@misc{oai:repo.qst.go.jp:00070983,
 author = {Imai, Takashi and Suga, Tomo and Otsuka, Yoshimi and Nakawatari, Miyako and Ishikawa, Atsuko and 今井 高志 and 菅 智 and 荘司 好美 and 中渡 美也子 and 石川 敦子},
 month = {Nov},
 note = {Purpose: Hyaluronan (HA), a polysaccharide, is synthesized by a hyaluronan synthase (HAS). HA interacts with cells in dynamic processes such as embryogenesis and oncogenesis through interactions with several types of surface receptors like CD44 that play a role in regulating important signaling pathways, including the PI3K pathway. To identify predictive markers for radiotherapy effectiveness in cervical cancer, we have been analyzing the expression and genetic variation of some key genes such as FGF2, CD44, and HAS1. This study sought to determine the association between polymorphisms in CD44 and HAS1 genes with radiotherapy effectiveness in patients with cervical cancer.
Materials and Methods: The study population comprised 121 cervical cancer patients who were treated with pelvic radiotherapy (the median dose of external beam = 50.6 Gy [range, 45.0 - 60.6 Gy] and median dose of brachytherapy = 24.0 Gy [range, 19.0 - 36.5 Gy]). The patients were defined as good (n = 82, mean age = 61 years [range, 32-83 years]) or poor (n = 39, mean age = 54 years [36-82 years]) responders on the basis of their 2-year disease-free survival. Genomic DNA was obtained from their blood samples and was genotyped using 19 SNPs in CD44 and 4 SNPs in HAS1. The association between each SNP and prognosis was evaluated by multivariate logistic regression analysis conditioned on the data pertaining to smoking, histological classification (squamous cell carcinoma/adenocarcinoma), and the International Federation of Gynecology and Obstetrics (FIGO) staging (I, II, III, IVA) of the tumors.
Results: In logistic regression analysis conditioned on FIGO staging and smoking habits (the other factors did not contribute to the final model), P-values of 0.0056 was obtained for the SNP, T-2016C in CD44 (OR = 2.49, 95% CI = 1.31 - 4.76). The variant was located in the 5' upstream region of the gene, suggesting that patients with the variant contribute to produce different amounts of CD44. 
Conclusions: Thus, radiotherapy effectiveness in patients with cervical cancer may be predicted, at least in part, by the genotype of CD44. Because of the limited sample size used in this study, further replication studies and functional analyses are required to confirm the results of the association analysis. However, the present data may be useful for analyzing the mechanisms underlying interaction between HA and CD44 and the subsequent cervical cancer-associated signaling., CSH Asia / ICMS (The International Cancer Microenvironment Society) Joint Conference on Tumor Microenvironment},
 title = {Association of polymorphisms in hyaluronan receptor CD44 with radiotherapy effectiveness in patients with cervical cancer},
 year = {2012}
}