Genetic Variants of NPAT-ATM and AURKA are Associated With an Early Adverse Reaction in the Gastrointestinal Tract of Patients With Cervical Cancer Treated With Pelvic Radiation Therapy

Journal Article · Tue Nov 15 00:00:00 EST 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2010.09.012· OSTI ID:22054451

Ishikawa, Atsuko; Suga, Tomo; Shoji, Yoshimi ^[1]; Kato, Shingo; Ohno, Tatsuya; Ishikawa, Hitoshi ^[2]; Yoshinaga, Shinji ^[3]; Ohara, Kiyoshi ^[4]; Ariga, Hisanori ^[5]; Nomura, Kuninori ^[6]; Shibamoto, Yuta ^[7]; Ishikawa, Ken-Ichi; Moritake, Takashi; Michikawa, Yuichi; Iwakawa, Mayumi ^[1]; Imai, Takashi ^[1]

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1. RadGenomics Project, National Institute of Radiological Sciences, Chiba (Japan)
2. Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)
3. Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan)
4. Tsukuba University Hospital, Tsukuba (Japan)
5. Tohoku University Hospital, Miyagi (Japan)
6. Toyama University Hospital, Toyama (Japan)
7. Nagoya City University Hospital, Aichi (Japan)

Purpose: This study sought to associate polymorphisms in genes related to cell cycle regulation or genome maintenance with radiotherapy (RT)-induced an early adverse reaction (EAR) in patients with cervical cancer. Methods and Materials: This study enrolled 243 cervical cancer patients who were treated with pelvic RT. An early gastrointestinal reaction was graded using the National Cancer Institute Common Toxicity Criteria, version 2. Clinical factors of the enrolled patients were analyzed, and 208 patients were grouped for genetic analysis according to their EAR (Grade {<=}1, n = 150; Grade {>=}2, n = 58). Genomic DNA was genotyped, and association with the risk of EAR for 44 functional single-nucleotide polymorphisms (SNPs) of 19 candidate genes was assessed by single-locus, haplotype, and multilocus analyses. Results: Our analysis revealed two haplotypes to be associated with an increased risk of EAR. The first, comprising rs625120C, rs189037T, rs228589A, and rs183460G, is located between the 5' ends of NPAT and ATM (OR = 1.86; 95% CI, 1.21-2.87), whereas the second is located in the AURKA gene and comprises rs2273535A and rs1047972G (OR = 1.75; 95% CI, 1.10-2.78). A third haplotype, rs2273535T and rs1047972A in AURKA, was associated with a reduced EAR risk (OR = 0.42; 95% CI, 0.20-0.89). The risk of EAR was significantly higher among patients with both risk diplotypes than in those possessing the other diplotypes (OR = 3.24; 95% CI, 1.52-6.92). Conclusions: Individual radiosensitivity of intestine may be determined by haplotypes in the NPAT-ATM and AURKA genes. These variants should be explored in larger association studies in cervical cancer patients.

• OSTI ID: 22054451
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 81, Issue 4; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CELL CYCLE
DNA
GENES
HAZARDS
INTESTINES
NEOPLASMS
PATIENTS
RADIOSENSITIVITY
RADIOTHERAPY
TOXICITY