Yu-Ching Chou

Anthropometric measures, plasma adiponectin, and breast cancer risk

Adiponectin is a peptide hormone secreted exclusively by adipocytes, and obesity is an established risk factor for breast cancer. We have, thus, evaluated the associations of anthropometric measures of adiposity and adiponectin with the development of breast cancer in a case-control study. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 244 incident cases with breast cancer, including 141 premenopausal and 103 postmenopausal cases, and 244 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2005. Plasma levels of adiponectin were measured by RIA. The relationship between anthropometric measures of adiposity and breast cancer risk was modified by menopausal status, with a significant increase in risk observed in postmenopausal but not premenopausal women. Moreover, a fairly robust inverse association of adiponectin with the risk was observed only in postmenopausal women (adjusted odds ratio (OR), 0.55; 95% confidence interval (CI), 0.23-0.97), but not in premenopausal women. Additionally, the plasma adiponectin levels tended to be inversely associated with estrogen receptor (ER)-positive (adjusted OR, 0.53; 95% CI, 0.27-0.98) but not ER-negative breast tumors. Furthermore, the associations of adiponectin with breast cancer risk overall and by menopausal and ER status remained after adjustment for obesity indices. These results suggest that adiponectin may have an independent role in breast carcinogenesis, particularly in the postmenopausal and ER-positive breast cancer risk.

Genetic variants of myeloperoxidase and catechol-O-methyltransferase and breast cancer risk.

This nested case–control study evaluated the role of polymorphisms in the myeloperoxidase (MPO) and catechol-O-methyltransferase (COMT) genes that modulate oxidative stress in breast cancer risk in a Chinese population. Our results demonstrate that the MPO A/A genotype was associated with a reduced risk of breast cancer (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.11–3.76), whereas there was no overall association of COMT genotype with breast cancer. Of note, an elevated breast cancer risk associated with the increasing numbers of high-risk genotypes of MPO and COMT genes was observed in women with a longer duration between menarche and first full-term pregnancy.

Vitamin D Decreases Risk of Breast Cancer in Premenopausal Women of Normal Weight in Subtropical Taiwan

Background Evidence for an association between vitamin D status and breast cancer is now more convincing, but is uncertain in subtropical areas like Taiwan. This hospital-based case-control study examined the relationship of breast cancer with vitamin D intake and sunlight exposure. Methods A total of 200 incident breast cancer cases in a Taipei hospital were matched with 200 controls by date of interview and menopausal status. Information on risk factors for breast cancer was collected in face-to-face interviews and assessed with reference to vitamin D intake (foods and nutrients) and sunlight exposure. Vitamin D intake was divided into quartiles, and threshold effect was evaluated by comparing Q2–Q4 with Q1. Results After controlling for age, education, parity, hormone replacement therapy, body mass index (BMI), energy intake, menopausal status, and daily sunlight exposure, the risk of breast cancer in participants with a dietary vitamin D intake greater than 5 µg per day was significantly lower (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.24–0.97) than that of participants with an intake less than 2 µg per day. In analysis stratified by menopausal status and BMI, both dietary vitamin D and total vitamin D intakes were associated with a protective effect among premenopausal women. There was a significant linear trend for breast cancer risk and dietary vitamin D intake in premenopausal women (P = 0.02). In participants with a BMI lower than 24 kg/m2 (ie, normal weight), dietary vitamin D intake was inversely related to breast cancer risk (P for trend = 0.002), and a threshold effect was apparent (Q2–Q4 vs Q1: OR, 0.46; 95% CI, 0.23–0.90). Conclusions Vitamin D had a protective effect against breast cancer in premenopausal women of normal weight in subtropical Taiwan, especially an intake greater than 5 µg per day.

Gene Expression Profiling of Colorectal Tumors and Normal Mucosa by Microarrays Meta-Analysis Using Prediction Analysis of Microarray, Artificial Neural Network, Classification, and Regression Trees

Background. Microarray technology shows great potential but previous studies were limited by small number of samples in the colorectal cancer (CRC) research. The aims of this study are to investigate gene expression profile of CRCs by pooling cDNA microarrays using PAM, ANN, and decision trees (CART and C5.0). Methods. Pooled 16 datasets contained 88 normal mucosal tissues and 1186 CRCs. PAM was performed to identify significant expressed genes in CRCs and models of PAM, ANN, CART, and C5.0 were constructed for screening candidate genes via ranking gene order of significances. Results. The first screening identified 55 genes. The test accuracy of each model was over 0.97 averagely. Less than eight genes achieve excellent classification accuracy. Combining the results of four models, we found the top eight differential genes in CRCs; suppressor genes, CA7, SPIB, GUCA2B, AQP8, IL6R and CWH43; oncogenes, SPP1 and TCN1. Genes of higher significances showed lower variation in rank ordering by different methods. Conclusion. We adopted a two-tier genetic screen, which not only reduced the number of candidate genes but also yielded good accuracy (nearly 100%). This method can be applied to future studies. Among the top eight genes, CA7, TCN1, and CWH43 have not been reported to be related to CRC.

