Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy |
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| Affiliation: | 1. Department of Radiation Oncology, Navy General Hospital, Beijing, China;2. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA;3. Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA;4. Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA;1. Department of Oral Implantology, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, Sichuan, China;2. Department of Advanced Prosthetic Dentistry, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi, Japan;3. Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan;4. Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan;5. Department of Oral Cancer Therapeutics, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi, Japan;1. Medical Physics & Applied Radiation Sciences, McMaster University, Hamilton, ON, Canada;2. Department of Oncology, McMaster University, Hamilton, ON, Canada;3. Department of Radiology, McMaster University, Hamilton, ON, Canada;1. Helmholtz Zentrum Berlin, Hahn-Meitner Platz 1, D-14109 Berlin, Germany;2. Institute Laue-Langevin, 6 rue Jules Horowitz, F-38042 Grenoble, France;3. Paul Scherrer Institut, WHGA 242, CH-5232 Villigen-PSI, Switzerland;1. Department of Surgical Sciences, Uppsala University, Sweden;2. Regional Cancer Centre, Uppsala Örebro Region, Sweden;3. King’s College London, School of Medicine, Division of Cancer Studies, London, UK;4. Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden;5. Department of Surgical and Perioperative Sciences, Umeå University, Sweden;6. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA |
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| Abstract: | BackgroundLIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy.MethodsWe genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders.ResultsMultivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR = 2.97 and 2.23, 95% confidence interval (CI) = 1.32–6.72 and 1.01–4.94, P = 0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR = 2.30 and 2.00, 95% CI = 1.24–4.28 and 1.11–3.62, and P = 0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65 years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0 Gy.ConclusionGenetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings. |
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| Keywords: | Polymorphisms Inflammation Hazards ratio Non-small cell lung cancer Radiation pneumonitis |
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