Potential Role of CCND1 G870A Genotype as a Predictor for Urothelial Carcinoma Susceptibility and Muscle-Invasiveness in Taiwan

10.4077/CJP.2011.AMM123

Hui-Hui Lin；Hung-Lung Ke；Kuang-Hung Hsiao；Chia-Wen Tsai；Wen-Jeng Wu；Da-Tian Bau；Lin-Li Chang

CCND1 G870A ； cyclin D1 ； polymorphism ； urothelial carcinoma ； bladder cancer ； upper tract urothelial cancer

The Chinese Journal of Physiology

54卷3期（2011 / 06 / 01）

196 - 202

英文

The cell cycle regulator cyclin D1 (CCND1) is thought to play a major role in the transition of cell cycle from G1 to S phase. It is known that a common CCND1 G870A genotype is associated with bladder cancer in Japan and China, but not in the Western World. There is neither a report about its role in Taiwan’s population, nor its genetic role of CCND1 G870A in another worldwide urothelial cancer, upper tract urothelial cancer (UTUC). Therefore, we aimed at investigating the role of CCND1 G870A in both bladder cancer and UTUC in Taiwanese cohorts. The CCND1 G870A genotypes of 171 (101 bladder cancer and 70 UTUC) patients and 243 control subjects were determined by PCR-RFLP and their correlation with clinical and histopathological data was evaluated. The genotype analysis results showed that CCND1 GG genotype was associated with a lower risk overall in urothelial (P=0.008, OR=0.44, 95% CI=0.24-0.81) and bladder cancer patients (P=0.008, OR=0.34, 95% CI=0.15-0.76) than those of the AA genotype. In addition, patients carrying the AG genotype had a 0.29-fold lower odds ratio of muscle-invasive cancer procession (95% CI=0.12-0.70) compared with those carrying the AA genotype in bladder cancer patients. Surprisingly, the GG genotype had a 5.88-fold higher odds ratio of muscle-invasive cancer procession (95% CI=1.08-32.01) compared with those carrying the AA genotype in UTUC. No association between any CCND1 G870A genotype and higher-grade risk was found. Our results suggest that the G allele of the CCND1 G870A polymorphism may be a potential predictive and prognostic biomarker to distinguish between bladder cancer and UTUC in Taiwan.

