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Molecular and Pharmaco-Epidemiology Unit

Activities

We work on primary and secondary cancer prevention projects, as well as on prognostics and predictive biomarkers of solid tumors (e.g. MC1R polymorphisms and neutrophil-to-lymphocyte ratio, Adiponectin…).

We are interested in investigating the polygenic nature of cancer, by studying the various forms of potential interactions between genetic, phenotypic and environmental factors and their impact on both cancer development and prognosis. The advancement in technologies now allows the production of large numbers of data, generally classified as “-omics”, that need specific approach of statistical analysis. The translation of laboratory results in clinical setting is often complex and needs an integration of different information on a wide spectrum of clinical, molecular, epidemiological and lifestyle factors.

We are studying the interaction between fecal and oral microbiome and biomarkers, such as vitamin D serum level, GC binding protein and VDR polymorphisms, in association with cancer risk and prognosis. Vitamin D acts on immune responses, cell cycle, and metabolic processes and there are increasing evidence on its interaction with the gut microbiota in relationship with different diseases. Our aim is to investigate the correlation between fecal and oral microbiota and vitamin D metabolism in a case-control study and a clinical trial for colorectal cancer patient to assess their role on cancer risk and outcome.

We are also investigating the association between candidate single nucleotide polymorphisms (SNPS) with cancer risk, with particular attention to their direct and indirect effect in cancer risk and to gene-environment interaction. This is of particular importance for assessing preventive strategies that could be applied in a clinical context and be therefore directed to specific at risk categories basing on both genetic and clinical/epidemiological risk factors.

Our group is interested in investigating the role of the minimal active dose of drug than can be used for the management of in situ disease (i.e, low dose tamoxifen for treatment of ER positive in situ neoplasia). We are also interested in studying the possibility to repurpose the large arsenal of approved, non-anticancer drugs for cancer treatment. We focus mainly on the effects of three common drugs such as metformin, beta-blockers and vitamin D.

Our projects are aimed to integrate and assess the importance of epidemiological factors in translational and clinical research. With our researches, we would like to create the basis of personalized prevention and therapeutic programs for cancer that will integrate molecular, genetics and epidemiological risk factors.

