| Autor: |
Ramachandran, Sudarshan, Hoban, Paul R., Ichii-Jones, Fumiyo, Pleasants, Lisa, Ali-Osman, Francis, Lear, John T., Smith, Andrew G., Bowers, Bill, Jones, Peter W., Fryer, Anthony A., Strange, Richard C. |
| Zdroj: |
Pharmacogenetics; August 2000, Vol. 10 Issue: 6 p545-556, 12p |
| Abstrakt: |
We previously described associations between basal cell carcinoma (BCC) numbers and allelic variants at loci that mediate host response to ultraviolet radiation (UV). These associations were largely exerted in cases with the multiple presentation phenotype (MPP). This phenotype describes patients who present at their first or a later presentation with a cluster of BCC (2–10 new BCC). Remaining BCC cases have the single presentation phenotype (SPP) and may develop more than one BCC but only have single new lesions at any presentation. We proposed that the MPP cases comprise a high-risk group as they suffer significantly more lesions than SPP cases. We are attempting to determine, in the total BCC case group and subgroups, how many genes influence BCC numbers and their relative importance. In this study, we assessed the influence of two further candidates, glutathione S-transferase GSTP1and cyclin D1 (CCND1), on tumour numbers in a total group of 457 patients comprising MPP and SPP cases. The relative importance of these genes in comparison with occupational UV exposure and host response (skin type) was also considered. We found that the frequencies of GSTP1genotypes based on the Ile105and Val105-expressing alleles and CCND1 AA, AG, GGgenotypes were similar in MPP and SPP cases and that there were no significant associations between GSTP1or CCND1genotypes and BCC numbers in the total or SPP groups. However, in the MPP cases, GSTP1Val105/Val105was associated with more tumours (P0.05, reference GSTP1Ile105/Ile105). Inclusion of skin type and indoor/outdoor occupation in the negative binomial regression models did not alter the associations of these genotypes with tumour numbers. DNA from 258 cases was analysed to identify GSTP1A(Ile105-Ala114), GSTP1B(Val105-Ala114), GSTP1C(Val105-Val114) and GSTP1D(Ile105-Val114). In SPP cases, there was no association between BCC numbers and GSTP1 BB, though the association with GSTP1 BCapproached significance (P0.09). In MPP cases, GSTP1 BCwas associated with BCC numbers (P0.03). We also found that the interaction term, GSTP1Val105/Val105with CCND1 AA, was associated with BCC numbers in the total (P0.001) and MPP (P0.006) but not SPP (P0.68) groups. In a stepwise model including GSTP1Val105/Val105, CCND1 AAand their interaction terms as well as GSTM1, GSTT1and CYP2D6genotypes, skin type 1 and gender, the combination of genotypes was the best predictor of BCC numbers. These data suggest that study of further genes involved in cell-cycle control and protection from oxidative stress will be useful, particularly in high-risk subgroups. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
