GENETIC PREDICTORS OF RADIATION-INDUCED MORBIDITY IN PROSTATE CANCER PATIENTS
Keywords:
biomarkers of radiosensitivity; radiation toxicity; radiogenomics
Abstract
Abstract
Cancer survivors often faces adverse effects of treatment, which have a significant impact on morbidity. Normal-tissue side effects following radiotherapy (RT) as one of therapeutic modalities are common and may seriously affect quality of life which is especially important in long-term prostate cancer (PC) survivors. Upgrading in our knowledge in radiation biology have led to the better understanding fact that genetics plays a significant role in determining a patient's predisposition to developing late RT toxicity, leading to the new field of research called “radiogenomics”. With the evolution of DNA sequencing technologies and genomic analysis, radiogenomics has make an appearance as a state-of-the-art science in the field of personalized medicine with the goal of detection the genetic determinants RT adverse reactions.
A single-nucleotide polymorphism (SNPs) - based assay could be used to predict the risk of RT adverse effects along with clinical features and treatment factors. Several SNPs have been identified that are associated with late radiation-induced morbidity in PC patients. Most importantly, these SNPs make up genes expressed in the tissues that are likely at the root of these symptoms, including the bladder, rectum, and intestine, which are most exposed to radiation during PC treatment. Genome-wide association studies are likely to lead to an increasing number of genetic polymorphisms that can predict long-term RT complications.
Finally, radiogenomics attempts to predict which PC patients will show radiosensitivity or radioresistance, so that radiation oncologists as well as surgeons can change treatment accordingly to reduce side effects or increase the RT effectiveness.
References
1. Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020; 70: 7-30
2. Caleb R. Dulaney, Daniel O. Osula, Eddy S. Yang, Soroush Rais-Bahrami, "Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine", Prostate Cancer, vol. 2016, ArticleID 4897515, 10 pages, 2016.
3. Howlader NN, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H. SEER cancer statistics review, 1975–2010. Bethesda, MD: National Cancer Institute. 2013 Apr 21;21:12.
4. Schack LM, Petersen SE, Nielsen S, Lundby L, Høyer M, Bentzen L, Overgaard J, Andreassen CN, Alsner J. Validation of genetic predictors of late radiation-induced morbidity in prostate cancer patients. Acta Oncologica. 2017 Nov 2;56(11):1514-21.
5. Bentzen SM, Constine LS, Deasy JO, et al. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys. 2010;76:S3–S9.
6. Thörnqvist S, Hysing LB, Tuomikoski L, et al. Adaptive radiotherapy strategies for pelvic tumors – a systematic review of clinical implementations. Acta Oncol. 2016;55:943–958.
7. Thor M, Olsson C, Oh JH, et al. Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy. Radiother Oncol. 2015;119:117–122.
8. Thor M, Olsson CE, Oh JH, et al. Relationships between dose to the gastro-intestinal tract and patient-reported symptom domains after radiotherapy for localized prostate cancer. Acta Oncol (Madr). 2015;54:1326–1334.
9. Loganathan A, Schloithe AC, Hutton J, et al. Pudendal nerve injury in men with fecal incontinence after radiotherapy for prostate cancer. Acta Oncol. 2015;54:882–888.
10. Andreassen CN, Rosenstein BS, Kerns SL, et al. Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients. Radiother Oncol. 2016;121:431–439.
11. Palumbo E, Piotto C, Calura E, Fasanaro E, Groff E, Busato F, El Khouzai B, Rigo M, Baggio L, Romualdi C, Zafiropoulos D. Individual radiosensitivity in oncological patients: linking adverse normal tissue reactions and genetic features. Frontiers in oncology. 2019 Oct 1;9:987.
12. Rattay T, Talbot CJ. Finding the genetic determinants of adverse reactions to radiotherapy. Clin Oncol (R Coll Radiol). 2014 May;26(5):301-8. doi: 10.1016/j.clon.2014.02.001. Epub 2014 Apr 1. PMID: 24702740.
13. West CM, Barnett GC. Genetics and genomics of radiotherapy toxicity: towards prediction. Genome medicine. 2011 Aug;3(8):1-5.
14. Borgmann K, Hoeller U, Nowack S, Bernhard M, Röper B, Brackrock S, Petersen C, Szymczak S, Ziegler A, Feyer P, Alberti W. Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy. International Journal of Radiation Oncology* Biology* Physics. 2008 May 1;71(1):256-64.
