循環器ジャーナル68巻1号

2020年01月発行

特集 U40世代が描く心不全診療の現状と未来—基礎研究を識り，臨床を素心深考する Ⅰ．心筋症

—基礎編—がん治療関連性心血管障害の予後予測因子はありますか？

著者： 野村征太郎¹

所属機関： ¹東京大学医学部附属病院循環器内科

ページ範囲：P.62 - P.66

Point
・GWAS解析により，がん治療関連心筋症の機序にかかわる分子が同定された．
・タイチン遺伝子の短縮型変異は，がん治療関連心筋症の予測因子になりうる．
・遺伝要因・臨床的背景・治療要因を統合したリスク層別化の構築が求められる．

参考文献

1) Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al:2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines:The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology（ESC）. Eur Heart J 37:2768-2801, 2016

2) Nicol M, Baudet M, Cohen-Solal A:Subclinical Left Ventricular Dysfunction During Chemotherapy. Card Fail Rev 5:31-36, 2019

3) Linschoten M, Teske AJ, Cramer MJ, et al:Chemotherapy-Related Cardiac Dysfunction:A Systematic Review of Genetic Variants Modulating Individual Risk. Circ Genom Precis Med 11:e001753, 2018

4) Cardinale D, Colombo A, Bacchiani G, et al:Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 131:1981-1988, 2015

5) Felker GM, Thompson RE, Hare JM, et al:Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 342:1077-1084, 2000

6) Krajinovic M, Elbared J, Drouin S, et al:Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia. Pharmacogenomics J 16:530-535, 2016

7) Lubieniecka JM, Graham J, Heffner D, et al:A discovery study of daunorubicin induced cardiotoxicity in a sample of acute myeloid leukemia patients prioritizes P450 oxidoreductase polymorphisms as a potential risk factor. Front Genet 4:231, 2013

8) Wojnowski L, Kulle B, Schirmer M, et al:NAD（P）H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 112:3754-3762, 2005

9) Cascales A, Pastor-Quirante F, Sánchez-Vega B, et al:Association of anthracycline-related cardiac histological lesions with NADPH oxidase functional polymorphisms. Oncologist 18:446-453, 2013

10) Cascales A, Sánchez-Vega B, Navarro N, et al:Clinical and genetic determinants of anthracycline-induced cardiac iron accumulation. Int J Cardiol 154:282-286, 2012

11) Lipshultz SE, Lipsitz SR, Kutok JL, et al:Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer 119:3555-3562, 2013

12) Wang X, Liu W, Sun CL, et al:Hyaluronan synthase 3 variant and anthracycline-related cardiomyopathy:a report from the children's oncology group. J Clin Oncol 32:647-653, 2014

13) Blanco JG, Sun CL, Landier W, et al:Anthracycline-related cardiomyopathy after childhood cancer:role of polymorphisms in carbonyl reductase genes--a report from the Children's Oncology Group. J Clin Oncol 30:1415-1421, 2012

14) Visscher H, Ross CJ, Rassekh SR, et al:Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr Blood Cancer 60:1375-1381, 2013

15) Visscher H, Ross CJ, Rassekh SR, et al:Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J Clin Oncol 30:1422-1428, 2012

16) Semsei AF, Erdelyi DJ, Ungvari I, et al:ABCC1 polymorphisms in anthracycline-induced cardiotoxicity in childhood acute lymphoblastic leukaemia. Cell Biol Int 36:79-86, 2012

17) Zhang S, Liu X, Bawa-Khalfe T, et al:Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 18:1639-1642, 2012

18) Aminkeng F, Bhavsar AP, Visscher H, et al:A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer. Nat Genet 47:1079-1084, 2015

19) Windsor RE, Strauss SJ, Kallis C, et al:Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma:a pilot study. Cancer 118:1856-1867, 2012

20) Wang X, Sun CL, Quiñones-Lombraña A, et al:CELF4 Variant and Anthracycline-Related Cardiomyopathy:A Children's Oncology Group Genome-Wide Association Study. J Clin Oncol 34:863-870, 2016

21) Cooper TA, Ordahl CP:A single cardiac troponin T gene generates embryonic and adult isoforms via developmentally regulated alternate splicing. J Biol Chem 260:11140-11148, 1985

22) Crone SA, Zhao YY, Fan L, et al:ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 8:459-465, 2002

23) Beauclair S, Formento P, Fischel JL, et al:Role of the HER2［Ile655Val］genetic polymorphism in tumorogenesis and in the risk of trastuzumab-related cardiotoxicity. Ann Oncol 18:1335-1341, 2007

24) Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, et al:Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy. Circulation 140:31-41, 2019

25) Khera AV, Chaffin M, Aragam KG, et al:Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 50:1219-1224, 2018

26) Duncan L, Shen H, Gelaye B, et al:Analysis of polygenic risk score usage and performance in diverse human populations. Nat Commun 10:3328, 2019