Relationships between critical period of estrogen exposure and circulating levels of insulin-like growth factor-I (IGF-I) in breast cancer: evidence from a case-control study.

Epidemiological observations suggest that insulin‐like growth factor‐I (IGF‐I), a potent mitogenic and anti‐apoptotic peptide, plays a role in the etiology of breast cancer. Estrogen, which is crucial in breast carcinogenesis, both regulates and is influenced by IGF‐I family. A case‐control study was conducted to assess the role of IGF‐I as a biomarker for breast cancer and to evaluate the potential joint effect of circulating IGF‐I and critical period of estrogen exposure, as estimated by the interval between age at menarche and age at first full‐term pregnancy on the risk of breast cancer. Questionnaire information and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri‐Service General Hospital, Taipei between 2004 and 2006. Plasma levels of IGF‐I and IGFBP‐3 were measured by immunoradiometric assay. Conditional logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our case‐control data indicate that breast cancer risk related to IGF‐I differs according to menopausal status. High circulating levels of IGF‐I increased risk of pre‐ but not postmenopausal breast cancer (top vs. bottom tertile, adjusted OR, 1.86; 95% CI, 1.01–3.44). Furthermore, elevated IGF‐I concentrations in conjunction with prolonged interval of critical period of estrogen exposure were associated with significantly increased risk of breast cancer, particularly among estrogen‐positive cases (adjusted OR, 2.42, 95% CI, 1.33–4.38). These results suggest that the joint effect of IGF‐I and estrogens may provide novel methods of breast cancer risk reduction among women.

Androgen receptor gene CAG repeats, estrogen exposure status, and breast cancer susceptibility

The length of a polymorphic CAG repeat in exon 1 of the androgen receptor (AR) is inversely correlated with AR transactivation activity. As heightened androgenic stimulation may oppose breast cell proliferation, which is mediated by AR, we examined whether AR-CAG repeat lengths are related to breast cancer susceptibility. A nested case–control study of 88 newly diagnosed cases of breast cancer between 1992 and 2000 and 334 matched controls was carried out in Taiwanese women. Risk factors were obtained through a standardized questionnaire interview and blood samples were collected and used to determine the number of AR-CAG repeats. Women with one or more long AR (CAG)n repeat alleles (>22 repeats) were not at significantly increased risk of breast cancer [odds ratio (OR), 1.52; 95% confidence interval (CI), 0.80–2.90]. Of particular interest was a significantly increased risk associated with the long-allele AR genotype that was present mostly among women with a short duration (<10 years) of early estrogen exposure, as indicated by the interval between age at menarche and age at first full-term pregnancy, as compared with short AR allele genotypes (OR, 2.70; 95% CI, 1.00–7.31), although no such significant association in women with a long duration of early estrogen exposure (OR, 0.70; 95% CI, 0.25–1.59) was detected. These data suggest that longer AR (CAG)n repeat alleles may confer an increased risk of breast cancer among particular subsets of individuals, although these findings need replication in other populations.

Association between Hyperuricemia and Metabolic Syndrome: An Epidemiological Study of a Labor Force Population in Taiwan

The increasing prevalence of metabolic syndrome (MetS) has become an important issue worldwide. Metabolic comorbidities of hypertension, obesity, and hyperlipidemia are shown as important risk factors for incident gout. The purpose of this study was to investigate the relationship between hyperuricemia and MetS. This is a cross-sectional study. The effective sample included 21,544 individuals who received worker health examinations at a local teaching hospital in Changhua County from 2008~2012. We used multiple logistic regression analysis to investigate the influences of hyperuricemia on MetS. The results showed that individuals with MetS had significantly higher blood pressure, fasting plasma glucose, triglycerides, waist circumference, and high-density lipoprotein cholesterol than those without MetS (P < 0.001). Multiple logistic regression analysis revealed hyperuricemia to be an important factor of MetS. The risk of developing MetS is higher with high levels of serum uric acid (SUA) and the odds ratio (OR) of having MetS is 4.98 times higher for Tertile 3 than for Tertile 1 (95% CI = 4.16–5.97) and 4 times higher for Quartile 4 than for Quartile 1 (95% CI = 3.59–4.46). In conclusion, males are more likely to develop MetS than females, and the risk of having MetS increases with age and SUA concentration.

Gene expression profile of peripheral blood in colorectal cancer.