  • Publications

    1. De Giorgi V, Grazzini M, Benemei S, Marchionni N, Botteri E, Pennacchioli E, Geppetti P, Gandini S.  Propranolol for Off-label Treatment of Patients With Melanoma: Results From a Cohort Study. JAMA Oncol. 2018 Feb 8;4(2):e172908. CI: 5
    2. Le CP, Nowell CJ, Kim-Fuchs C, Botteri E, Hiller JG, Ismail H, Pimentel MA, Chai MG, Karnezis T, Rotmensz N, Renne G, Gandini S, Pouton CW, Ferrari D, Möller A, Stacker SA, Sloan EK. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun. 2016 Mar 1;7:10634. PMID: 26925549 CI: 48
    3. E. Tagliabue, S. Gandini, J.C. García-Borrón, P. Maisonneuve, J. Newton-Bishop, D. Polsky, D. Lazovich, R. Kumar, P. Ghiorzo, L. Ferrucci, N.A. Gruis, S. Puig, P.A. Kanetsky, T. Motokawa, G. Ribas, M.T. Landi, M.C. Fargnoli, T.H. Wong, A. Stratigos, P. Helsing, G. Guida, P. Autier, J. Han, J. Little, F. Sera, and S. Raimondi for the M-SKIP Study group.  Association of Melanocortin-1 Receptor Variants with Pigmentary Traits in Humans: A Pooled-Analysis from the M-SKIP Project.  Journal of Investigative Dermatology 2016, 136(9): 1914-1917. CI: 4
    4. S. Raimondi, E. Botteri, E. Munzone, C. Cipolla, N. Rotmensz, A. DeCensi, S. Gandini. Use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta-analysis. International Journal of Cancer 2016; 139(1): 212-219. CI: 19
    5. S. Caini, S. Raimondi, V. De Giorgi, H. Johansson, I. Zanna, D. Palli, S. Gandini. Telomere length and the risk of cutaneous melanoma and non-melanoma skin cancer: a review of the literature and meta-analysis.  Journal Of Dermatological Science 2015, 80 (3): 168-174. CI: 11
    6. E. Tagliabue, M.C. Fargnoli, S. Gandini, P. Maisonneuve, F. Liu, M. Kayser, T. Nijsten, J. Han, R. Kumar, N.A. Gruis, L. Ferrucci, W. Branicki, T. Dwyer, L. Blizzard, P. Helsing, P. Autier, J.C. García-Borrón, P.A. Kanetsky, M.T. Landi, J. Little, J. Newton-Bishop, F. Sera, S. Raimondi for the M-SKIP Study Group.  MC1R gene variants and non melanoma skin cancer: a pooled-analysis from the M-SKIP project.  British Journal of Cancer 2015, 113 (2): 354-363. CI: 7
    7. E. Pasquali, J.C. García-Borrón, M.C. Fargnoli, S. Gandini, P. Maisonneuve,V. Bagnardi, C.Specchia, F. Liu, M. Kayser, T. Nijsten, E. Nagore, R. Kumar, J. Hansson, P.A. Kanetsky, P. Ghiorzo, T. Debniak, W. Branicki, N.A. Gruis, J. Han, T. Dwyer, L. Blizzard, M.T. Landi, G. Palmieri, G. Ribas, A. Stratigos, M.L. Council, P. Autier, J. Little, J. Newton-Bishop, F. Sera, S. Raimondi for the M-SKIP Study Group.  MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. International Journal of Cancer 2015, 136 (3): 618-631. CI: 34
    8. Serrano D, Gnagnarella P, Raimondi S, Gandini S. Meta-analysis on vitamin D receptor and cancer risk: focus on the role of TaqI, ApaI, and Cdx2 polymorphisms. Eur J Cancer Prev. 2015 Mar 5. CI: 21
    9. Tagliabue E, Raimondi S, Gandini S.  Meta-analysis of vitamin D-binding protein and cancer risk. Cancer Epidemiol Biomarkers Prev. 2015 Sep 12 CI: 17
    10. Raimondi S, Pasquali E, Gnagnarella P, Serrano D, Disalvatore D, Johansson H, Gandini S. BsmI polymorphism of vitamin D receptor gene and cancer risk: A comprehensive meta-analysis. Mutat Res. 2014 Nov;769:17-34. CI: 14
    11. Caini S, Boniol M, Tosti G, Magi S, Medri M, Stanganelli I, Palli D, Assedi M, Marmol VD, Gandini S. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review andmeta-analysis. Eur J Cancer. 2014 Jul 30. CI: 47
    12. Gnagnarella P, Pasquali E, Serrano D, Raimondi S, Disalvatore D, Gandini S. Vitamin D receptor polymorphism FokI and cancer risk: A comprehensive meta-analysis. Carcinogenesis. 2014 Jul 22. CI: 24
    13. Gandini S, Guerrieri-Gonzaga A, Puntoni M, Decensi  A.Metformin and Breast Cancer Risk. J Clin Oncol. 2013 Mar 1;31(7):973-4.CI: 9
