| EGFR (Epidermal growth factor receptor) |
EGFR helps in cellular proliferation, progression, tumor cell invasion and also a target of anticancer agents for androgen-independent PCa,. Over-expresses of EGFR in PCa is more common in African American (AA) than Caucasian American (CA). EGFR inhibitors hinder the growth of both androgen dependent and independent PCa xenografts. Androgen independent, metastatic PCa and androgen ablation increases the expression of EGFR Intronic dinucleotide repeats (CA) n (range from 14 to 21 correlated with transcriptional activity) polymorphism. Longer allele of EGFR is associated with 80% reduction in EGFR protein expression than shorter allele. Three out of four missense mutations in EGFR TK domain identified as oncogenic in nature. These mutations are reported in 3 Koreans, 1 in CA but none in AA.
|
(180–186) |
| EPHB2 (Ephrin type-B receptor 2) |
Located on 1p36, and link with hereditary PCa with racially diverse family. Studies in DU145 PCa cell line suggested that it may be tumor suppressor gene. Screening of the EphB2 gene for germline polymorphisms in AA PCa identified ten sequence variants in the gene, including a common nonsense mutation and K1019X. The risk for PCa increased 3-fold among AA men who carried at least one copy of the K1019X allele and had a family history of PCa.
|
(187–189) |
| VDR (Vitamin D receptor) |
European American men have high plasma levels of the active form of vitamin D, 25-hydroxyvitamin D, which is associated with decreased risk of lethal PCa. SNP sets linked to 7 vitamin D pathway-related genes, including VDR, which are associated with PCa risk. A single VDR polymorphism, the BsmI B allele, is protective against recurrence of PCa in European American men but not in AA men. The decrease VDR signaling contributes to the greater risk of advanced or lethal PCa in AA population.
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(190–192) |
