Design and simulation of light field patterns for angular color variation reduction in micro-LED and mini-LED RGB arrays.

We propose a methodology to mitigate angular color variation in full-color micron-scale LED arrays. By simulating light field distribution for red (AlGaAs) and green/blue (GaN) light across various RGB micro-LED sizes, we can select matching light field patterns for RGB chips, reducing angular color variation from 0.0201 to 0.0030. Applying this method to full-color mini-LED assemblies achieves a reduction from 0.0128 to 0.0032 by matching light field patterns with varying substrate thicknesses. This straightforward approach aligns with current mass transfer processes, offering practical implementation.

Augmented reality system based on the integration of polarization-independent metalens and micro-LEDs.

Augmented reality (AR), a technology that superimposes virtual information onto a user's direct view of real-world scenes, is considered one of the next-generation display technologies and has been attracting considerable attention. Here, we propose a flat optic AR system that synergistically integrates a polarization-independent metalens with micro light-emitting diodes (LEDs). A key component is a meticulously designed metalens with a numerical aperture of 0.25, providing a simulated focusing efficiency of approximately 76.5% at a wavelength of 532 nm. Furthermore, the laser measurement system substantiates that the fabricated metalens achieves a focusing efficiency of 70.8%. By exploiting the reversibility of light characteristics, the metalens transforms the divergent light from green micro-LEDs into a collimated beam that passes through the pupil and images on the retina. Monochromatic pixels with a size of 5×5 µm2 and a pitch of 10 µm can be distinctly resolved with a power efficiency of 50%. This work illustrates the feasibility of integrating the metalens with microdisplays, realizing a high-efficiency AR device without the need for additional optical components and showcasing great potential for the development of near-eye display applications.

How should anti-hypertensive medications be adjusted before screening for primary aldosteronism?

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding ß-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.

Therapeutic inhibition of ATR in differentiated thyroid cancer.

Ataxia telangiectasia and Rad3-related protein (ATR) is a critical component of the DNA damage response and a potential target in the treatment of cancers. An ATR inhibitor, BAY 1895344, was evaluated for its use in differentiated thyroid cancer (DTC) therapy. BAY 1895344 inhibited cell viability in four DTC cell lines (TPC1, K1, FTC-133, and FTC-238) in a dose-dependent manner. BAY 1895344 treatment arrested DTC cells in the G2/M phase, increased caspase-3 activity, and caused apoptosis. BAY 1895344 in combination with either sorafenib or lenvatinib showed mainly synergistic effects in four DTC cell lines. The combination of BAY 1895344 with dabrafenib plus trametinib revealed synergistic effects in K1 cells that harbor BRAFV600E. BAY 1895344 monotherapy retarded the growth of K1 and FTC-133 tumors in xenograft models. The combinations of BAY 1895344 plus lenvatinib and BAY 1895344 with dabrafenib plus trametinib were more effective than any single therapy in a K1 xenograft model. No appreciable toxicity appeared in animals treated with either a single therapy or a combination treatment. Our findings provide the rationale for the development of clinical trials of BAY 1895344 in the treatment of DTC.

Current Confinement Effect on the Performance of Blue Light Micro-LEDs with 10 µm Dimension.

The current confinement effect on the micro-LED (µLED) with a 10 µm dimension was simulated using SpeCLED software. In this study, three p-contact sizes were considered: 2 µm × 2 µm, 5 µm × 5 µm, and 8 µm × 8 µm dimensions for µLEDs with a 10 µm dimension. According to the simulation data, the highest external quantum efficiency (EQE) of 13.24% was obtained with a 5 µm × 5 µm contact size. The simulation data also showed that the µLEDs with narrow contact sizes experienced higher operating temperatures due to the current crowding effect. The experimental data revealed a red-shift effect in narrow contact sizes, indicating higher heat generation in those devices. As the contact sizes increased from 2 to 8 µm, the turn-on voltage decreased due to lower equivalent resistance. Additionally, the leakage current increased from 44 pA to 1.6 nA at a reverse voltage of -5 V. The study found that the best performance was achieved with a contact ratio of 0.5, which resulted in the highest EQE at 9.95%. This superior performance can be attributed to the better current confinement of the µLED compared to the µLED with a contact ratio of 0.8, resulting in lower leakage current and improved current spreading when compared to the µLED with a contact ratio of 0.2.

