Replication study of SNP associations for colorectal cancer in Hong Kong Chinese.

BACKGROUND: Recent genome-wide association studies of colorectal cancer (CRC) have identified common single-nucleotide polymorphisms (SNPs) mapping to 10 independent loci that confer modest increased risk. These studies have been conducted in European populations and it is unclear whether these observations generalise to populations with different ethnicities and rates of CRC. METHODS: An association study was performed on 892 CRC cases and 890 controls recruited from the Hong Kong Chinese population, genotyping 32 SNPs, which were either associated with CRC in previous studies or are in close proximity to previously reported risk SNPs. RESULTS: Twelve of the SNPs showed evidence of an association. The strongest associations were provided by rs10795668 on 10p14, rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear association between CRC risk and the number of independent risk variants possessed by an individual (P=2.29 × 10(-5)). CONCLUSION: These results indicate that some previously reported SNP associations also impact on CRC risk in the Chinese population. Possible reasons for failure of replication for some loci include inadequate study power, differences in allele frequency, linkage disequilibrium structure or effect size between populations. Our results suggest that many associations for CRC are likely to generalise across populations.

Assessment of chemosensitivity in patients with osteogenic sarcoma using the doxorubicin binding assay.

BACKGROUND AND OBJECTIVES: Assessment of chemosensitivity in patients with osteosarcoma may help identify those with resistance to chemotherapy. In this study, we investigated the clinical value of the doxorubicin binding assay in its ability to identify patients with drug resistance. METHODS: We tested tumor tissue samples obtained at biopsy of 24 patients with high-grade osteosarcoma aged 9-61 years (mean 19.2) for sensitivity to doxorubicin, using the doxorubicin binding assay. Tumor excision was performed in these patients after neoadjuvant chemotherapy. Chemotherapy response was judged on the basis of tumor necrosis achieved and was compared with doxorubicin sensitivity in each of these patients. RESULTS: Doxorubicin sensitivity was good in 15 and poor in 9 of 24 patients studied. In patients with good sensitivity (n = 15), 9 (60%) exhibited a good response to chemotherapy while response was poor in 6. In patients with poor sensitivity (n = 9), response to chemotherapy was poor in all 9 (100%) patients and 7 (77.8%) of these patients developed metastatic disease within a mean period of 5.2 months, resulting in two deaths. The results were statistically significant at P = 0.0193. CONCLUSIONS: Doxorubicin binding assay may be useful in identifying patients with inherent resistance to chemotherapy. As the outcome of patients showing resistance to doxorubicin is poor, innovative strategies may need to be developed for this group of patients.