    14. Macis D, Gandini S, Guerrieri-Gonzaga A, Johansson H, Magni P, Ruscica M, Lazzeroni M, Serrano D, Cazzaniga M, Mora S, Feroce I, Pizzamiglio M, Sandri MT,  Gulisano M, Bonanni B, Decensi A. Prognostic effect of circulating adiponectin in a randomized 2 x 2 trial of low-dose tamoxifen and fenretinide in premenopausal women at risk for breast cancer. J Clin Oncol. 2012 Jan 10;30(2):151-7.CI: 43
    15. Autier P, Gandini S, Mullie P. A Systematic Review: Influence of Vitamin Supplementation on Serum 25-Hydroxyvitamin D Concentration. J Clin Endocrinol Metab. 2012 Jun 14. CI: 77
    16. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr. 2012 Jan;95(1):91-100. CI: 344
    17. Pilz S, Iodice S, Zittermann A, Grant WB, Gandini S. Vitamin D Status and Mortality Risk in CKD: A Meta-analysis of Prospective Studies. Am J Kidney Dis. 2011 May 31.CI: 234
    18. De Giorgi V, Grazzini M, Gandini S, Benemei S, Lotti T, Marchionni N, Geppetti P. Treatment With {beta}-Blockers and Reduced Disease Progression in Patients With Thick Melanoma. Arch Intern Med. 2011 Apr 25;171(8):779-81. CI: 119
    19. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, Mullie P, Autier P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2010 May 6. CI: 388
    20. M.C. Fargnoli, S. Gandini, K. Peris, P. Maisonneuve, S. Raimondi.  MC1R variants increase melanoma risk in families with CDKN2A mutations: a meta-analysis.  European Journal of Cancer 2010, 46 (8): 1413-1420. CI: 42
    21. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, Bischoff-Ferrari HA, Cavalie E, Ebeling PR, Fardellone P, Gandini S, Gruson D, Guérin AP, Heickendorff L, Hollis BW, Ish-Shalom S, Jean G, von Landenberg P, Largura A, Olsson T, Pierrot-Deseilligny C, Pilz S, Tincani A, Valcour A, Zittermann A. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev. 2010 Sep;9(11):709-15. CI: 504
    22. Raimondi S, Johansson H, Maisonneuve P, Gandini S. Review and meta-analysis on Vitamin D Receptor polymorphisms and cancer risk. Carcinogenesis. 2009 Jul;30(7):1170-80. CI: 262
    23. Johansson H, Gandini S, Bonanni B, Mariette F, Guerrieri-Gonzaga A, Serrano D, Cassano E, Ramazzotto F, Baglietto L, Sandri MT, Decensi A. Relationships between circulating hormone levels, mammographic percent density and breast cancer risk factors in postmenopausal women. Breast Cancer Res Treat. 2008 Mar;108(1):57-67. CI: 63
    24. S. Raimondi, F. Sera, S. Gandini, S. Iodice, S. Caini, P. Maisonneuve, M.C. Fargnoli. MC1R variants, melanoma and Red Hair Color phenotype: a meta-analysis. International Journal of Cancer 2008, 122 : 2753-2760. CI : 198
    25. Adele Green, Philippe Autier, Mathieu Boniol, Peter Boyle, Jean-Francois Doré, Sara Gandini, Julia Newton-Bishop, Béatrice Secretan, Stephen J Walter, Martin A. Weinstock, Johan Westerdahl. The International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: A systematic review. Int J Cancer. 2007 Jun 1;120(5):1116-22. CI: 114
    26. Decensi A, Gandini S, Serrano D, Cazzaniga M, Pizzamiglio M, Maffini F, Pelosi G, Daldoss C, Omodei U, Johansson H, Macis D, Lazzeroni M, Penotti M, Sironi L, Moroni S, Bianco V, Rondanina G, Gjerde J, Guerrieri-Gonzaga A, Bonanni B. Randomized dose-ranging trial of tamoxifen at low doses in hormone replacement therapy users. J Clin Oncol. 2007 Sep 20;25(27):4201-9. CI: 60
    27. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007 Sep 10;167(16):1730-7. CI: 1382
    28. Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, Melchi CF. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer. 2005 Jan;41(1):45-60.  CI: 958
    29. Gandini S, Sera F, Cattaruzza MS, Pasquini P, Abeni D, Boyle P, Melchi CF. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur J Cancer. 2005 Jan;41(1):28- 44. CI: 620
    30. Gandini S, Sera F, Cattaruzza MS, Pasquini P, Zanetti R, Masini C, Boyle P, Melchi CF.Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer. 2005 Sep;41(14):2040-59.  CI: 595.

PARTNERSHIP

Università degli Studi di Milano

MAIN CREDITS

Ministero della Salute Joint Commission International bollinirosa

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