The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes to Hepatocellular Carcinoma Susceptibility.

BACKGROUND/AIM: Metalloproteinase-7 (MMP-7) has been previously found to be up-regulated in hepatocellular carcinoma (HCC) specimens and cells, favoring epithelial-mesenchymal transition. However, the contribution of MMP-7 genotypes to HCC has not been revealed to date. The study aimed to evaluate the contribution of MMP-7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes on the risk of HCC in Taiwan, where HCC incidence is extremely high compared to worldwide data. MATERIALS AND METHODS: In this case-control study, MMP-7 genotypes and their association with cigarette smoking and alcohol drinking habits were determined in 298 HCC patients and 889 healthy subjects by a typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: Ever smokers and alcohol drinkers were represented with higher percentages in the case group compared to the control group. MMP-7 rs11568818 genotypes were not found differentially distributed in case and control groups (p for trend=0.5246). People of the analyzed cohort of the present study were all of CC genotypes at their rs11568819 polymorphic sites, without any CT or TT genotypes. As for gene-lifestyle interactions, people with variant genotypes at MMP-7 rs11568818 had the same odds for HCC development compared to the wild-type AA genotype, no matter whether the subjects belonged to the smoker, non-smoker alcohol drinker, or non-drinker groups. CONCLUSION: MMP-7 variant genotypes did not present any significance towards being a marker for HCC risk in Taiwanese.

Outcomes of Patients With Metastatic Differentiated Thyroid Cancer After Excellent Response to Treatment.

Background: To evaluate the outcomes in differentiated thyroid cancer (DTC) patients who achieved excellent response to initial treatment and developed distant metastasis during follow-up. Methods: Thyroid cancer patients registered in Chang Gung Memorial Hospital thyroid cancer database between January 1979 and December 2019 were assessed. Results: Among 1053 DTC patients with excellent response to initial therapy, 14 (1.3%) patients developed metastatic disease during follow-up, including 6 males and 8 females with median age of 50.2 years [interquartile range (IQR), 39.9-53.7]. Nine (64.3%) patients had papillary cancer, four (28.6%) had follicular cancer, and one (7.1%) had Hürthle cell cancer. Most patients (92.9%) had stage I disease at diagnosis. The sites of metastasis were lung (71.4%), bone (7.1%), mediastinum (7.1%) and multiple sites (14.3%). With a median follow-up of 18.3 years (IQR, 14.8-23.8), 2 patients had disease-specific mortality. The 5- and 10-year disease-specific survival after the diagnosis of distant metastasis was 92% and 74%, respectively. Multiple sites of metastasis was associated with increased risk of mortality (P = 0.022). Conclusions: A small proportion of DTC patients with an excellence response to initial therapy developed distant metastasis during follow-up. Multiple organ distant metastases conferred a worse disease-specific survival.

Contribution of 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase Genotypes to Colorectal Cancer in Taiwan.

BACKGROUND/AIM: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) is responsible for folate metabolism, and we aimed to investigate its genetic role in colorectal cancer (CRC) among Taiwanese. MATERIALS AND METHODS: A total of 362 cases and 362 controls were recruited and their MTRR rs1801394 (A66G) and rs1532268 (C524T) genotypes were examined. The behavioral factors and clinicalpathological factors were also analyzed. RESULTS: MTRR rs1801394 genotypes were associated with CRC risk (p for trend=0.0087). In detail, G/G genotype was associated with lower risk (p=0.0049, OR=0.39, 95%CI=0.20-0.76). As for allelic frequency analysis, G allele was also associated with decreased CRC risk (p=0.0026, OR=0.68, 95%CI=0.53-0.88). There was no significant association as for MTRR rs1532268. Among non-smokers and non-alcohol drinkers, those with G/G genotype were at 0.38- and 0.46-fold odds of having CRC. There were no significant protective effects among smokers or alcohol drinkers. CONCLUSION: MTRR rs1801394 GG genotype can be a protective marker for CRC risk in Taiwan.

