Although a causal role of genetic alterations in human disease such as cancer is well established, it is still unclear whether dietary fat can modulate cancer risk in a predisposed population. Omega-3 and omega-6 polyunsaturated fatty acids (PUFA) are essential fatty acids: mammals can neither synthesize them de novo nor interconvert them; therefore, they have to be taken in from diet. Homo sapiens historical diet is estimated to have an omega-6: 3 PUFA ratio of 1: 1.Current Western diets, however, have omega-6: 3 ratios of 20 and sometimes as high as 50.Diet has also been changing rapidly in Chinese population during the last three decades in terms of fat quantity and quality. Interestingly, prostate cancer occurs at a much higher frequency in the Western than Asian countries, whereas asymptomatic occult prostate cancer with genetic mutations has similar prevalence worldwide. We used transgenic/knockout animals and cell culture models to determine the influence of dietary fat on prostate cancer risk. We found that omega-3 PUFA suppresses and omega-6 accelerates prostate cancer progression and the ratio of omega-6 to 3 is important for effective tumor suppression. Modulation of prostate cancer development by PUFA is mediated in part through Bad-dependent apoptosis. Our study highlights the importance of gene-diet interactions in prostate cancer.