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

Turrent 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

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Abstract

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.

Original languageEnglish
Pages (from-to)333-339
Number of pages7
JournalCancer Science
Volume99
Issue number2
DOIs
Publication statusPublished - 2008 Feb

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Sarcoma
Single Nucleotide Polymorphism
Japan
Bone and Bones
DNA Repair
Genes
Hereditary Neoplastic Syndromes
Malignant Fibrous Histiocytoma
Genetic Translocation
Germ-Line Mutation
Case-Control Studies
Leukocytes
Odds Ratio
Confidence Intervals
DNA
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Association of a missense single nucleotide polymorphism, Cys1367Arg of the WRN gene, with the risk of bone and soft tissue sarcomas in Japan. / Nakayama, Turrent Robert; Sato, Yasunori; Masutani, Mitsuko; Ogino, Hideki; Nakatani, Fumihiko; Chuman, Hirokazu; Beppu, Yasuo; Morioka, Hideo; Yabe, Hiroo; Hirose, Hiroshi; Sugimura, Haruhiko; Sakamoto, Hiromi; Ohta, Tsutomu; Toyama, Yoshiaki; Yoshida, Teruhiko; Kawai, Akira.

In: Cancer Science, Vol. 99, No. 2, 02.2008, p. 333-339.

Research output: Contribution to journalArticle

Nakayama, TR, Sato, Y, Masutani, M, Ogino, H, Nakatani, F, Chuman, H, Beppu, Y, Morioka, H, Yabe, H, Hirose, H, Sugimura, H, Sakamoto, H, Ohta, T, Toyama, Y, Yoshida, T & Kawai, A 2008, 'Association of a missense single nucleotide polymorphism, Cys1367Arg of the WRN gene, with the risk of bone and soft tissue sarcomas in Japan', Cancer Science, vol. 99, no. 2, pp. 333-339. https://doi.org/10.1111/j.1349-7006.2007.00692.x
Nakayama, Turrent Robert ; Sato, Yasunori ; Masutani, Mitsuko ; Ogino, Hideki ; Nakatani, Fumihiko ; Chuman, Hirokazu ; Beppu, Yasuo ; Morioka, Hideo ; Yabe, Hiroo ; Hirose, Hiroshi ; Sugimura, Haruhiko ; Sakamoto, Hiromi ; Ohta, Tsutomu ; Toyama, Yoshiaki ; Yoshida, Teruhiko ; Kawai, Akira. / Association of a missense single nucleotide polymorphism, Cys1367Arg of the WRN gene, with the risk of bone and soft tissue sarcomas in Japan. In: Cancer Science. 2008 ; Vol. 99, No. 2. pp. 333-339.
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AU - Nakayama, Turrent Robert

AU - Sato, Yasunori

AU - Masutani, Mitsuko

AU - Ogino, Hideki

AU - Nakatani, Fumihiko

AU - Chuman, Hirokazu

AU - Beppu, Yasuo

AU - Morioka, Hideo

AU - Yabe, Hiroo

AU - Hirose, Hiroshi

AU - Sugimura, Haruhiko

AU - Sakamoto, Hiromi

AU - Ohta, Tsutomu

AU - Toyama, Yoshiaki

AU - Yoshida, Teruhiko

AU - Kawai, Akira

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N2 - 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.

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