Risk Factors and Prognosis for Metastatic Follicular Thyroid Cancer.

Background: Follicular thyroid cancer (FTC) is the second most common malignancy of thyroid. About 7%-23% of patients with FTC have distant metastasis. The aim of this study was to investigate the risk factors associated with distant metastasis and the impact of distant metastasis on survival in FTC patients. Methods: Patients with FTC were analyzed using a prospectively maintained dataset of thyroid cancer registered at a tertiary hospital in Taiwan between December 1976 and May 2020. Results: A total of 190 patients with a mean follow-up of 7.7 years were included in this study, including 29 with distant metastasis at diagnosis, 14 who developed metastasis during follow-up, and 147 without metastasis. Multivariate analysis adjusted for age, gender, tumor stage, and extrathyroidal invasion revealed old age (≥ 55 years) (adjusted odds ratio, 27.6; 95% confidence interval [CI], 8.75-86.8; P < 0.001) and extrathyroidal invasion (odds ratio, 24.1; 95% CI, 3.50-166.5; P = 0.001) were significantly associated with an increased risk of distant metastasis. Metastasis was correlated with higher cancer-specific mortality (adjusted hazard ratio, 35.5; 95% CI, 6.1-206.1; P < 0.001). In addition, patients with metastatic FTC diagnosed on initial presentation had the lowest 10-year cancer-specific survival rate (26.0%), followed by those who developed metastatic disease after initial treatment (76.6%), while patients without metastasis were all alive (100%) (P ≤ 0.002 for all comparisons). Conclusions: Age and extrathyroidal invasion are significant risk factors for distant metastasis of FTC. Patients with metastatic FTC, especially when diagnosed on initial presentation, have dismal survival outcomes.

Survival and Death Causes in Thyroid Cancer in Taiwan: A Nationwide Case-Control Cohort Study.

The incidence of thyroid cancer has increased substantially worldwide. However, the overall mortality risk and actual causes of death in thyroid cancer patients have not been extensively evaluated. In this study, patients with thyroid cancer diagnosed between 2001 and 2017 were analyzed from Taiwan's National Health Insurance Research Database. We compared these patients with control subjects matched for age, gender, history of cardiovascular disease (CVD), hyperlipidemia, diabetes mellitus, hypertension, and occupation to assess the risk of overall mortality and cause-specific mortality. Finally, our cohort comprised 30,778 patients with thyroid cancer. Three hundred and ninety-eight deaths (1.29%) occurred during a median follow-up of 60.0 months (range: 30.3 to 117.6 months). The primary cause of death was thyroid cancer mortality (31.2%), followed by other malignancy-related mortality (29.9%) and CVD mortality (12.3%). The overall mortality risk was similar between the thyroid cancer and control groups (unadjusted hazard ratio (HR): 0.98; 95% confidence interval (CI): 0.88-1.10); the adjusted HR was 1.07 (95% CI: 0.95-1.20) after multivariate adjustment for age, gender, history of CVD, hyperlipidemia, diabetes mellitus, hypertension, and occupation. The risk of other malignancy-related mortality was comparable between two groups. CVD mortality risk was lower in the thyroid cancer group, with an unadjusted HR of 0.51 (95% CI: 0.38-0.69) and adjusted HR of 0.56 (95% CI: 0.42-0.76). In conclusion, patients with thyroid cancer had excellent overall survival. Thyroid cancer-specific mortality was the leading cause of death, highlighting the importance of thyroid cancer management. Thyroid cancer patients had lower CVD mortality risk than the general population.

