Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment.
Abstract
Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (<i>MAST3</i>, p = 6.9×10<sup>-7</sup> and <i>GAB2</i>, p = 2.0×10<sup>-6</sup>). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-<i>versus</i> treatment for the initial management of patients with low-risk PC.
EDRN PI Authors
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Medline Author List
- Amling CL
- Arnold R
- Banionyte D
- Barocas DA
- Barsa D
- Benfante N
- Bianco FJ
- Boileau L
- Brittain K
- Byrne N
- Carroll PR
- Carter HB
- Catalona WJ
- Chan JM
- Chow K
- Cookson MS
- Cooley LF
- Cooper PR
- Cooperberg MR
- Corcoran NM
- Costello AJ
- Cowan JE
- Dall'Era MA
- Dallmer JR
- Delfin M
- Dhondt CR
- Eastham JA
- Ehdaie B
- Emeka AA
- Evans CP
- Farriester S
- Finelli A
- Fleshner NE
- Flynn T
- Garza S
- Gaylis FD
- Goldenberg SL
- Gordetsky JB
- Gotwald P
- Gregg JR
- Helenowski I
- Helfand BT
- Hemken E
- Higano CS
- Jiang Y
- Kachuri L
- Karnes RJ
- Kim J
- Kirwen N
- Klein EA
- Klotz LH
- Koch M
- Kolb S
- Komisarenko M
- Kundu SD
- Lancki N
- Landis T
- Lin DW
- Loblaw A
- Loeb S
- Logothetis CJ
- Lopez IH
- Mamawala M
- Mamedov A
- Marks LS
- Martin R
- Martinez A
- McBride D
- Meyers TJ
- Morgan TM
- Nelson JB
- Newcomb LF
- Patil D
- Pavlovich CP
- Pera T
- Perez CA
- Petkewicz J
- Phares C
- Rais-Bahrami S
- Roobol MJ
- Sanda MG
- Scherr DS
- Scholtens DM
- Siddiqui J
- Spillane M
- Stadler WM
- Stanford JL
- Steele P
- Stockdale J
- Stratton KL
- Taneja SS
- Venderbos LDF
- Vesprini D
- Vij A
- Witte JS
- Wu E
- Xu J