1. Bau, D. T.,Hsieh, Y. Y.,Wan, L.,Wang, R. F.,Liao, C. C.,Lee, C. C.,Lin, C. C.,Tsai, C. H.,Tsai, F. J.(2007).Polymorphism of XRCC1 codon Arg 399 Gln is associated with higher susceptibility to endometriosis.Chinese J. Physiol.,50,326-329.
   連結：
2. Bau, D. T.,Tsai, M. H.,Huang, C. Y.,Lee, C. C.,Tseng, H. C.,Lo, Y. L.,Tsai, Y.,Tsai, F. J.(2007).Relationship between polymorphisms of nucleotide excision repair genes and oral cancer risk in Taiwan: evidence for modification of smoking habit.Chinese J. Physiol.,50,294-300.
   連結：
3. Bau, D. T.,Wang, H. C.,Liu, C. S.,Chang, C. L.,Chiang, S. Y.,Wang, R. F.,Tsai, C. W.,Lo, Y. L.,Hsiung, C. A.,Lin, C. C.,Huang, C. Y.(2009).Single-nucleotide polymorphism of the Exo1 gene: association with gastric cancer susceptibility and interaction with smoking in Taiwan.Chinese J. Physiol.,52,411-418.
   連結：
4. Betticher, D. C.,Thatcher, N.,Altermatt, H. J.,Hoban, P.,Ryder, W. D.,Heighway, J.(1995).Alternate splicing produces a novel cyclin D1 transcript.Oncogene,11,1005-1011.
5. Burch, J.D.,Rohan, T. E.,Howe, G. R.,Risch, H. A.,Hill, G. B.,Steele, R.,Miller, A. B.(1989).Risk of bladder cancer by source and type of tobacco exposure: a case-control study.Int. J. Cancer,44,622-628.
6. Chang, L. L.,Yeh, W. T.,Yang, S. Y.,Wu, W. J.,Huang, C. H.(2003).Genetic alterations of p16INK4a and p14ARF genes in human bladder cancer.J. Urol.,170,595-600.
7. Chen, C. J.,Hsueh, Y. M.,Lai, M. S.,Shyu, M. P.,Chen, S. Y.,Wu, M. M.,Kuo, T. L.,Tai, T. Y.(1995).Increased prevalence of hypertension and long-term arsenic exposure.Hypertension,25,53-60.
8. Chou, Y. H.,Huang, C. H.(1999).Unusual clinical presentation of upper urothelial carcinoma in Taiwan.Cancer,85,1342-1344.
9. Cortessis, V. K.,Siegmund, K.,Xue, S.,Ross, R. K.,Yu, M. C.(2003).A case-control study of cyclin D1 CCND1 870A->G polymorphism and bladder cancer.Carcinogenesis,24,1645-1650.
10. Epstein, J. I.,Amin, M. B.,Reuter, V. R.,Mostofi, F. K.(1998).The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee.Am. J. Surg. Pathol.,22,1435-1448.
11. Gangwar, R.,Mittal, R. D.(1986).Association of selected variants in genes involved in cell cycle and apoptosis with bladder cancer risk in North India population.DNA Cell Biol.,29,349-356.
12. Greene, F. L.,Page, D. L.,Fleming, I. D.(2002).AJCC Cancer Staging Manual.New York:Springer-Verlag.
13. Hirao, Y.,Kim, W. J.,Fujimoto, K.(2009).Environmental factors promoting bladder cancer.Curr. Opin. Urol.,19,494-499.
14. Ito, M.,Habuchi, T.,Watanabe, J.,Higashi, S.,Nishiyama, H.,Wang, L.,Tsuchiya, N.,Kamoto, T.,Ogawa, O.(2004).Polymorphism within the cyclin D1 gene is associated with an increased risk of carcinoma in situ in patients with superficial bladder cancer.Urology,64,74-78.
15. Jemal, A.,Tiwari, R. C.,Murray, T.,Ghafoor, A.,Samuels, A.,Ward, E.,Feuer, E. J.,Thun, M. J.(2004).Cancer statistics, 2004.CA-Cancer J. Clin.,54,8-29.
16. Knudsen, K. E.,Diehl, J. A.,Haiman, C. A.,Knudsen, E. S.(2006).Cyclin D1: polymorphism, aberrant splicing and cancer risk.Oncogene,25,1620-1628.
17. Larsson, P.,Wijkstrom, H.,Thorstenson, A.,Adolfsson, J.,Norming, U.,Wiklund, P.,Onelov, E.,Steineck, G.(2003).A population-based study of 538 patients with newly detected urinary bladder neoplasms followed during 5 years.Scand. J. Urol. Nephrol.,37,195-201.
18. Lee, C. C.,Yamamoto, S.,Morimura, K.,Wanibuchi, H.,Nishisaka, N.,Ikemoto, S.,Nakatani, T.,Wada, S.,Kishimoto, T.,Fukushima, S.(1997).Significance of cyclin D1 overexpression in transitional cell carcinomas of the urinary bladder and its correlation with histopathologic features.Cancer,79,780-789.
19. Liaw, K. L.,Linet, M. S.,McLaughlin, J. K.,Yu, M. C.,Schoenberg, J. B.,Lynch, C. F.,Niwa, S.,Fraumeni, J. F., Jr.(1997).Possible relation between hypertension and cancers of the renal pelvis and ureter.Int. J. Cancer,70,265-268.
20. Linet, M. S.,Chow, W. H.,McLaughlin, J. K.,Wacholder, S.,Yu, M. C.,Schoenberg, J. B.,Lynch, C.,Fraumeni, J.F., Jr.(1995).Analgesics and cancers of the renal pelvis and ureter.Int. J. Cancer,62,15-18.
21. Mahony, J. F.,Storey, B. G.,Ibanez, R. C.,Stewart, J. H.(1977).Analgesic abuse, renal parenchymal disease and carcinoma of the kidney or ureter.Aust. N. Z. J. Med.,7,463-469.
22. McLaughlin, J. K.,Silverman, D. T.,Hsing, A. W.,Ross, R. K.,Schoenberg, J. B.,Yu, M. C.,Stemhagen, A.,Lynch, C. F.,Blot, W. J., Fraumeni, J. F., Jr.(1992).Cigarette smoking and cancers of the renal pelvis and ureter.Cancer Res.,52,254-257.
23. Mellemgaard, A.,Carstensen, B.,Norgaard, N.,Knudsen, J. B.,Olsen, J. H.(1993).Trends in the incidence of cancer of the kidney, pelvis, ureter and bladder in Denmark 1943-88.Scand. J. Urol. Nephrol.,27,327-332.
24. Reznikoff, C. A.,Sarkar, S.,Julicher, K. P.,Burger, M. S.,Puthenveettil, J. A.,Jarrard, D. F.,Newton, M. A.(2000).Genetic alterations and biological pathways in human bladder cancer pathogenesis.Urol. Oncol.,5,191-203.
25. Rogers, S.,Wells, R.,Rechsteiner, M.(1986).Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis.Science,234,364-368.
26. Sanyal, S.,Festa, F.,Sakano, S.,Zhang, Z.,Steineck, G.,Norming, U.,Wijkstrom, H.,Larsson, P.,Kumar, R.,Hemminki, K.(2004).Polymorphisms in DNA repair and metabolic genes in bladder cancer.Carcinogenesis,25,729-734.
27. Sgambato, A.,Migaldi, M.,Faraglia, B.,De Aloysio, G.,Ferrari, P.,Ardito, R.,De Gaetani, C.,Capelli, G.,Cittadini, A.,Trentini, G.P.(2002).Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome.Int. J. Cancer,97,671-678.
28. Shin, K. Y.,Kong, G.,Kim, W. S.,Lee, T. Y.,Woo, Y. N.,Lee, J. D.(1997).Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers.Brit. J. Cancer,75,1788-1792.
29. Stacey, D.W.(2003).Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells.Curr. Opin. Cell Biol.,15,158-163.
30. Suwa, Y.,Takano, Y.,Iki, M.,Takeda, M.,Asakura, T.,Noguchi, S.,Masuda, M.(1998).Cyclin D1 protein overexpression is related to tumor differentiation, but not to tumor progression or proliferative activity, in transitional cell carcinoma of the bladder.J. Urol.,160,897-900.
31. Wang, L.,Habuchi, T.,Takahashi, T.,Mitsumori, K.,Kamoto, T.,Kakehi, Y.,Kakinuma, H.,Sato, K.,Nakamura, A.,Ogawa, O.,Kato, T.(2002).Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer.Carcinogenesis,23,257-264.
32. Williams, C. B.,Mitchell, J. P.(1973).Carcinoma of the ureter-a review of 54 cases.Brit. J. Urol.,45,377-387.
33. Yang, C. H.,Hung, W. C.,Wang, S. L.,Kang, W. Y.,Chen, W. T.,Huang, Y. C.,Su, Y. C.,Chai, C. Y.(2008).Immunoexpression and prognostic role of hTERT and cyclin D1 in urothelial carcinoma.APMIS,116,309-316.
34. Yuan, L.,Gu, X.,Shao, J.,Wang, M.,Zhu, Q.,Zhang, Z.(2010).Cyclin D1 G870A polymorphism is associated with risk and clinicopathologic characteristics of bladder cancer.DNA Cell Biol.,29,611-617.

