Carcinogenesis Advance Access published online on July 8, 2006
Carcinogenesis, doi:10.1093/carcin/bgl116
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Molecular Epidemiology/Cancer Registry, Institutes of Social and Preventive Medicine/Surgical Pathology, University Hospital Zürich, Vogelsangstr. 10, 8091 Zürich, Switzerland
* To whom correspondence should be addressed. Cyclin D1 (CCND1) regulates cellular decision between proliferation and growth arrest. Despite the functional relevance of the CCND1 A870G single nucleotide polymorphism (SNP) published results on its association with colorectal cancer (CRC) were inconsistent. We examined the association between this CCND1 genotype and CRC in the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63,000 Chinese men and women. We explored the hypothesis that inconsistency regarding the CCND1/ CRC association may be attributable to the modifying effect of additional CRC risk factors. Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort (1), we now explored if they influenced the CCND1/CRC association. In a nested case-control study within the Singapore Cohort, genomic DNA collected from 300 incident CRC cases and 1169 controls was examined for CCND1, GSTM1, GSTT1, and GSTP1 polymorphisms. Unconditional logistic regression was used to assess genotype effects on cancer risk. No main effect of CCND1 was observed, yet the CCND1 effect was influenced by ITC intake and GST genotypes. The presence of at least one CCND1 A-allele was associated with increased risk among low dietary ITC consumers (intake below median value for the cohort) with a high-activity GST profile (
Received February 2, 2006
Revised June 19, 2006
Accepted June 20, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
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
Nicole M. Probst-Hensch 1 *,
Can-Lan Sun 2,
David Van Den Berg 3,
Michela Ceschi 1,
Woon-Puay Koh 4,
and
Mimi C. Yu 2
2 The Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
3 USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
4 Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore 117597
Nicole M. Probst-Hensch, E-mail: nicole.probst{at}usz.ch
Abstract 
2 of the three GST genotypes classified non-null or high-activity) (OR=2.05, 95% confidence interval (CI) 1.10-3.82). In contrast, the presence of at least one A-allele was associated with a decreased risk among all remaining subjects (OR=0.56; 0.36-0.86) (p for interaction=0.01). Recent studies indicate that ITCs inhibit cell proliferation and cause apoptosis through pro-oxidant properties. The results of our current study on CRC and those of our previous breast cancer study (2) are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1 effect.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|