15. Lobachevsky P, Leong T, Daly P, Smith J, Best N, Tomaszewski J, Thompson ER, Li N, Campbell IG, Martin RF, Martin OA. Compromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity. Cancer letters. 2016 Dec 28;383(2):212-9.
16. De Ruyck K, Van Eijkeren M, Claes K, Morthier R, De Paepe A, Vral A, De Ridder L, Thierens H. Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors: association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lymphocytes. International journal of radiation oncology* biology* physics. 2005 Jul 15;62(4):1140-9.
17. Herskind C, Talbot CJ, Kerns SL, Veldwijk MR, Rosenstein BS, West CML. Radiogenomics: a systems biology approach to understanding genetic risk factors for radiotherapy toxicity? Cancer Lett. (2016) 382:95–109. doi: 10.1016/j.canlet.2016.02.035
18. Pavlopoulou A, Bagos PG, Koutsandrea V, Georgakilas AG. Molecular determinants of radiosensitivity in normal and tumor tissue: a bioinformatic approach. Cancer Lett. (2017) 403:37–47. doi: 10.1016/j.canlet.2017.05.023
19. Herr HW. Quality of life in prostate cancer patients. CA: A Cancer Journal for Clinicians. 1997 Jul;47(4):207-17.
20. SL, Kundu S, Oh JH, et al. The prediction of radiotherapy toxicity using single nucleotide polymorphism-based models: a step toward prevention. Semin Radiat Oncol. 2015;25:281–291
21. Kerns SL, Stock RG, Stone NN, Rath L, Vega A, Fachal L, Gómez-Caamaño A, De Ruysscher D, Lammering G, Parliament M, Blackshaw M. Genome-wide association study identifies a region on chromosome 11q14. 3 associated with late rectal bleeding following radiation therapy for prostate cancer. Radiotherapy and Oncology. 2013 Jun 1;107(3):372-6.
22. Fachal L, Gómez-Caamaño A, Barnett GC, Peleteiro P, Carballo AM, Calvo-Crespo P, Kerns SL, Sánchez-García M, Lobato-Busto R, Dorling L, Elliott RM. A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24. 1. Nature genetics. 2014 Aug;46(8):891-4.
23. Kerns SL, Dorling L, Fachal L, Bentzen S, Pharoah PD, Barnes DR, Gómez-Caamaño A, Carballo AM, Dearnaley DP, Peleteiro P, Gulliford SL. Meta-analysis of genome wide association studies identifies genetic markers of late toxicity following radiotherapy for prostate cancer. EBioMedicine. 2016 Aug 1;10:150-63.
24. West C, Rosenstein BS. Establishment of a radiogenomics consortium. International Journal of Radiation Oncology• Biology• Physics. 2010 Apr 1;76(5):1295-6.
25. Barnett GC, West CM, Dunning AM, Elliott RM, Coles CE, Pharoah PD, Burnet NG. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nature Reviews Cancer. 2009 Feb;9(2):134-42.
26. Cesaretti JA, Stock RG, Atencio DP, Peters SA, Peters CA, Burri RJ, Stone NN, Rosenstein BS. A genetically determined dose–volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy. International Journal of Radiation Oncology* Biology* Physics. 2007 Aug 1;68(5):1410-6.
27. Damaraju S, Murray D, Dufour J, Carandang D, Myrehaug S, Fallone G, Field C, Greiner R, Hanson J, Cass CE, Parliament M. Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer. Clinical Cancer Research. 2006 Apr 15;12(8):2545-54.
28. Hümmerich J, Werle-Schneider G, Popanda O, Celebi O, Chang-Claude J, Kropp S, Mayer C, Debus J, Bartsch H, Schmezer P. Constitutive mRNA expression of DNA repair-related genes as a biomarker for clinical radio-resistance: A pilot study in prostate cancer patients receiving radiotherapy. Int J Radiat Biol. 2006 Aug;82(8):593-604. doi: 10.1080/09553000600883302. PMID: 16966187.
29. Valdagni R, Rancati T, Ghilotti M, Cozzarini C, Vavassori V, Fellin G, Fiorino C, Girelli G, Barra S, Zaffaroni N, Pierotti MA, Gariboldi M. To bleed or not to bleed. A prediction based on individual gene profiling combined with dose-volume histogram shapes in prostate cancer patients undergoing three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1431-40. doi: 10.1016/j.ijrobp.2008.10.021. Epub 2009 Feb 11. PMID: 19211196.
