Prostate specific antigen (PSA) is a useful marker for screening of prostate cancer (PCa), one of the leading causes of death in the world. Here, we showed that two genetic variants in SLC45A3 and KLK3 genes are significantly associated with PSA levels in the Japanese population. The association of SLC45A3 was not known in Japanese. We showed that the more variants of these two regions subjects carry, the lower accuracy of PCa a screening with the use of PSA levels provide. Our results suggest that classifying subjects based on number of these variants may lead better screening performance for PCa. (By Chikashi Terao, http://jmg.bmj.com/content/early/2014/06/11/jmedgenet-2014-102423 )