Cancer Res Treat, 183(3), 585-598 DOI 10.1007/s10549-020-05763-7, PubMed 32710281
Bergholtz H, Kumar S, Wärnberg F, Lüders T, Kristensen V, Sørlie T(2020) Comparable cancer-relevant mutation profiles in synchronous ductal carcinoma in situ and invasive breast cancer Cancer Rep (Hoboken), 3(3), e1248 DOI 10.1002/cnr2.1248, PubMed 32671987