30. De Langhe S, De Ruyck K, Ost P, Fonteyne V, Werbrouck J, De Meerleer G, De Neve W, Thierens H. Acute radiation-induced nocturia in prostate cancer patients is associated with pretreatment symptoms, radical prostatectomy, and genetic markers in the TGFβ1 gene. Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):393-9. doi: 10.1016/j.ijrobp.2012.02.061. Epub 2012 Jun 2. PMID: 22658438.
31. Kerns SL, Ostrer H, Rosenstein BS. Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy. Cancer discovery. 2014 Feb 1;4(2):155-65.
2. Caleb R. Dulaney, Daniel O. Osula, Eddy S. Yang, Soroush Rais-Bahrami, "Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine", Prostate Cancer, vol. 2016, ArticleID 4897515, 10 pages, 2016.
3. Howlader NN, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H. SEER cancer statistics review, 1975–2010. Bethesda, MD: National Cancer Institute. 2013 Apr 21;21:12.
4. Schack LM, Petersen SE, Nielsen S, Lundby L, Høyer M, Bentzen L, Overgaard J, Andreassen CN, Alsner J. Validation of genetic predictors of late radiation-induced morbidity in prostate cancer patients. Acta Oncologica. 2017 Nov 2;56(11):1514-21.
5. Bentzen SM, Constine LS, Deasy JO, et al. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys. 2010;76:S3–S9.
6. Thörnqvist S, Hysing LB, Tuomikoski L, et al. Adaptive radiotherapy strategies for pelvic tumors – a systematic review of clinical implementations. Acta Oncol. 2016;55:943–958.
7. Thor M, Olsson C, Oh JH, et al. Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy. Radiother Oncol. 2015;119:117–122.
8. Thor M, Olsson CE, Oh JH, et al. Relationships between dose to the gastro-intestinal tract and patient-reported symptom domains after radiotherapy for localized prostate cancer. Acta Oncol (Madr). 2015;54:1326–1334.
9. Loganathan A, Schloithe AC, Hutton J, et al. Pudendal nerve injury in men with fecal incontinence after radiotherapy for prostate cancer. Acta Oncol. 2015;54:882–888.
10. Andreassen CN, Rosenstein BS, Kerns SL, et al. Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients. Radiother Oncol. 2016;121:431–439.
11. Palumbo E, Piotto C, Calura E, Fasanaro E, Groff E, Busato F, El Khouzai B, Rigo M, Baggio L, Romualdi C, Zafiropoulos D. Individual radiosensitivity in oncological patients: linking adverse normal tissue reactions and genetic features. Frontiers in oncology. 2019 Oct 1;9:987.
12. Rattay T, Talbot CJ. Finding the genetic determinants of adverse reactions to radiotherapy. Clin Oncol (R Coll Radiol). 2014 May;26(5):301-8. doi: 10.1016/j.clon.2014.02.001. Epub 2014 Apr 1. PMID: 24702740.
13. West CM, Barnett GC. Genetics and genomics of radiotherapy toxicity: towards prediction. Genome medicine. 2011 Aug;3(8):1-5.
14. Borgmann K, Hoeller U, Nowack S, Bernhard M, Röper B, Brackrock S, Petersen C, Szymczak S, Ziegler A, Feyer P, Alberti W. Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy. International Journal of Radiation Oncology* Biology* Physics. 2008 May 1;71(1):256-64.
15. Lobachevsky P, Leong T, Daly P, Smith J, Best N, Tomaszewski J, Thompson ER, Li N, Campbell IG, Martin RF, Martin OA. Compromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity. Cancer letters. 2016 Dec 28;383(2):212-9.
16. De Ruyck K, Van Eijkeren M, Claes K, Morthier R, De Paepe A, Vral A, De Ridder L, Thierens H. Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors: association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lymphocytes. International journal of radiation oncology* biology* physics. 2005 Jul 15;62(4):1140-9.