Efficacy and Biomarker Analysis of Adavosertib in Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) patients are usually known for their excellent prognoses. However, some patients with DTC develop refractory disease and require novel therapies with different therapeutic mechanisms. Targeting Wee1 with adavosertib has emerged as a novel strategy for cancer therapy. We determined the effects of adavosertib in four DTC cell lines. Adavosertib induces cell growth inhibition in a dose-dependent fashion. Cell cycle analyses revealed that cells were accumulated in the G2/M phase and apoptosis was induced by adavosertib in the four DTC tumor cell lines. The sensitivity of adavosertib correlated with baseline Wee1 expression. In vivo studies showed that adavosertib significantly inhibited the xenograft growth of papillary and follicular thyroid cancer tumor models. Adavosertib therapy, combined with dabrafenib and trametinib, had strong synergism in vitro, and revealed robust tumor growth suppression in vivo in a xenograft model of papillary thyroid cancer harboring mutant BRAFV600E, without appreciable toxicity. Furthermore, combination of adavosertib with lenvatinib was more effective than either agent alone in a xenograft model of follicular thyroid cancer. These results show that adavosertib has the potential in treating DTC.

Contribution of Matrix Metalloproteinase-1 Genotypes to Colorectal Cancer in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinase-1 is responsible for extracellular matrix regulation, and its genetic role in colorectal cancer (CRC) is unclear. The aim of the study was to investigate the contribution of Matrix metalloproteinase-1 genotypes to CRC risk in Taiwan. MATERIALS AND METHODS: A total of 362 cases and 362 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined. The environmental factors and clinical-pathological records were also analyzed. RESULTS: The genotypic frequency of MMP-1 rs1799750 were different between the CRC and control groups (p for trend=0.0083). 1G/2G and 1G/1G were associated with lower risk (p=0.0438 and 0.0030, adjusted OR=0.73 and 0.54, 95%CI=0.54-0.90 and 0.37-0.83). Among non-smokers, those with 1G/2G and 1G/1G genotypes were at 0.70- and 0.48-fold odds of having CRC. Among non-alcohol drinkers, people with 1G/2G and 1G/1G genotypes were at 0.71- and 0.54-fold odds. The 1G/1G genotype were statistically lower among CRC patients with lymph node metastasis (7.2%) than those without (19.0%). CONCLUSION: The genotypes at MMP-1 rs1799705 play a role in determining susceptibility to CRC risk in Taiwan.

Efficacy of adavosertib therapy against anaplastic thyroid cancer.

Wee1 is a kinase that regulates the G2/M progression by the inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease. The therapeutic effects of adavosertib, a Wee1 inhibitor for anaplastic thyroid cancer was evaluated in this study. Adavosertib inhibited cell growth in three anaplastic thyroid cancer cell lines in a dose-dependent manner. Cell cycle analysis revealed cells were accumulated in the G2/M phase. Adavosertib induced caspase-3 activity and led to apoptosis. Adavosertib monotherapy showed significant retardation of the growth of two anaplastic thyroid cancer tumor models. The combination of adavosertib with dabrafenib and trametinib revealed strong synergism in vitro and demonstrated robust suppression of tumor growth in vivo in anaplastic thyroid cancer xenograft models with BRAFV600E mutation. The combination of adavosertib with either sorafenib or lenvatinib also demonstrated synergism in vitro and had strong inhibition of tumor growth in vivo in an anaplastic thyroid cancer xenograft model. No appreciable toxicity appeared in mice treated with either a single agent or combination treatment. Our findings suggest adavosertib holds the promise for the treatment of patients with anaplastic thyroid cancer.

Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease.

Albuminuria is a measurement and determinant factor for diabetic kidney disease (DKD). Angiotensin receptor blocker (ARB) is recommended for albuminuria in DKD with variable response. To find surrogate markers to predict the therapeutic effect of ARB, we carried out a prospective study to correlate plasma metabolites and the progression of renal function/albuminuria in DKD patients. A total of 56 type 2 diabetic patients with various stages of chronic kidney disease and albuminuria were recruited. ARB was prescribed once albuminuria was established. Urinary albumin-to-creatinine ratio (UACR) was determined before and six months after ARB treatment, with a ≥30% reduction of UACR considered an ARB responder. Plasma levels of 145 metabolites were measured before ARB treatment; only those associated with albuminuria were selected and compared between ARB responders and non-responders. Both lower tryptophan (Trp ≤ 46.75 µmol/L) levels and a higher kynurenine/tryptophan ratio (KTR ≥ 68.5 × 10-3) were significantly associated with macroalbuminuria (MAU), but only KTR (≥54.7 × 10-3) predicts ARB responsiveness (sensitivity 90.0%, specificity 50%) in MAU. Together, these data suggest that the kynurenine/tryptophan ratio predicts angiotensin receptor blocker responsiveness in patients with diabetic kidney disease.

