Functional promoter variant rs2868371 of HSPB1 is associated with risk of radiation pneumonitis after chemoradiation for non-small cell lung cancer.

Journal Article

PURPOSE: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. RESULTS: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. CONCLUSIONS: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

Full Text

Duke Authors

Cited Authors

  • Pang, Q; Wei, Q; Xu, T; Yuan, X; Lopez Guerra, JL; Levy, LB; Liu, Z; Gomez, DR; Zhuang, Y; Wang, L-E; Mohan, R; Komaki, R; Liao, Z

Published Date

  • April 2013

Published In

Volume / Issue

  • 85 / 5

Start / End Page

  • 1332 - 1339

PubMed ID

  • 23374503

Electronic International Standard Serial Number (EISSN)

  • 1879-355X

International Standard Serial Number (ISSN)

  • 0360-3016

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2012.10.011

Language

  • eng