17. Herskind C, Talbot CJ, Kerns SL, Veldwijk MR, Rosenstein BS, West CML. Radiogenomics: a systems biology approach to understanding genetic risk factors for radiotherapy toxicity? Cancer Lett. (2016) 382:95–109. doi: 10.1016/j.canlet.2016.02.035
18. Pavlopoulou A, Bagos PG, Koutsandrea V, Georgakilas AG. Molecular determinants of radiosensitivity in normal and tumor tissue: a bioinformatic approach. Cancer Lett. (2017) 403:37–47. doi: 10.1016/j.canlet.2017.05.023
19. Herr HW. Quality of life in prostate cancer patients. CA: A Cancer Journal for Clinicians. 1997 Jul;47(4):207-17.
20. SL, Kundu S, Oh JH, et al. The prediction of radiotherapy toxicity using single nucleotide polymorphism-based models: a step toward prevention. Semin Radiat Oncol. 2015;25:281–291
21. Kerns SL, Stock RG, Stone NN, Rath L, Vega A, Fachal L, Gómez-Caamaño A, De Ruysscher D, Lammering G, Parliament M, Blackshaw M. Genome-wide association study identifies a region on chromosome 11q14. 3 associated with late rectal bleeding following radiation therapy for prostate cancer. Radiotherapy and Oncology. 2013 Jun 1;107(3):372-6.
22. Fachal L, Gómez-Caamaño A, Barnett GC, Peleteiro P, Carballo AM, Calvo-Crespo P, Kerns SL, Sánchez-García M, Lobato-Busto R, Dorling L, Elliott RM. A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24. 1. Nature genetics. 2014 Aug;46(8):891-4.
23. Kerns SL, Dorling L, Fachal L, Bentzen S, Pharoah PD, Barnes DR, Gómez-Caamaño A, Carballo AM, Dearnaley DP, Peleteiro P, Gulliford SL. Meta-analysis of genome wide association studies identifies genetic markers of late toxicity following radiotherapy for prostate cancer. EBioMedicine. 2016 Aug 1;10:150-63.
24. West C, Rosenstein BS. Establishment of a radiogenomics consortium. International Journal of Radiation Oncology• Biology• Physics. 2010 Apr 1;76(5):1295-6.
25. Barnett GC, West CM, Dunning AM, Elliott RM, Coles CE, Pharoah PD, Burnet NG. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nature Reviews Cancer. 2009 Feb;9(2):134-42.
26. Cesaretti JA, Stock RG, Atencio DP, Peters SA, Peters CA, Burri RJ, Stone NN, Rosenstein BS. A genetically determined dose–volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy. International Journal of Radiation Oncology* Biology* Physics. 2007 Aug 1;68(5):1410-6.
27. Damaraju S, Murray D, Dufour J, Carandang D, Myrehaug S, Fallone G, Field C, Greiner R, Hanson J, Cass CE, Parliament M. Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer. Clinical Cancer Research. 2006 Apr 15;12(8):2545-54.
28. Hümmerich J, Werle-Schneider G, Popanda O, Celebi O, Chang-Claude J, Kropp S, Mayer C, Debus J, Bartsch H, Schmezer P. Constitutive mRNA expression of DNA repair-related genes as a biomarker for clinical radio-resistance: A pilot study in prostate cancer patients receiving radiotherapy. Int J Radiat Biol. 2006 Aug;82(8):593-604. doi: 10.1080/09553000600883302. PMID: 16966187.
29. Valdagni R, Rancati T, Ghilotti M, Cozzarini C, Vavassori V, Fellin G, Fiorino C, Girelli G, Barra S, Zaffaroni N, Pierotti MA, Gariboldi M. To bleed or not to bleed. A prediction based on individual gene profiling combined with dose-volume histogram shapes in prostate cancer patients undergoing three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1431-40. doi: 10.1016/j.ijrobp.2008.10.021. Epub 2009 Feb 11. PMID: 19211196.
30. De Langhe S, De Ruyck K, Ost P, Fonteyne V, Werbrouck J, De Meerleer G, De Neve W, Thierens H. Acute radiation-induced nocturia in prostate cancer patients is associated with pretreatment symptoms, radical prostatectomy, and genetic markers in the TGFβ1 gene. Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):393-9. doi: 10.1016/j.ijrobp.2012.02.061. Epub 2012 Jun 2. PMID: 22658438.
31. Kerns SL, Ostrer H, Rosenstein BS. Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy. Cancer discovery. 2014 Feb 1;4(2):155-65.
Published
2022/04/07
Section
Mini pregledni članak