Association of Matrix Metalloproteinase-9 rs3918242 Promoter Genotypes With Colorectal Cancer Risk.

BACKGROUND/AIM: Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk. MATERIALS AND METHODS: A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location. CONCLUSION: MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.

Contribution of Caspase-8 Genotypes to Colorectal Cancer Risk in Taiwan.

BACKGROUND/AIM: The aim of this study was to examine the role of caspase-8 rs3834129 polymorphism on colorectal cancer (CRC) risk in Taiwanese CRC patients and healthy controls. MATERIALS AND METHODS: The caspase-8 rs3834129 (-652 6N insertion/deletion) polymorphic genotypes were analyzed in 362 patients with CRC and the same number of age- and gender-matched healthy subjects. The interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS: The percentage of variants ID and DD for caspase-8 rs3834129 genotype were 37.6 and 5.8% in CRC group and 39.0 and 6.6% in the control group, respectively (p for trend=0.7987). The allelic frequency distribution analysis showed that caspase-8 rs3834129 D allele conferred a non-significant lower susceptibility for CRC compared with I allele (OR=0.92, 95%CI=0.74-1.20, p=0.5063). There was no obvious link between caspase-8 rs3834129 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No statistically significant correlation was observed between caspase-8 rs3834129 genotypic distribution and age, gender, tumor size, location or metastasis status. CONCLUSION: Overall, caspase-8 rs3834129 genotypes may not serve as predictors for CRC risk or prognosis.

Diagnostic value of adrenal iodine-131 6-beta-iodomethyl-19-norcholesterol scintigraphy for primary aldosteronism: a retrospective study at a medical center in North Taiwan.

BACKGROUND: Primary aldosteronism (PA) is a common cause of secondary hypertension. Among the many leading causes of PA, the two most frequent are, bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenomas (APA). Since a solitary APA may be cured surgically, but BAH needs lifelong pharmacologic therapy, confirmation is mandatory before surgery. We herein sought to determine the diagnostic value of iodine-131 6-beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy to distinguish BAH from APA. PATIENTS AND METHODS: Patients clinically suspected of PA from March 2000 to October 2016 were retrospectively analyzed. A total of 145 patients, including 74 postunilateral adrenalectomy and seven postradiofrequency ablation for adrenal mass, were reviewed. All patients received NP-59 adrenal scintigraphy prior to surgery. The accuracy of the NP-59 adrenal scintigraphy was confirmed by the pathologic findings and postoperative outcomes. RESULTS: Among 81 patients receiving interventional procedures for adrenal mass, adenoma was eventually diagnosed in 72 patients according to their pathologic results, with 60 unilaterally and seven bilaterally localized lesions by NP-59 scintigraphy; nevertheless, there were five negative findings initially. The sensitivity, specificity, and positive predictive value of NP-59 scintigraphy for APA detection were therefore 83.3, 44.4, and 92.3%, respectively. Moreover, single-photon emission computed tomography/computed tomography scan increased the sensitivity and specificity, but not the positive predictive value (85.0, 60.0, and 89.5%) of NP-59 scintigraphy in this study. CONCLUSION: NP-59 adrenal scintigraphy is a useful imaging test to detect APA. Lateralization by this modality prior to surgical intervention may reduce the need for such invasive procedures as adrenal venous sampling.

Contribution of Murine Double Minute 2 Genotypes to Colorectal Cancer Risk in Taiwan.

