Pharmacogenomic studies of patients with metastatic colorectal carcinoma receiving chemotherapy in Taiwan

Wei-Shu Wang, M.D., Ph.D.

National Yang-Ming University School of Medicine, and Department of Medicine, National Yang-Ming University Hospital, Taiwan

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality in Taiwan and its incidence has increased steadily over the last few decades. Chemotherapy is effective for treating metastatic CRC, and the optimization of treatment outcome is very important.

Ethnic differences have profound influence in chemotherapy for CRC patients. For example, the prevalence of homozygous triple-repeat polymorphism in TSER was twice as common in Chinese populations, which accounts for an impaired response to fluoropyrimidine regimens. With regard to genes involved in the NER pathway, a remarkably lower prevalence of ERCC1 codon 118 T allele variants and XPD Gln751 allele variants have been found in Asian populations, which may account for increased susceptibility to platinum-based chemotherapy.

In addition, it has been shown that Asian populations have a lower prevalence of GSTP1 Val105 allele variants, implicated that Asian populations might have a better detoxification pathway. Furthermore, the UGT1A1*28 polymorphism is rare in Asian populations, leading to decreased risk of severe neutropenia after being treated with irinotecan.

Up to date, no randomized study has been conducted to compare the outcome of chemotherapy in different racial populations. Whether these polymorphisms may lead to altered treatment outcome in Asian patients warrants further studies.