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. 2009 Apr 20;1(3):235–248.

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