Ru Yin Tsai

Association Between DNA Repair Gene ATM Polymorphisms and Oral Cancer Susceptibility

The ataxia‐telangiectasia mutated (ATM) is thought to play a major role in the caretaking of the overall genome stability, and its mutations have been implicated in human cancers. However, the role of ATM polymorphisms in oral carcinogenesis is largely unexplored. Thus, the polymorphic variants of ATM were first investigated for their association with oral cancer susceptibility.

Clarification of the phenotypic characteristics and anti-tumor activity of Hedyotis diffusa.

Hedyotis diffusa Willd. (Rubiaceae) is an important folk herb used to prevent and cure hepatitis and liver cancer in Taiwan. For differentiation of H. diffusa from counterfeits, macroscopic and microscopic characters of H. diffusa, H. corymbosa and H. tenelliflora were examined in this study. According to Trypan blue exclusion assay and Western blot analysis, H. diffusa had a significant inhibition of cell growth and induction of cell apoptosis in COLO 205 (colon cancer), Hep 3B (hepatocellular carcinoma) and H460 (lung cancer) cell lines. This study also used high-performance liquid chromatography (HPLC) to determine the quality control of H. diffusa. The HPLC data showed that ursolic and oleanolic acid are the components of the H. diffusa, consisting of approximately 4.66-4.80% and 1.86-1.96%, respectively. Our study also demonstrated that ursolic acid has significant anti-tumor activity in COLO 205, Hep 3B and H460 cancer cells.

Association of Alpha B-Crystallin Genotypes with Oral Cancer Susceptibility, Survival, and Recurrence in Taiwan

Background Alpha B-crystallin (CRYAB) is a protein that functions as “molecular chaperone” in preserving intracellular architecture and cell membrane. Also, CRYAB is highly antiapoptotic. Abnormal CRYAB expression is a prognostic biomarker for oral cancer, while its genomic variations and the association with carcinogenesis have never been studied. Methodology/Finding Therefore, we hypothesized that CRYAB single nucleotide polymorphisms may be associated with oral cancer risk. In this hospital-based study, the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2 (rs2070894) polymorphisms with oral cancer in a Taiwan population was investigated. In total, 496 oral cancer patients and 992 age- and gender-matched healthy controls were genotyped and analyzed. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the oral cancer and control groups. The CRYAB C-802G G allele conferred an increased risk of oral cancer (P = 1.49×10−5). Patients carrying CG/GG at CRYAB C-802G were of lower 5-year survival and higher recurrence rate than those of CC (P<0.05). Conclusion/Significance Our results provide the first evidence that the G allele of CRYAB C-802G is correlated with oral cancer risk and this polymorphism may be a useful marker for oral cancer recurrence and survival prediction for clinical reference.

Significant Association of Caveolin-1 Genotypes with Bladder Cancer Susceptibility in Taiwan

Many articles have reported the caveolin-1 gene to be down-regulated thus suggesting that it might be a candidate tumor suppressor gene in many tumors. However, its involvement in bladder cancer is not clear and may be depending on pathological grade. In this case-control study, the association of Cav-1 polymorphisms with bladder cancer risk in a central Taiwanese population was investigated. Three hundred and seventy-five patients with bladder cancer and the same number of age- and gender-matched healthy controls were genotyped. There were significant differences between bladder cancer and control groups in the distributions of their genotypes (P = 1.0 x 10(-12) and 0.299) and allelic frequencies (P = 1.4 x 10(-14) and 6.2 x 10(-3)) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) polymorphisms, respectively. As for haplotype analysis, subjects who had GG/AT or GG/AA at Cav-1 G14713A/T29107A showed a decreased risk of bladder cancer compared to subjects with GG/TT, while those of any other combinations were of increased risk. There were joint effects of Cav-1 G14713A and T29107A genotypes with smoking status on individual bladder cancer susceptibility. This is the first report providing evidence that Cav-1 was involved in bladder cancer in that the A allele of the Cav-1 G14713A is risky, the A allele of the Cav-1 T29107A is protective, and AA/TT on these two polymorphisms may be the most risky haplotype for the development of bladder cancer and may be novel useful genomic markers for early detection of bladder cancer.

Significant Association of XPD Asp312Asn Polymorphism with Breast Cancer in Taiwanese Patients

The DNA repair gene XPD, an important caretaker of the overall genome stability, is thought to play a major role in the development of human malignancy. Polymorphic variants of XPD, at Asp312Asn (rs1799793), Lys751Gln (rs13181), and promoter C-114G (rs3810366), were chosen to be studied of their association with breast cancer susceptibility in a central Taiwanese population. In this hospital-based case-control study, the associations of XPD Asp312Asn, Lys751Gln and promoter C-114G polymorphisms with breast cancer risk were investigated. In total, 1232 patients with breast cancer and 1433 healthy controls recruited from the China Medical Hospital in Central Taiwan were genotyped. We found a significant difference in the frequency of the XPD Asp312Asn genotype, but not the XPD Lys751Gln or promoter C-114G genotypes, between the breast cancer and control groups. Those who had G/A or A/A at XPD Asp312Asn showed a 1.78-fold (95% confidence interval = 1.53-2.08) increased risk of breast cancer compared to those with G/G. As for XPD Lys751Gln or promoter C-114G, there was no difference in distribution between the breast cancer and control groups. Our findings suggest that the heterozygous and homozygous A allele of the XPD Asp312Asn may be associated with the development of breast cancer and may be a useful marker for primary prevention and anticancer intervention.