Cyclin D1 A870G polymorphism in Brazilian colorectal cancer patients

被引：12
作者：
Forones N.M. [1 ,2 ]
De Lima J.M. [1 ]
De Souza L.G. [1 ]
Da Silva I.D.C.G. [1 ]
机构：
[1] Oncology Group/Gastroenterology Division, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo
[2] Disciplina de Gastroenterologia Clínica, Universidade Federal de Sao Paulo, São Paulo CEP: 04023-900, R. Botucatu 740
来源：
Journal of Gastrointestinal Cancer | 2008年 / 39卷 / 1-4期
基金：
巴西圣保罗研究基金会;
关键词：
A870G cyclin D1; CCND; 1; Colorectal cancer; Cyclin D1; Polymorphism;
D O I：
10.1007/s12029-009-9057-z
中图分类号：
学科分类号：
摘要：
Introduction: Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle. A common G to A polymorphism in the CCND1 gene is implicated on the splicing of the CCND1 transcript, and this protein may be associated to a deregulated cell proliferation. Aim: Correlate the polymorphism A870G of CCND1 to the risk of colorectal cancer (CRC), to environmental risk factors and clinical aspects in Brazilian patients. Patients and Methods: One hundred twenty-three Brazilian patients with colorectal cancer were matched by age and sex to 120 healthy individuals. PCR-RFLP was performed to investigate the A870G CCND1 genotype. Results: Between the cases 70 were men, the mean age was 62.6 years, 74.78% were stage II or III, and 91% were well or moderately differentiated. The patients were followed for a mean time of 37.22 months. The frequency of ethanol and fat intake was similar among the groups. Patients with a family history of CRC had a higher frequency of CRC compared with the controls (OR 4.16, CI 1.89-9.16). There was no difference in the frequency of the alleles A (43.8% versus 43.9%) and G (56.3% versus 56.1%) in the groups. In analysis of both control and cancer group, the influence of sex, smoking, alcohol, fiber, or meat intake did not differ significantly according to CCND1 genotype. The genotype AA or AG was associated with an increased risk of CRC (OR 3.63 CI 1.25-10.5) in patients with a family history of cancer. We did not find any association among the genotypes and localization of the tumor or prognosis. Although a difference on age onset of the tumor and genotype was not observed, patients with GG genotype had a mean 8 years lower than the others. This genotype was also associated to an increase risk of metastatic disease (OR 3.47, CI 1.38-8.68, p=0.024). Conclusion: We did not find a correlation among the polymorphism of CCND1 A870G and colorectal cancer risk or between this polymorphism and lifestyle habits, diet, or follow-up. GG genotype patients had an increased risk of advanced disease and between the young patients, this genotype was associated to a lower mean age. On the other hand, the genotype AA or AG had been involved to a higher risk of CRC in patients with family history of CRC. © 2009 Humana Press Inc.
引用
收藏
页码：118 / 123
页数：5
相关论文
共 27 条
[1]  
Canters for Disease Control and Prevention: US Mortality Public Use Data Tapes. 1969-2003
[2]  
Estimativas de Incidência e Mortalidade
[3]  
Boyle P., Langman J.S., ABC of colorectal cancer, BMJ, 321, pp. 805-808, (2000)
[4]  
Houlston R.S., Tomilnson I.P.M., Polymorphism and colorectal cancer tumor risk, Gastroenterology, 121, pp. 282-301, (2001)
[5]  
Arber N., Hibshoosh H., Moss S.F., Sutter T., Zhang Y., Begg M., Wang S., Weinstein I.B., Holt P.R., Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis, Gastroenterology, 110, 3, pp. 669-674, (1996)
[6]  
Arber N., Doki Y., Han E.K., Sgambato A., Zhou P., Kim N.H., Delohery T., Klein M.G., Holt P.R., Weinstein I.B., Antisense to cyclin D1 inhibits the growth and tumorigenicity of human colon cancer cells, Cancer Res, 57, pp. 1569-1574, (1997)
[7]  
Betticher D.C., Thatcher N., Altermatt H.J., Hoban P., Ryder W.D.J., Heighway J., Oncogene, 11, pp. 1005-1011, (1995)
[8]  
Weinstein I.B., Begemann M., Zhou P., Han E.K., Sgambato A., Doki Y., Arber N., Ciaparrone M., Yamamoto H., Disorders in cell circuitry associated with multistage carcinogenesis: Exploitable targets for cancer prevention and therapy, Clin Cancer Res., 3, pp. 2696-2702, (1997)
[9]  
Sawa H., Ohshima T.A., Ukita H., Murakami H., Chiba Y., Kamada H., Hara M., Saito I., Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner, Oncogene, 16, 13, pp. 1701-1712, (1998)
[10]  
Kong S., Amos C.I., Lutra R., Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer, Cancer Res, 60, pp. 249-252, (2000)
123