AIM Optimal molecular markers for detecting colorectal cancer (CRC) in a blood-based assay were evaluated. METHODS A matched (by variables of age and sex) case-control design (111 CRC and 227 non-cancer samples) was applied. Total RNAs isolated from the 338 blood samples were reverse-transcribed, and the relative transcript levels of candidate genes were analyzed. The training set was made of 162 random samples of the total 338 samples. A logistic regression analysis was performed, and odds ratios for each gene were determined between CRC and non-cancer. The samples (n = 176) in the testing set were used to validate the logistic model, and an inferred performance (generality) was verified. By pooling 12 public microarray datasets(GSE 4107, 4183, 8671, 9348, 10961, 13067, 13294, 13471, 14333, 15960, 17538, and 18105), which included 519 cases of adenocarcinoma and 88 controls of normal mucosa, we were able to verify the selected genes from logistic models and estimate their external generality. RESULTS The logistic regression analysis resulted in the selection of five significant genes (P < 0.05; MDM2, DUSP6, CPEB4, MMD, and EIF2S3), with odds ratios of 2.978, 6.029, 3.776, 0.538 and 0.138, respectively. The five-gene model performed stably for the discrimination of CRC cases from controls in the training set, with accuracies ranging from 73.9% to 87.0%, a sensitivity of 95% and a specificity of 95%. In addition, a good performance in the test set was obtained using the discrimination model, providing 83.5% accuracy, 66.0% sensitivity, 92.0% specificity, a positive predictive value of 89.2% and a negative predictive value of 73.0%. Multivariate logistic regressions analyzed 12 pooled public microarray data sets as an external validation. Models that provided similar expected and observed event rates in subgroups were termed well calibrated. A model in which MDM2, DUSP6, CPEB4, MMD, and EIF2S3 were selected showed the result in logistic regression analysis (H-L P = 0.460, R2= 0.853, AUC = 0.978, accuracy = 0.949, specificity = 0.818 and sensitivity = 0.971). CONCLUSION A novel gene expression profile was associated with CRC and can potentially be applied to blood-based detection assays.

The prevalence of metabolic syndrome and factors associated with quality of dialysis among hemodialysis patients in Southern Taiwan.

Objectives: The purpose of this study was to evaluate the prevalence of metabolic syndrome (MetS) among hemodialysis patients and factors associated with quality of dialysis. Methods: Data were collected from 377 long-term hemodialysis patients who received hemodialysis treatment from clinics in Tainan and Kaohsiung between November 2009 and February 2010. MetS was defined using criteria set by the adult treatment panel III (ATP-III). But, the cutpoint of waist circumference has been modified to adjust for Asian populations. The measurement of Kt/V was used as an indicator of the quality of dialysis. A below 1.4 Kt/V was considered poor dialysis quality. Results: Results showed that the prevalence of MetS among the chronic hemodialysis patients in this sample was 61.0%. Logistic regression results identified that the quality of dialysis in females was better than that in males (odds ratio (OR)=7.98, 95% confidence interval (CI): 2.52-25.31). Better quality dialysis was associated with older age, longer treatment time, and increased blood flow rate (OR=1.49, 13.63, and 1.35, respectively). However, for every one kilogram increase in weight, the quality of dialysis decreased by 13 percents (OR=0.87, 95% CI: 0.83-0.92). Conclusions: MetS is common among hemodialysis patients. The prevalence of hypertension, hyperlipidemia, and hyperglycaemia were significantly higher among hemodialysis patients. Quality of dialysis related to gender, age, weight, and the dialysis prescription (treatment time and blood flow rate).

Joint effect of peroxisome proliferator-activated receptor γ genetic polymorphisms and estrogen-related risk factors on breast cancer risk: results from a case–control study in Taiwan

Peroxisome proliferator-activated receptor γ (PPARγ) has been linked with possible antineoplastic effects in colorectal carcinogenesis. However, data for the possible link between PPARγ and breast cancer risk are sparse. We assessed the association of three polymorphisms in PPARγ (rs10865710 [C-681T], rs1805192 [Pro12Ala], and rs3856806 [C1431T]) with the risk of breast cancer in an ethnic Chinese female population in Taiwan. In addition, interactions with estrogen exposures were also explored. Genotypes for the PPARγ polymorphisms were determined on 291 incident breast cancer cases and 589 matched controls by fluorogenic 5′-nuclease assay. The at-risk haplotypes were defined according to the three polymorphisms in the following order: C-681T, Pro12Ala, and C1431T, which include CCT, GGT, and GGC. In addition, a critical period of estrogen exposure was estimated by the interval between age at menarche and age at first full-term pregnancy. Overall, there was no evidence of a significant impact of individual polymorphisms of PPARγ on breast cancer risk. However, the haplotype analysis revealed that women harboring at-risk haplotypes showed a significant 67% increase in breast cancer risk [adjusted odds ratio (OR) 1.67; 95% confidence interval (CI) 1.11–2.52]. Furthermore, there was a significant joint effect of estrogen exposure-related factors and at-risk haplotypes of PPARγ on breast cancer risk (adjusted OR 4.04; 95% CI 1.89–8.65), particularly in premenopausal women. The present study implicates a role for PPARγ in breast cancer risk. Mechanistic studies to fully elucidate the mechanisms underlying PPARγ’s effects should be pursued in future investigations.