Abstract
Background: Genetics and epidemiological studies have shown that genes and environment interaction play strong roles in prostate cancer etiology. We have already shown that higher UV exposure, higher serum vitamin D, and lower skin pigmentation inversely associated with the risk of prostate cancer in African-American.
Methods: In order to explore the relationship between Vitamin D receptor (VDR) polymorphisms and prostate cancer risk in African American men; 91 affected African American men with histologically diagnosed adenocarcinoma of the prostate, PSA of > 2.5 ng/ml and a positive digital rectal exam have been recruited. Ninety-one age and ethnicity matched controls have been also recruited.
Genomic DNA was extracted from blood sample of each case and control subjects.
Nine primers were designed for amplification of 9 different axons in VDR gene. DNA fragments from all samples were amplified using PCR reaction. In order to investigate the existence of heteroduplex, PCR products denatured and using denaturing high performance liquid chromatography (DHPLC) technique heteroduplex analysis on the Wave system was performed. Those samples demonstrating heteroduplex peaks were sequenced using an ABI 377 DNA sequencer.
Results: Seven polymorphisms in VDR sequence were confirmed after sequencing. SNPs 132G>A, 332 G>A, 83 G>A, invs9-286C>T, 122 A>G, and invs10-49G>T are located in non-coding region. 209 T>C SNP is located in coding region. However this SNP is anonymous as previously reported. 332G>A, 83G>A, and invs9-286C>T SNPs showed strong negative association with prostate cancer risk (p< 0.05). 132G>A, 209T/C, and IVS10-49G>T showed direct association with risk of prostate cancer but statistically is not significant.
Using Binary Logistic Regression Model confirmed that 332G>A, 83G>A, and invs9-286C>T SNPs are good predictor of protection against prostate cancer. Whereas having SNP 209T>C is strong indicator of risk of prostate cancer.
Conclusion: It is possible that genetic variants may mediate prostate cancer risk via a mechanism involving availability of 1, 25(OH)2 D. Vitamin D protects against risk of prostate cancer. UV exposure, good vitamin D diet, and lighter skin along with advantageous VDR polymorphism as modulators of vitamin D can improve this protection.
We are in the process of assessment of analysis the interaction between other genes involved in vitamin D metabolism and environmental factors.
Our results require further corroboration in large statistically powerful sample collections.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2798.
- ©2010 American Association for Cancer Research
Volume 70, Issue 8 Supplement
