Carcinogenesis, Vol. 23, No. 2, 257-264,
February 2002
© 2002 Oxford University Press
MOLECULAR EPIDEMIOLOGY |
Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer
1 Department of Urology and
2 Medical Information Science, Akita University School of Medicine, Akita 010-8543 and
3 Department of Urology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Abstract
Cyclin D1 is believed to play an important role in the genesis and/or progression of transitional cell cancer (TCC) of the urinary bladder. Cyclin D1 gene (CCND1) mRNA is alternatively spliced to produce two transcripts, and the splicing pattern may be modulated by a G to A single nucleotide polymorphism within the splice donor site of exon 4. This study was conducted to explore the association between the polymorphism and the susceptibility to and disease status of TCC of the bladder in 222 cases and 317 native Japanese controls. The relationship between the CCND1 polymorphism and the mRNA splicing pattern in TCC cells was evaluated by semi-quantitative reverse-transcription PCR. The CCND1 A allele was more frequently observed in the TCC group than the control group (P = 0.032) with a significant difference in the genotype frequency between the two groups (P = 0.029). The AA genotype was associated with a significantly higher risk of TCC compared with the AG+GG genotypes (adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) = 1.09–2.84, P = 0.022). This association was observed more significantly in nonsmoking cases (aOR = 2.53; 95% CI = 1.28–4.51, P = 0.008). Looking at tumor grade, the presence of the A allele was associated with higher grade (= grade 3) tumors with a gene dosage effect (aOR = 1.77, CI = 1.16–2.69, P = 0.008). In tumor stage, although not significant, the AA + AG genotypes tended to be more frequently observed in cases with T1-4 tumors than those with Ta tumors (aOR = 1.94, 95% CI = 0.98–3.82, P = 0.057). The genotype seemed to influence the two alternatively spliced forms of the CCND1 mRNA because the ratio of the CCND1 transcript-b/transcript-a was significantly higher in cases with the AA genotype compared with those with the AG + GG genotypes. These data suggest that the CCND1 variant A allele may be associated with an increased risk of TCC of the bladder, especially in men without a history of smoking, and it may also have an effect on its disease status.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. A. Mason, E. V. Morlock, M. R. Karagas, K. T. Kelsey, C. J. Marsit, A. R. Schned, and A. S. Andrew EGFR pathway polymorphisms and bladder cancer susceptibility and prognosis Carcinogenesis, July 1, 2009; 30(7): 1155 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Pabalan, B. Bapat, L. Sung, H. Jarjanazi, O. Francisco-Pabalan, and H. Ozcelik Cyclin D1 Pro241Pro (CCND1-G870A) Polymorphism Is Associated with Increased Cancer Risk in Human Populations: A Meta-Analysis Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2773 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-J. Chen, Y.-S. Ho, H.-R. Guo, and Y.-J. Wang Rapid Activation of Stat3 and ERK1/2 by Nicotine Modulates Cell Proliferation in Human Bladder Cancer Cells Toxicol. Sci., August 1, 2008; 104(2): 283 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Bewick, M. S.C. Conlon, and R. M. Lafrenie Polymorphisms in XRCC1, XRCC3, and CCND1 and Survival After Treatment for Metastatic Breast Cancer J. Clin. Oncol., December 20, 2006; 24(36): 5645 - 5651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Probst-Hensch, C.-L. Sun, D. V. D. Berg, M. Ceschi, W.-P. Koh, and M. C. Yu The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study Carcinogenesis, December 1, 2006; 27(12): 2475 - 2482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Huang, M. R. Spitz, J. Gu, J.J. Lee, J. Lin, S. M.Lippman, and X. Wu Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions Carcinogenesis, October 1, 2006; 27(10): 2034 - 2037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tsuchiya, L. Wang, H. Suzuki, T. Segawa, H. Fukuda, S. Narita, M. Shimbo, T. Kamoto, K. Mitsumori, T. Ichikawa, et al. Impact of IGF-I and CYP19 Gene Polymorphisms on the Survival of Patients With Metastatic Prostate Cancer J. Clin. Oncol., May 1, 2006; 24(13): 1982 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ceschi, C.-L. Sun, D. Van Den Berg, W.-P. Koh, M. C. Yu, and N. Probst-Hensch The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore Carcinogenesis, August 1, 2005; 26(8): 1457 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Spitz, X. Wu, and G. Mills Integrative Epidemiology: From Risk Assessment to Outcome Prediction J. Clin. Oncol., January 10, 2005; 23(2): 267 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. O. Shu, D. B. Moore, Q. Cai, J. Cheng, W. Wen, L. Pierce, H. Cai, Y.-T. Gao, and W. Zheng Association of Cyclin D1 Genotype with Breast Cancer Risk and Survival Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 91 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fu, C. Wang, Z. Li, T. Sakamaki, and R. G. Pestell Minireview: Cyclin D1: Normal and Abnormal Functions Endocrinology, December 1, 2004; 145(12): 5439 - 5447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sanyal, F. Festa, S. Sakano, Z. Zhang, G. Steineck, U. Norming, H. Wijkstrom, P. Larsson, R. Kumar, and K. Hemminki Polymorphisms in DNA repair and metabolic genes in bladder cancer Carcinogenesis, May 1, 2004; 25(5): 729 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Listgarten, S. Damaraju, B. Poulin, L. Cook, J. Dufour, A. Driga, J. Mackey, D. Wishart, R. Greiner, and B. Zanke Predictive Models for Breast Cancer Susceptibility from Multiple Single Nucleotide Polymorphisms Clin. Cancer Res., April 15, 2004; 10(8): 2725 - 2737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Le Marchand, A. Seifried, A. Lum-Jones, T. Donlon, and L. R. Wilkens Association of the Cyclin D1 A870G Polymorphism With Advanced Colorectal Cancer JAMA, December 3, 2003; 290(21): 2843 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Cortessis, K. Siegmund, S. Xue, R. K. Ross, and M. C. Yu A case-control study of cyclin D1 CCND1 870A->G polymorphism and bladder cancer Carcinogenesis, October 1, 2003; 24(10): 1645 - 1650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Qiuling, Z. Yuxin, Z. Suhua, X. Cheng, L. Shuguang, and H. Fengsheng Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population Carcinogenesis, September 1, 2003; 24(9): 1499 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Solomon, Y. Wang, S. R. Fox, T. C. Lambeck, S. Giesting, Z. Lan, A. M. Senderowicz, and E. S. Knudsen Cyclin D1 Splice Variants: DIFFERENTIAL EFFECTS ON LOCALIZATION, RB PHOSPHORYLATION, AND CELLULAR TRANSFORMATION J. Biol. Chem., August 8, 2003; 278(32): 30339 - 30347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yu, W. Lu, W. Tan, D. Xing, G. Liang, X. Miao, and D. Lin Lack of Association between CCND1 G870A Polymorphism and Risk of Esophageal Squamous Cell Carcinoma Cancer Epidemiol. Biomarkers Prev., February 1, 2003; 12(2): 176 - 176. [Full Text] [PDF]
|
|