1. Yang, Chuan-Wei,Liu, Chiu-Shong,Lin, Wen-Yuan,Lin, Chih-Hsueh,Lin, Cheng-Chieh,Li, Tsai-Chung,Li, Chia-Ing,Ho, Chien-Yi,Bau, Da-Tian(2012).Influence of Adiponectin Gene Polymorphisms on Adiponectin Serum Level and Insulin Resistance Index in Taiwanese Metabolic Syndrome Patients.中國生理學雜誌,55(6),405-411.
2. Ying, Tsung-Ho,Wang, Paulus S.,Tsai, Chia-Wen,Shui, Hao-Ai,Shih, Liang-Chun,Pan, Sin-Bao,Huang, Chung-Yu,Hsieh, Yi-Hsien,Ho, Chien-Yi,Chen, Ya-Chien,Chen, Chang-Peng,Chang, Wen-Shin,Bau, Da-Tian(2013).The Joint Effect of hOGG1 Genotype and Smoking Habit on Endometriosis in Taiwan.中國生理學雜誌,56(5),263-268.
3. Zhang, Jinhu,Yue, Limin,Yuan, Dongzhi,Yu, Haili,Liu, Fang,He, Yaping,Gao, Xiaoping(2013).Effects of Expression of Exogenous Cyclin G1 on Proliferation of Human Endometrial Carcinoma Cells.中國生理學雜誌,56(2),83-89.