BACKGROUND/AIM: The genomic role of human mouse double minute 2 (MDM2) in colorectal cancer (CRC) is unclear, therefore, our study aimed to evaluate the contribution of MDM2 genotype to the risk of CRC in Taiwan. MATERIALS AND METHODS: In this case-control study, MDM2 SNP309 T to G (rs2279744) genotypes were determined and their association with CRC risk were investigated among 362 patients with CRC and 362 age- and gender-matched healthy controls in central Taiwan. In addition, the interaction of MDM2 SNP309 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS: The percentage of variant GG for the MDM2 SNP309 genotype was 30.9% in the CRC group and 24.0% in the control group, respectively (odds ratio (OR)=1.78, 95% confidence interval (CI)=1.25-2.86, p=0.0057). The allelic frequency distribution analysis showed that the variant G allele of MDM2 SNP309 conferred a significantly increased susceptibility to CRC compared with the wild-type T allele (OR=1.32, 95% CI=1.14-1.69, p=0.0062). As for the gene-lifestyle interaction, there was an obvious joint effect of MDM2 SNP309 GG genotype on the risk of CRC among ever-smokers and non-alcohol drinkers, but not non-smoker or alcohol drinker subgroups. No statistically significant correlation was observed between MDM2 SNP309 genotypic distributions and age, gender, tumor size, location or metastasis status. CONCLUSION: The genotypes of MDM2 SNP309 may allow forr early detection of and predictor for CRC risk, especially among smokers and non-alcohol drinkers, but not for prognosis. The combined effects of MDM2 SNP309 and other genes (such as matrix metalloproteinases) on CRC susceptibility and prognosis, should also be taken into consideration in the era of precision medicine.

The Contribution of MMP-7 Genotypes to Colorectal Cancer Susceptibility in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) play important roles in inflammation and carcinogenesis, but the genotypic role of MMP-7 has never been investigated in colorectal cancer (CRC) among the Taiwanese. Therefore, in this study we aimed to evaluate the contribution of MMP-7 genotypes to the risk of CRC in Taiwan. MATERIALS AND METHODS: In this case-control study, MMP-7 A-181G and C-153T promoter genotypes were determined and their association with CRC risk were investigated among 362 CRC patients and 362 age- and gender-matched healthy controls. In addition, the interaction of MMP-7 genotypes and personal behaviors were also examined. RESULTS: The percentages of variant AG and GG for MMP-7 A-181G genotypes were 10.5% and 1.7% in the CRC group and 11.9% and 2.2% in the control group, respectively (p for trend=0.7145). The allelic frequency distribution analysis showed that the variant G allele of MMP-7 A-181G conferred a slight but non-significant decreased CRC susceptibility to the wild-type C allele (odds ratio (OR)=0.86, 95% confidence interval (CI)=0.64-1.31, p=0.37). Taiwanese all harbour the CC genotype at MMP-7 C-153T. As for the gene-lifestyle interaction, there were no obvious joint effects of MMP-7 A-181G genotype on the risk of CRC among ever smoker, alcohol drinker, non-smoker or non-drinker subgroups. No statistically significant correlation was observed between MMP-7 A-181G genotypic distributions and age, gender, tumor size, location or metastasis status. CONCLUSION: The genotypes of MMP-7 A-181G may play an indirect role in determining personal susceptibility to CRC and prognosis. The further genotyping work on MMP-7 and other genes (such as other MMPs, oncogenes and tumor suppression genes) on CRC susceptibility and prognosis, should be taken into consideration spontaneously in the precision medicine era.

Contribution of Matrix Metalloproteinase-7 Genotypes to the Risk of Non-solid Tumor, Childhood Leukemia.

BACKGROUND/AIM: The matrix metalloproteinases (MMPs) are important in inflammation and carcinogenesis, and the genotypic role of MMP7 has never been examined in leukemia to date. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. MATERIALS AND METHODS: In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distribution of AA, AG and GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p for trend=0.0134), significantly differentially distributed between childhood ALL and control groups. The comparisons in allelic frequency distribution also support the findings that G appears to be the risky allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs) (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying wild-type AA genotype. But these differences were not found in girls. Analysis of genotype interaction with age of onset age showed those aged less than 3.5 years at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and 2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. CONCLUSION: Our results indicate that the MMP7 A-181G genotype interacts with age and gender and may serve as an early and predictive biomarker for childhood ALL.