Thitiya Sirisinha

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): Validation study of the Thai version

The objective of this study was to assess the psychometric properties of the Thai version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0. The questionnaire was completed by 310 cancer patients during their follow-up at 2 teaching hospital oncology clinics. About 70% of participants had advanced stage of cancer and 72% had been receiving chemotherapy. Cronbach’s α coefficients of the six scales were above 0.7, except for cognitive and social function scales. All test–retest reliability coefficients were high. Multitrait scaling analysis showed that all item-scale correlation coefficients met the standards of convergent and discriminant validity. Most scales and items could discriminate between subgroups of patients with different clinical status assessed with the Eastern Cooperative Oncology Group (ECOG) scale. The results suggested that the EORTC QLQ-C30 and the Functional Assessment of Cancer Therapy – General (FACT-G) measured different aspects of quality of life and should be independently used. Testing psychometric properties of the EORTC QLQ-C30 in heterogeneous diagnostic group yield similar results as found in homogeneous group. These results support that the EORTC QLQ-C30 (version 3.0) has proven to be a reliable and valid measure of the quality of life in Thai patients with various types of cancer.

Impact of CYP2D6 polymorphisms on tamoxifen responses of women with breast cancer: a microarray-based study in Thailand.

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Associations between genotypes-phenotypes and disease free survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years. The 3 common allelic frequencies were 43.8% (*10), 36.5 (*1) and 10.4% (*2) which are related to extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No association between CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statistically significant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95% CI, 1.48 -31.69; P = 0.005). Furthermore, we observed statistically significant shorter DFS of homozygous CYP2D6*10 when compared with heterozygous CYP2D6*10 and other genotypes (P=0.005). CYP2D6*10 was the most common genotype in our subjects. Post-menopause patients with homozygous CYP2D6*10 and IM have shorter DFS. To confirm this relationship, larger samples and comprehensively designed trials in Thailand are required.

CYP2D6 polymorphisms influence the efficacy of adjuvant tamoxifen in Thai breast cancer patients.

Aim: We evaluated single nucleotide polymorphisms (SNPs) of CYP2D6 to identify those that influence the efficiency of tamoxifen in adjuvant treatment of breast cancer through a matched case–control study. Methods: Peripheral blood DNA was collected from 20 patients with disease recurrence during adjuvant tamoxifen treatment and from 19 patients who had completed 5 years of tamoxifen therapy without recurrence of breast cancer. CYP2D6*4 (1846G > A; rs3892097), CYP2D6*10 (100C > T, rs1065852), and CYP2D6*5 (deletion) were genotyped. The correlation between disease-free survival (DFS) and genotype and clinical outcome were assessed using Kaplan–Meier analysis and a log-rank test. Results: We found the allelic frequency of CYP2D6*10 during this study. Patients with the CYP2D6*10 homozygous variant T/T genotype had a significantly shorter median of DFS than those with C/T (P = 0.036), but DFS was not significantly different from that of patients with the C/C genotype (P = 0.316). One patient who was a carrier both of CYP2D6 G/A (1846G > A) and T/T (100C > T) had DFS of 22.7 months. Conclusions: This study demonstrated that CYP2D6*10/*10 was significantly associated with shorter DFS in Thai breast cancer patients receiving tamoxifen. This was a pilot study investigating the correlation of CYP2D6 polymorphisms and their influence on clinical outcomes in Thai estrogen receptor-positive breast cancer patients.

Pharmacogenetic Study of 5-Fluorouracil-Related Severe Toxicity in Thai Cancer Patients: A Novel SNP Detection

Objective: The objective of this study is to determine the extent of (DPYD) Dihydropyrimidine Dehydrogenase Gene] polymorphisms of Thai cancer patients who received 5-FU based chemotherapy regimens. Methods: The study was conducted a pharmacogenetic analysis to determine the polymorphisms of DPYD gene in 116. Thai cancer patients. 76 patients developed severe (grade 3-4) toxicities after receiving the first or second cycle of 5-FU based chemotherapy. The other subject group consisted of 40 patients without severe toxicity. The DNA sequencing of every amplicon was done to identify 11 mutations as reported in Asian population. The actual change of absolute neutrophil count (ANC), hematocrit, platelet and percentage of neutrophil were compared. Results: We detected 13 SNPs of which 6 SNPs were found in exons; 967G>A, 1011A>T, 1236G>A, 1774C>T, 1896T>C and 1627A>G. The other 7 SNPs were found in intron but only IVS14+1G>A is the intron splice site. We found homozygous GG of 1627A>G in 4 patients who had severe toxicities. Statistically significant difference in actual ANC change and percentage of neutrophil change in homozygous GG [P = .011 and .009] were found. The median nadir ANC of homozygous GG is 399.6 cells/mm3. This SNP has cause the amino acid change from isoleucine to valine. Novel heterozygous SNPs (967G>A, 1774C>T) that cause the amino acid change were found in two patients with severe toxicities. Conclusions: 1627A>G, 967G>A, 1774C>T and IVS14+G>A might be the cause of (DPD) Dihydro Pyrimidine Dehydrogenase deficiency in Thai patients. The further study needs to establish the functional DPD protein in this population. Ten novel SNPs were discovered in our study.