Association of a missense single nucleotide polymorphism, Cys1367Arg of the WRN gene, with the risk of bone and soft tissue sarcomas in Japan

Robert Nakayama, Yasunori Sato, Mitsuko Masutani, Hideki Ogino, Fumihiko Nakatani, Hirokazu Chuman, Yasuo Beppu, Hideo Morioka, Hiroo Yabe, Hiroshi Hirose, Haruhiko Sugimura, Hiromi Sakamoto, Tsutomu Ohta, Yoshiaki Toyama, Teruhiko Yoshida, Akira Kawai

研究成果: Article査読

25 被引用数 (Scopus)

抄録

Bone and soft tissue sarcomas (BSTSs) are rare malignant tumors of mesenchymal origin. Although BSTSs frequently occur in some hereditary cancer syndromes with germline mutations of DNA repair genes, genetic factors responsible for sporadic cases have not been determined. In the present study we undertook a case-control study and analyzed possible associations between the susceptibility to BSTS and the single nucleotide polymorphisms (SNPs) in DNA repair genes. Genomic DNAs extracted from case and control peripheral blood leukocytes were genotyped by pyrosequencing. For candidate polymorphisms, we chose 50 non-synonymous missense SNPs, which we have previously been identified by resequencing 36 DNA repair genes among the Japanese population. In the first screening, we analyzed 240 cases and 685 controls and selected six SNPs at the significance level of P < 0.1 (Fisher's exact test). The six SNPs were further analyzed in the second genotyping on an additional set of 304 cases and 834 controls. In the joint analysis (the first and second genotyping combined) of 544 cases and 1378 controls, Cys1367Arg of the WRN gene was found to be a protective factor of BSTS (odds ratio = 0.66, 95% confidence interval = 0.49-0.88, P = 0.005). An exploratory subgroup analysis without multiple comparison adjustment suggested that the WRN-Cys1367Arg SNP is associated with soft tissue sarcomas, sarcomas with reciprocal chromosomal translocations and malignant fibrous histiocytoma.

本文言語English
ページ(範囲)333-339
ページ数7
ジャーナルCancer science
99
2
DOI
出版ステータスPublished - 2008 2月

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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