The influence of the Cyclin D1 870 G>A polymorphism as an endometrial cancer risk factor.
BACKGROUND
Cyclin D1 is integral for the G1 to S phase of the cell cycle as it regulates cellular proliferation. A polymorphism in cyclin D1, 870 G>A, causes overexpression and supports uncontrollable cellular growth. This polymorphism has been associated with an increased risk of developing many cancers, including endometrial cancer.


METHODS
The 870 G>A polymorphisms (rs605965) in the cyclin D1 gene was genotyped in an Australian endometrial cancer case-control population including 191 cases and 291 controls using real-time PCR analysis. Genotype analysis was performed using chi-squared (chi2) statistics and odds ratios were calculated using unconditional logistic regression, adjusting for potential endometrial cancer risk factors.


RESULTS
Women homozygous for the variant cyclin D1 870 AA genotype showed a trend for an increased risk of developing endometrial cancer compared to those with the wild-type GG genotype, however this result was not statistically significant (OR 1.692 95% CI (0.939-3.049), p = 0.080). Moreover, the 870 G>A polymorphism was significantly associated with family history of colorectal cancer. Endometrial cancer patients with the homozygous variant AA genotype had a higher frequency of family members with colorectal cancer in comparison to endometrial cancer patients with the GG and combination of GG and GA genotypes (GG versus AA; OR 2.951, 95% CI (1.026-8.491), p = 0.045, and GG+GA versus AA; OR 2.265, 95% CI (1.048-4.894), p = 0.038, respectively).


CONCLUSIONS
These results suggest that the cyclin D1 870 G>A polymorphism is possibly involved in the development of endometrial cancer. A more complex relationship was observed between this polymorphism and familial colorectal cancer.
Ashton
Katie A
KA
Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia and Hunter Medical Research Institute, NSW, 2308, Australia. katie.ashton@studentmail.newcastle.edu.au
Proietto
Anthony
A
Otton
Geoffrey
G
Symonds
Ian
I
McEvoy
Mark
M
Attia
John
J
Gilbert
Michael
M
Hamann
Ute
U
Scott
Rodney J
RJ
D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D056741:Cyclin D; D016213:Cyclins