PMID- 36781235 OWN - NLM STAT- MEDLINE DCOM- 20230215 LR - 20230215 IS - 0253-3766 (Print) IS - 0253-3766 (Linking) VI - 45 IP - 2 DP - 2023 Feb 23 TI - [Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy]. PG - 146-152 LID - 10.3760/cma.j.cn112152-20220622-00447 [doi] AB - Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade >/= 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade >/= 2 leukopenia. One hundred and fifty-six (45.0%) had grade >/= 2 diarrhea, two SNPs were significantly associated with the occurrence of grade >/= diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade >/=2 dermatitis, three SNPs that significantly associated with the risk of grade >/=2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade >/=2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer. FAU - Chen, H X AU - Chen HX AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Ren, N X AU - Ren NX AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Yang, J AU - Yang J AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Chen, J N AU - Chen JN AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Lu, Q X AU - Lu QX AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Feng, Y R AU - Feng YR AD - Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Huang, Y AU - Huang Y AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Yin, L L AU - Yin LL AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Lin, D X AU - Lin DX AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Li, Y X AU - Li YX AD - Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Jin, J AU - Jin J AD - Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Tan, W AU - Tan W AD - State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. LA - chi GR - 81972859/National Natural Science Foundation of China/ GR - 2019-I2M-1-003/CAMS Innovation Fund for Medical Sciences/ GR - SKLMO-2021-03/State Key Laboratory of Molecular Oncology Grant/ PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Zhong Liu Za Zhi JT - Zhonghua zhong liu za zhi [Chinese journal of oncology] JID - 7910681 RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Gasdermins) RN - EC 3.4.22.- (Caspases) SB - IM MH - Humans MH - Pyroptosis MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism MH - Gasdermins MH - Chemoradiotherapy/adverse effects MH - *Rectal Neoplasms/genetics/surgery MH - Caspases/genetics/metabolism MH - Diarrhea/chemically induced MH - *Leukopenia/chemically induced/genetics MH - Genetic Variation MH - *Dermatitis OTO - NOTNLM OT - Adverse evens OT - Chemoradiotherapy OT - Polymorphism, single nucleotide OT - Pyroptosis OT - Rectal neoplasms EDAT- 2023/02/14 06:00 MHDA- 2023/02/16 06:00 CRDT- 2023/02/13 20:54 PHST- 2023/02/13 20:54 [entrez] PHST- 2023/02/14 06:00 [pubmed] PHST- 2023/02/16 06:00 [medline] AID - 10.3760/cma.j.cn112152-20220622-00447 [doi] PST - ppublish SO - Zhonghua Zhong Liu Za Zhi. 2023 Feb 23;45(2):146-152. doi: 10.3760/cma.j.cn112152-20220622-00447.