Journal Article

The effect of the cyclin D1 (<i>CCND1</i>) A870G polymorphism on colorectal cancer risk is modified by glutathione-<i>S</i>-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study

Nicole M. Probst-Hensch, Can-Lan Sun, David Van Den Berg, Michela Ceschi, Woon-Puay Koh and Mimi C. Yu

in Carcinogenesis

Volume 27, issue 12, pages 2475-2482
ISSN: 0143-3334
Published online July 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl116
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

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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, 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 (≥2 of the 3 GST genotypes classified non-null or high-activity) [odds ratio (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 are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1 effect.

Journal Article.  6365 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.