Table 1.
Summary of altered genetic polymorphisms and variants of key genes in cancer pathways, changing susceptibility to prostate cancer across race
| Gene | Cancer Pathway | Racial Heterogeneity of Gene Mutations and Expressions | References |
|---|---|---|---|
| Serum Androgen | - AA shown to have higher mean serum testosterone levels (about 15%) than CA | 17, 18 | |
| AR | Gene transcription | CAG and GGC repeat length | |
| - expression of AR protein was 22% higher in the benign prostate and 81% higher in PCa in AA than CA | 23 | ||
| - AA men tend to have significantly shorter repeats than CA men | 24, 31, 32 | ||
| - among low risk of PCa (normal PSA and prostate examination), nearly twice as many AA have a CAG repeat length less than 20 compared with CA men | |||
| SRD5A2 | Androgen conversion (DHT) | TA repeat alleles | |
| - present in only AA, not in CA or Asian | 155 | ||
| A49T variants | |||
| - increase DHT production, particularly in AA and Hispanic | 39 | ||
| CYP17 | Androgen synthesis | A1 and A2 alleles | |
| - polymorphisms may have a role in PCa susceptibility in AA but not CA | 52 | ||
| - A2 allele was slightly less frequent in AA versus CA, but another study had the opposite finding | 39 | ||
| CYP3A4 | Androgen deactivation | G variant | |
| - considerably more common among AA (>50%) than CA (<10%), Hispanic, or Asian | 58–61 | ||
| - in CA, associated with a higher clinical grade and stage, especially if PCa was diagnosed at an older age (≥ 64), and is predictive of progression | |||
| - in AA strongly associated with PCa that had aggressive characteristics at diagnosis | 67 | ||
| - after prostatectomy, increasing copies were found to be associated with worse progression-free survival among CA but had virtually no impact on AA | 71 | ||
| IGF-1 and IGFB-3 | Growth factors | - AA men have been found to have higher IGF-1 and lower IGFB-3 levels | 72 |
| EGFR | Growth factor receptor/Signal transduction | CA repeat length | |
| - the longer allele is significantly more common in Asian individuals and is associated with an 80% reduction in EGFR protein expression compared with the shorter allele | 82, 83 | ||
| - EGFR overexpression in PCa is more common in AA (45%) than CA (18%) | 80, 86 | ||
| - no correlation found in another study | 87 | ||
| TK domain | |||
| - 4 novel missense mutations found: 3 in Koreans and 1 in CA but none in AA | 88 | ||
| EphB2 | Tyrosinne kinase receptor/Tumor suppressor | K1019X mutation | 93 |
| - higher in AA with a family history of PCa (15.3%) than CA controls (1.7%) | |||
| - associated with increased risk for PCa in AA with a family history | |||
| - risk for PCa was increased 3-fold among AA who carried at least one copy of the allele and had a family history of PCa | |||
| BCL-2 | Apoptosis | - linkage between increased cancer proliferation and BCL-2 positively seen in prostate tumors in AA but not in CA | 94 |
| MDM2 | p53 regulator | - expression was significantly greater in CA than AA patients (78% CA, 45% AA) | 110 |
| short arm of chromosome 8 (8p22-23) | (potential) Tumor suppressor | short arm deletion | |
| - conflicting findings | 128 – 130 | ||
| miRNAs | Regulation of transcription and translation | let-7c and miR30c | |
| - higher let-7c and 30c expression in PCa tissue in AA than in CA, but only let-7c remained statistically significant after normalization | D. Hatcher and P. Lee, unpublished data | ||
| MSR1 | common MSR1 sequence variants | ||
| - in AA, germline mutations was associated with an increased risk of PCa | 152 | ||
| - in CA, five common sequence variants had significantly different allele frequencies among men with PCa compared with unaffected men, with each, except INDEL7, associated with an elevated risk for PCa | 153 | ||
| - in AA, Asp174Tyr mutation is nearly twice as common among PCa patients compared with controls; however, none were associated with a significantly increased risk of PCa | 112 |