Distinct Genomic Alterations in Prostate Cancers in Chinese and Western Populations Suggest Alternative Pathways of Prostate Carcinogenesis

Abstract

Prostate cancer is significantly more common in Western men than in Asian men, but the basis for this difference remains unknown. Because genomic studies of Asian prostate cancer are very limited, we used a genome-wide approach to reveal the genomic alterations in Chinese prostate cancers. We found a significant reduction in the frequency of certain somatic genomic changes that are commonly found in Western prostate cancers, including the 21q22.2-22.3 deletion, which involves the TMPRSS2:ERG fusion gene, and 10q deletion, which causes PTEN inactivation. Array results were confirmed by PCR-based molecular copy-number counting in selected samples. The different frequencies of these genomic changes were further evaluated by fluorescent in situ hybridization and immunohistochemistry analyses of tissue microarray samples. These alterations might be key genetic changes underlying the regional/ethnic difference in clinical incidence and might be induced by specific environmental and/or genetic risk factors that Western men are exposed to. Our findings suggest that tumors arise in Western and Chinese populations by alternative pathogenetic mechanisms. Cancer Res; 70(13); 5207-12. ©2010 AACR.

Prostate cancer: an emerging threat to the health of aging men in Asia

“…Other countries in Asia, including Japan (12.6/ 10 5 PY, 114th), Korea (7.6/10 5 PY, 134th) and Vietnam (2.8/10 5 PY, 161st), were also reported as having low incidence rates. 3 Such a large difference in the prostate cancer incidence rate between North America and Asia cannot be entirely explained by variations in diet, race and environmental factors, 4,5 and this fact is a cause of concern for many researchers.…”

TMPRSS2-ERG gene fusion in prostate cancer

“…Mosquera et al 26 examined 100 prostate biopsy specimens from United States patients and reported that non-Caucasian patients were less likely to have a positive TMPRSS2-ERG fusion status than Caucasion patients. These genetic differences may underlie the regional/ethnic differences in clinical incidence and might be induced by specific environmental and/or genetic risk factors 27 . The TMPRSS2-ERG gene fusion is an early event in carcinogenesis and absent in benign prostatic hyperplasia (BPH) and proliferative inflammatory atrophy (PIA).…”

Prostate cancer research in China

“…These differences may be further utilized in exploring the unique Chinese mechanism upon tumour onset and progression, as a study has confirmed a possible alternative path of carcinogenesis in gene fusion and PTEN inactivation. 18 The occurrence of rearrangements has been explained by the following genomic, cellular and environmental changes: spatial proximity, cellular stress, inappropriate repair or recombination, and DNA sequence and chromatin features. 19 The differences between Chinese and Western patients may be explained by the difference in one or more of these changes.…”