G870A POLYMORPHISM IN THE CYCLIN D1 GENE IN COLORECTAL CANCER
Stefanovska A-M1, Josifovski T2, Panovski M2, Jasar D3, Zografski G3, Popevska Z4, Efremov GD1, Dimovski AJ1,*
*Corresponding Author: : Dr. Aleksandar J. Dimovski, Macedonian Academy of Sciences and Arts, Research Center for Genetic Engineering and Biotechnology, Av. Krste Misirkov 2, POB 428, 1000 Skopje, Republic of Macedonia; Tel: +3892-120253; Fax: +3892-115434; E-mail: aleks@manu.edu.mk *Current address: Faculty of Pharmacy, Vodnjanska 17, 1000 Skopje, Republic of Macedonia; Tel: +3892 119694; FAX: + 3892 123054; E-mail: adimovski@baba.ff.ukim.edu.mk
page: 27

RESULTS AND DISCUSSION

Patient and control subjects were found to have similar allelic frequencies of the CCND1 polymorphism (A allele 0.54 for patients and 0.51 for controls; p = 0.47) and genotypes distribution (AA 32%, AG 44%, GG 24% for patients and AA 25%, AG 51%, GG 24% for controls; p = 0.47) (Table 1). Allelic frequencies (A allele 0.54) and genotype distribution (AA 36%, AG 36%, GG 28%) of patients who were less than 60 years of age also did not differ from those of the controls (p = 0.65 and p = 0.19, respectively).

      Age and gender of patients, as well as localization or the Dukes' stage of tumors, did not influence the allelic frequencies and genotype distribution of the CCND1 polymorphism (p >0.1 in all instances). Although the number of patients was small, a statistically significant difference in CCND1 polymorphism frequencies was found when patients less than 60 years of age were analyzed in relation to the MSI status of their tumors (Table 2). Comparison of the distribution of AA and AG genotypes in this group of patients suggested that the A allele acts as a dominant trait [Odds Ratio 4.69, 95% Confidance Interval 1.02-21.54, p = 0.046].

 

 

      Our data indicate that the CCND1 polymorphism may influence the age at onset of colorectal cancer in young patients only when their tumors exhibit an MSI phenotype. This conclusion is in agreement with the initial findings of Kong et al. [14] for the influence of this variant in HNPCC kindreds, since MSI phenotype is present in almost all tumors of patients with this condition [17]. The most likely explanation for these findings is that units of the cyclin D1 regulated cell cycle control system are frequently inactivated by the MSI phenotype, thus potentiating the proliferative activity of the aberrant CCND1 protein produced from the A allele. However, such an association was not found by McKay et al. [11] and by Bala et al. [15], which further potentiates the complexity of the genetic predisposition for the development of colorectal cancer.

 

 

Table 1. Allelic frequencies and genotype distribution of the G870A polymorphism in the CCND1 gene in colorectal cancer patients and control subjects.

 

 

Patients

(n = 167)

Control

Subjects

(n = 173)

p


Alleles

              A

              G

 

0.54 (54.0)

0.46 (46.0)

 

0.51 (51%)

0.49 (49%)

 

0.47

Genotypes

              AA

              AG

              GG

 

53 (32%)

73 (44%)

41 (21%)

 

43 (25%)

88 (51%)

42 (24%)

 

0.47

 

 

Table 2. Alellic frequencies and genotype distribution of the G870A polymorphism in the CCND1 gene in colorectal cancer patients less than 60 years of age in relation to the MSI status of their tumors.

 

 

MSI

Tumors

(n = 9)

MSS

TumorsÎ

(n = 47)

p

Alleles

              A

              G

 

0.83 (83%)

0.17 (17%)

 

0.48 (48%)

0.52 (52%)

 

0.005

Genotypes

              AA

              AG

              GG

 

6 (67%)

3 (33%)

0 (0%)

 

14 (30%)

17 (36%)

16 (34%)

 

0.05

 





Number 22
VOL. 22(1), 2019
Number 22
VOL. 22, 2019 Accepted articles
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Accepted articles
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006