Heritability of prostate-specific antigen and relationship with zonal prostate volumes in aging twins

Both benign prostatic hyperplasia and prostate-speciftc antigen (PSA) have been shown to increase with age and with prostate volume in men, but the in fluence of heredity on these relationships is not completely understood. Th is study has two aims: 1) to investigate the inter-relationships of age, PS A, and various zonal measurements in the prostate; and 2) to assess the imp act of heritable influences on total PSA. Eighty-four monozygotic twin pair s and 83 dizygotic twin pairs were studied, and serum total PSA, free PSA, and PSA-proportional to(1)-antichymotrypsin were measured. Their prostate v olumes [total (TV), transition zone (TZ), and peripheral zone] were quantit ated using transrectal ultrasound. Total PSA is significantly correlated wi th all zonal prostate measurements (TZ, peripheral zone, TV, and TZ/TV) and with age. When linear regression was applied, only age and TZ were retaine d in the final model. The proportion of variability in total PSA explained by these two factors, however, is below 24%. Tn contrast, estimates of heri tability show that approximately 45% of the variability in total PSA can be explained by inherited factors. Whereas age and TZ are linearly related to total PSA, their influence is much less than that of familial and genetic factors. It is uncertain whether these factors predispose also to prostate cancer or if they are independent; of those, whether they confound the accu racy of using total serum PSA level as a diagnostic tool.