title: TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy.
abstract: Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152-19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123-17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069-15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings.
authors.affiliation: From the Department of Radiation Oncology (HZ, LS, LL, GL, JZ, YW, MF, WD, ZZ); Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China (MW, YD, QW); Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (QW); Department of Obstetrics and Gynocology, Zhongshan Hospital (TS); and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China (HZ, MW, LS, LL, YD, GL, JZ, YW, MF, WD, ZZ).
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Mengyun
authors.initials: M
authors.lastname: Wang
authors.forename: Tingyan
authors.initials: T
authors.lastname: Shi
authors.forename: Lijun
authors.initials: L
authors.lastname: Shen
authors.forename: Liping
authors.initials: L
authors.lastname: Liang
authors.forename: Yun
authors.initials: Y
authors.lastname: Deng
authors.forename: Guichao
authors.initials: G
authors.lastname: Li
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.forename: Weijuan
authors.initials: W
authors.lastname: Deng
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha