Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015-4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022-2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250-2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.

Hepatocellular carcinoma (HCC) is a major malignancy of cancer-related mortality worldwide. Metastasis-associated in colon cancer-1 (MACC1) was suggested as a marker for vascular invasive HCC. This study investigated the MACC1 single-nucleotide polymorphisms (SNPs) to evaluate HCC susceptibility and clinicopathological characteristics. In this study, real-time polymerase chain reaction was applied to analyze five SNPs of MACC1 rs1990172, rs975263, rs3095007, rs4721888, and rs3735615 in 378 patients with HCC and 1199 cancer-free controls. The results showed that in 151 HCC patients among smokers who carried MACC1 rs1990172 "CA + AA" variants had a lower risk of developing a large tumor (odds ratio [OR] = 0.375, p = 0.026), more advanced clinical stage ([OR] = 0.390, p=0.032), and vascular invasion ([OR] = 0.198, p = 0.034). In 137 HCC patients among drinkers who carried MACC1 rs4721888 "GC + CC" variants had a higher risk to develop vascular invasion ([OR] = 3.780, p = 0.009). Further analyses revealed a statistical significance of aberrant AST/ALT ratio in HCC patients with MACC1 rs975263 "AG+GG" variants before adjustment of age and alcohol drinking. In conclusion, our results suggested that the MACC1 SNPs rs1990172, rs4721888, and rs975263 are involved in HCC progression and clinical characteristics. MACC1 polymorphisms may serve as a marker or a predictor to evaluate HCC progression and prognosis.

Long pentraxin 3 (PTX3) is produced by various cell types and is correlated with tumor progression in various tumor types. However, the clinical significance of PTX3 polymorphisms in oral cancer and their correlation with the risk of cancer are still unclear. In this study, we assessed the influence of PTX3 gene polymorphisms and environmental factors on susceptibility to oral tumorigenesis. We recruited 865 cases with oral cancer and 1,189 controls. Four single-nucleotide variations of the PTX3 gene (rs1840680, rs2305619, rs3816527, and rs2120243) were verified using a real-time polymerase chain reaction in control participants and cases with oral cancer. We found that rs3816527 in smokers was correlated with the development of late-stage cancer (odds ratio [OR], 2.328; 95% confidence interval [CI], 1.078-5.027) and increased lymph node metastasis (OR, 2.152; 95% CI, 1.047-4.422). Moreover, additional bioinformatics analysis results showed that the rs3816527 C allele variant to the A allele exhibited the strongest exonic splicing enhancer activity. In conclusion, our results suggested that PTX3 rs3816527 plays a role in oral cancer development.

CD26/dipeptidyl peptidase IV (DPP4) is a multifunctional cell-surface glycoprotein widely found in many cell types, and a soluble form is present in body fluids. There is longstanding evidence indicating a tumour-promoting or -suppressive role of DPP4 in different cancer types. However, studies focusing on the impacts of genetic variants of DPP4 on cancers are very rare. Herein, we conducted a case-control study to evaluate whether single-nucleotide polymorphisms (SNPs) of DPP4 were associated with the risk or clinicopathologic development of prostate cancer (PCa). We genotyped four loci of DPP4 SNPs, including rs7608798 (A/G), rs3788979 (C/T), rs2268889 (T/C) and rs6741949 (G/C), using a TaqMan allelic discrimination assay in 704 PCa patients and 704 healthy controls. Our results showed that PCa patients with the DPP4 rs7608798 AG+GG genotype or rs2268889 TC+CC genotype had a higher risk of developing an advanced clinical primary tumour (cT) stage (adjusted odds ratio (AOR): 1.680, 95% confidence interval (CI): 1.062-2.659, p = 0.025; AOR: 1.693, 95% CI: 1.092-2.624, p = 0.018). Additionally, in The Cancer Genome Atlas (TCGA) database, we observed that lower DPP4 expression levels were correlated with higher Gleason scores, advanced cT and pathological stages, tumour metastasis, and shorter progression-free survival rates in PCa patients. Furthermore, overexpression of DPP4 suppressed migration/invasion of metastatic PC3 PCa cells. Our findings suggest that DPP4 levels may affect the progression of PCa, and the DPP4 rs7608798 and rs2268889 SNPs are associated with the clinicopathologic development of PCa in a Taiwanese population.

Fibroblast growth factor receptor 4 (FGFR4) is involved in multiple physiological and pathological processes. Several genetic variants of FGFR4 have been shown to be associated with tumor progression in many cancers. However, its association, such as genetic variants and expression levels, with lung cancer is controversial. The present study examined the relationship between four single-nucleotide polymorphisms (SNPs; rs2011077 T/C, rs351855 G/A, rs7708357 G/A, and rs1966265 A/G) of FGFR4 and the risk of lung adenocarcinoma with the epidermal growth factor receptor (EGFR) mutation status in a Taiwanese cohort. The results demonstrated that FGFR4 rs2011077 (odds ratio (OR) = 0.348, 95% confidence interval (CI) = 0.136-0.891, p = 0.024), and rs351855 (OR = 0.296, 95% CI = 0.116-0.751, p = 0.008) showed an inverse association with distant metastasis in wild-type EGFR lung adenocarcinoma. Furthermore, a database analysis using The Cancer Genome Atlas revealed that the higher FGFR4 expression level was correlated with poor survival rates in wild-type EGFR lung adenocarcinoma. In conclusion, the data suggest that FGFR4 SNPs may help in identifying patient subgroups at low-risk for tumor metastasis, among carriers of lung adenocarcinoma bearing wild-type EGFR.

A disintegrin and metalloprotease (ADAM) family proteins are type-I transmembrane glycoproteins with multiple functions in cell adhesion, migration, proteolysis and signaling. ADAM10 is a member of the ADAM family reportedly involved in cancer progression and has been shown to be overexpressed in hepatocellular carcinoma (HCC) tissues and significantly associated with tumor progression and shortened survival. This study investigated ADAM10's single nucleotide polymorphisms (SNPs) and their association to HCC development and regulation. Real-time polymerase chain reaction was used to analyze five SNPs of ADAM10 in 333 patients with HCC and 1196 controls without cancer. The results indicated that of the 333 patients with HCC, those who carried ADAM10 rs514049 (AC + CC) variants had a higher risk of developing lymph node metastasis (odds ratio [OR] = 5.087, p = 0.027), and those who carried ADAM10 rs653765 (GA + AA) variants had a higher risk of developing distant metastasis (OR = 3.346, p = 0.020) and higher levels of α-fetoprotein. In conclusion, our study demonstrated that the SNPs of ADAM10 are involved in HCC progression. ADAM10 SNPs may be used as therapeutic targets to evaluate poor prognoses for HCC.

Fibroblast growth factor receptor 4 (FGFR4) plays a prominent role in cell proliferation and cancer progression. This study explored the effect of FGFR4 single-nucleotide polymorphisms (SNPs) on the clinicopathological characteristics of urothelial cell carcinoma (UCC). This study was conducted to survey the possible correlation of the polymorphism of FGFR4 to the risk and clinicopathologic characteristics of UCC. Four loci of FGFR4 (rs2011077 T > C, rs351855 G > A, rs7708357 G>A, and rs1966265 A > G) were genotyped via the TaqMan allelic discrimination approach in 428 UCC cases and 856 controls. The results indicated that UCC subjects who carried the SNP rs2011077 TC+CC genotypes were significantly related to a higher tumor stage (odds ratio (OR): 1.751, 95% confidence interval (CI): 1.078-2.846), primary tumor size (OR: 1.637, 95% CI: 1.006-2.662), and histopathologic grading (OR: 1.919, 95% CI: 1.049-3.511). Moreover, the SNP rs1966265 AG+GG genotypes were prominently related to a higher tumor stage (OR: 1.769, 95% CI: 1.082-2.891), primary tumor size (OR: 1.654, 95% CI: 1.011-2.706), and histopathologic grading (OR: 2.006, 95% CI: 1.096-3.674) compared to individuals with AA homozygotes. In conclusion, our data reveal association of FGFR4 polymorphisms with UCC clinicopathologic characteristics. FGFR4 polymorphisms may serve as a marker or therapeutic target in UCC development.

Prostate cancer is one of the major cancers of the genitourinary tract. High-mobility group box 1 (HMGB1) was suggested as a promising therapeutic target for prostate cancer. In this study, we aim to elucidate the associations of HMGB1 single nucleotide polymorphisms (SNPs) with prostate cancer susceptibility and clinicopathological characteristics. The HMGB1 SNPs rs1412125, rs2249825, rs1045411, and rs1360485 in 579 prostate cancer patients and 579 cancer-free controls were analyzed with real-time polymerase chain reactions (real-time PCR). All of the data were evaluated with SAS statistical software. Our results showed that the HMGB1 rs1045411 T allele genotype was significantly associated with advanced pathologic T stage (odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.021‒2.012; p = 0.037) and pathologic N1 stage (OR = 2.091, 95% CI = 1.160‒3.767; p = 0.012), and the rs1360485 polymorphic CT + TT genotype was associated with pathologic Gleason grade group (4 + 5) (OR = 1.583, 95% CI = 1.017‒2.462; p = 0.041), pathologic T stage (3 + 4) (OR = 1.482, 95% CI = 1.061‒2.070; p = 0.021), and pathologic N1 stage (OR = 2.131, 95% CI = 1.178‒3.852; p = 0.011) compared with their wild-type carriers. In conclusion, our results revealed that the HMGB1 SNPs were associated with the clinical status of prostate cancer. The HMGB1 SNPs may have the potential to predict prostate cancer disease progression.

Active surveillance is the preferred strategy for very low risk, low risk, and some favorable intermediate risk of prostate cancer. However, the current risk stratifications with initial prostate-specific antigen (iPSA) levels and Gleason scores at biopsy can underestimate the true oncologic threat. More precise predictors are required to avoid the overtreatment of prostate cancer. H19 single-nucleotide polymorphisms (SNPs) have been found to play crucial roles in numerous malignancies, but not yet in prostate cancer. This study assessed the clinicopathologic effects of H19 SNPs on prostate cancer to identify potential active surveillance candidates. A total of 579 patients with prostate cancer who underwent robot-assisted radical prostatectomy between 2012 and 2017 were recruited. The patients were grouped by iPSA levels, and five H19 SNPs were evaluated. Our results show that patients with an iPSA level of ≤7 ng/mL had increased an likelihood of having Gleason score and group grade upgrades after radical prostatectomy compared with patients with an iPSA level of >7 ng/mL. Moreover, patients with loci polymorphisms in either rs3024270 or rs3741219 had a significantly higher risk of perineural invasion (rs3024270: Odds ratio (OR) 2.76, 95% confidence interval (CI) 1.30-5.87, p = 0.01; rs3741219: OR 2.30, 95% CI 1.17-4.54, p = 0.018). In conclusion, our results suggested that H19 SNPs play a role in the perineural invasion of prostate cancer.

Lung adenocarcinoma is a subtype of lung cancer with high morbidity and mortality. CD44 is instrumental in many physiological and tumor pathological processes. The expression of unique single nucleotide polymorphisms (SNPs) contributes to protein dysfunction and influences cancer susceptibility. In the current study, we investigated the relationship between CD44 polymorphisms and the susceptibility to lung adenocarcinoma with or without epidermal growth factor receptor (EGFR) gene mutations. This study included 279 patients with lung adenocarcinoma. In total, six CD44 SNPs (rs1425802, rs11821102, rs10836347, rs13347, rs187115, and rs713330) were genotyped using a real-time polymerase chain reaction. We found no significant differences in genotype distribution of CD44 polymorphisms between EGFR wild-type and EGFR mutation type in patients with lung adenocarcinoma. We observed a strong association between CD44 rs11821102 G/A polymorphism and EGFR L858R mutation (odds ratio (OR) = 3.846, 95% confidence interval (CI) = 1.018-14.538; p = 0.037) compared with the EGFR wild-type group. In the subgroup of male patients with lung adenocarcinoma harboring the EGFR wild-type, both CD44 rs713330 T/C (OR = 4.317, 95% CI = 1.029-18.115; p = 0.035) and rs10836347 C/T polymorphisms (OR = 9.391, 95% CI = 1.061-83.136; p = 0.019) exhibited significant associations with tumor size and invasion. Data from the present study suggest that CD44 SNPs may help to predict cancer susceptibility and tumor growth in male patients with lung adenocarcinoma.

Urothelial cell carcinoma (UCC) is a common malignancy of the urinary tract in Taiwan. Metastasis-Associated in Colon Cancer 1 (MACC1), a newly identified oncogene and regulator of the HGF/Met signaling pathway, has been shown to play a critical role in the development and progression of several types of cancer. Our study aims to investigate the impact of MACC1 gene polymorphisms on the clinicopathological features of patients with UCC. In this study, we included a total of 719 patients with UCC and 719 healthy controls. The genotyping of five MACC1 gene polymorphisms (rs1990172, rs975263, rs3095007, rs4721888, and rs3735615) was performed using real-time PCR with TaqMan assays. Our findings indicate that urothelial cancer patients with MACC1 rs3095007 A allele had a decreased risk of >T2 stage [Odds ratio (OR)=0.619, 95% CI=0.394-0.971, p=0.036] and lymph node invasion (OR=0.448, 95% CI=0.201-0.998, p=0.044). Additionally, these individuals were associated with longer relapse-free survival (p=0.007) and overall survival (p=0.028). In conclusion, our findings demonstrate that urothelial cancer patients with MACC1 (rs3095007) CA and AA genotypes have a lower risk of advanced T stage and lymph node metastasis. Additionally, these genotypes were associated with longer relapse-free survival and overall survival, highlighting the potential of these biomarkers as predictors of UCC prognosis.

Lung adenocarcinoma (LADC) is the most common subtype of lung cancer worldwide and the epidermal growth factor receptor (EGFR) has a great influence on its clinical course, mainly due to the influence of different phenotypes. The Aurora kinase A (AURKA) would influence the progression of several solid malignancies. However, whether the interaction between EGFR phenotypes and AURKA would influence the clinical characteristics of LADC remains unknown. Herein, this study aimed to explore the effects of single-nucleotide polymorphisms (SNPs) of AURKA and EGFR phenotypes on the clinicopathological characteristics of LADC. Four loci of AURKA SNPs (rs1047972, rs2273535, rs6024836, and rs2064863) were genotyped using TaqMan allelic discrimination in 105 wild-type EGFR individuals and 167 LADC patients with EGFR mutations. After the statistical analysis, patients with LADC who had CT heterozygotes of AURKA rs1047972 had a lower risk of EGFR mutations than patients with wild-type homozygotes. Moreover, female and nonsmoking patients who carried the CT genotype of AURKA rs1047972 had a lower risk of EGFR mutation (p = 0.008 and p = 0.004, respectively). Moreover, in patients with EGFR mutations, AURKA SNP rs6024836 G allele (AG + GG) carriers had a lower risk of developing advanced-stage LADC (stage III or IV; odds ratio = 0.423, 95% confidence interval: 0.203-0.879, p = 0.019) than patients with AA homozygotes. Our results suggested that AURKA rs1047972 variants are significantly associated with EGFR mutations among patients with LADC, particularly in female and nonsmoking patients. AURKA variants may contribute to the pathological development of LADC.

The purposes of the current study were conducted to explore the relationships among long non-coding RNA gene H19 (LncRNA H19) polymorphisms and clinicopathological characteristics of uterine cervical cancer, and patient prognosis in Taiwan. Five genetic variants of LncRNA H19 rs3024270, rs2839698, rs3741219, rs2107425 and rs217727 were recruited from one hundred and thirty-four patients with invasive cancer, 101 with high-grade cervical intraepithelial neoplasia (CIN) of uterine cervix and 325 controls and their genetic distributions were determined. It indicated no associations of these LncRNA H19 genetic variants with development of cervical cancer. CC/CT in LncRNA H19 rs2839698 exhibited less risk to have pelvic lymph node metastasis [Odds ratio (OR): 0.19, 95% Confidence interval (CI):0.04-0.82, p=0.028)], as compared with TT. Meanwhile, cervical cancer patients with AA/AG in rs3741219 also had less risk to develop pelvic lymph node metastasis (OR: 0.17, 95% CI: 0.05-0.63, p=0.008), large tumor (OR: 0.17, 95% CI: 0.04-0.82, p=0.014) as well as parametrium (OR: 0.26, 95% CI: 0.07-0.95, p=0.045) and vagina invasion (OR: 0.25, 95% CI: 0.07-0.91, p=0.041, as compared to those with GG. However, only positive pelvic lymph node metastasis was related to worse recurrence-free survival and poor overall survival. Conclusively, it indicated no association of LncRNA H19 SNPs with cervical carcinogensis in Taiwanese women. Although genotypes TT in LncRNA H19 rs2839698 and GG in rs3741219 are related to some poor clinicopathological parameters of cervical cancer, only pelvic lymph node status could predict 5 year patient survival significantly.

We investigated the association between interleukin-18 (IL-18) polymorphisms and the susceptibility and clinicopathological state of hepatocellular carcinoma (HCC). In total, 901 participants, including 559 healthy controls and 342 patients with HCC, were recruited. The allelic discrimination of -607A/C (rs1946518) and -137G/C (rs187238) polymorphisms of IL-18 was assessed through real-time polymerase chain reaction by performing the TaqMan assay. The IL-18 -137G/C polymorphism but not the -607A/C polymorphism showed a significant association with the risk of HCC. Participants carrying the IL-18 -137 polymorphism with heterozygous G/C and homozygous CC genotypes showed a 1.987-fold increase (95% CI = 1.301-3.032; p = 0.001) in the risk of HCC compared with those homozygous for wild-type G/G. The 342 patients with HCC carrying the IL-18 -137G/C polymorphism were positive for hepatitis B virus (HBV) infection with an adjusted odds ratio of 1.668. Moreover, the 142 HBV positive patients with HCC and the IL-18 -137 polymorphism were positive for at least one C genotype and showed significant vascular invasion (p = 0.018). Furthermore, the level of α-fetoprotein was high in the patients carrying the IL-18 -137 polymorphism with GC+CC alleles (p = 0.011). In conclusion, the IL-18 -137G/C polymorphism with a GC+CC genotype could be a factor that increases the risk of HCC. Furthermore, the correlation between the IL-18 -137G/C polymorphism and HCC-related HBV infection is a risk factor for vascular invasion and has a synergistic effect that can further enhance HCC prognosis.

Increasing evidence shows that dysregulated expression of long non-coding (lnc)RNAs can serve as diagnostic or prognostic markers in urothelial cell carcinoma (UCC), the most common pathological type of bladder cancer. lncRNA HOX transcript antisense RNA (HOTAIR) was shown to promote tumor progression and be associated with a poor prognosis in multiple cancers including bladder cancer. Polymorphisms of HOTAIR were recently linked to a predisposition for diverse malignancies. Herein we conducted a case-control study to evaluate whether genetic polymorphisms of HOTAIR were associated with UCC risk and clinicopathologic characteristics. Four loci (rs920778 T>C, rs1899663 G>T, rs4759314 A>G, and rs12427129, C>T) of HOTAIR were genotyped by a TaqMan allelic discrimination method in 431 cases and 862 controls. We found that female patients who carried AG + GG genotype of rs4759314 were associated with an increased UCC risk after controlling for age and tobacco consumption (adjusted odds ratio (AOR) = 1.92, 95% confidence interval (CI): 1.01⁻3.64, p = 0.047) and a lower overall survival rate (p = 0.008). Moreover, patients with a smoking habit or younger age (≤65 years), who had at least one T allele of HOTAIR rs12427129 were at a higher risk of developing advance tumor T satge (p = 0.046), compared to those patients with CC homozygotes. In contrast, rs920778 C allele carriers were negatively correlated with the development of lymph node metastasis (OR = 0.51, 95% CI: 0.28⁻0.94, p = 0.031). Further analyses of clinical datasets revealed correlations of the expression of HOTAIR with tumor metastasis and a poor survival rate in patients with UCC. Our results verified the diverse impacts of HOTAIR variants on UCC susceptibility and clinicopathologic characteristics.

The aim of the current study is to evaluate the possible correlation between the single-nucleotide polymorphisms (SNP) of HOX transcript antisense intergenic RNA (HOTAIR) and the clinical characteristics of diabetic retinopathy (DR). Four loci of HOTAIR SNPs, including rs920778 (T/C), rs12427129 (C/T), rs4759314 (A/G), and rs1899663 (G/T), were genotyped via the TaqMan allelic discrimination for 276 DR individuals and 452 non-DR patients. The distribution frequency of HOTAIR SNP rs12427129 CT [adjusted odds ratio (AOR): 1.571, 95% CI: 1.025-2.408, p = 0.038], HOTAIR SNP rs12427129 CT+TT (AOR: 1.611, 95% CI: 1.061-2.446, p = 0.025), and HOTAIR SNP rs1899663 TT (AOR: 2.443, 95% CI: 1.066-5.595, p = 0.035) were significantly higher in the DR group. Moreover, the proliferative diabetic retinopathy (PDR) subgroup revealed a significantly higher distribution of HOTAIR SNP rs12427129 CT+TT (AOR: 2.016, 95% CI: 1.096-3.710, p = 0.024) and HOTAIR SNP rs1899663 TT (AOR: 4.693, 95% CI: 1.765-12.479, p = 0.002), and the distribution frequencies of HOTAIR SNP rs12427129 CT (AOR: 3.722, 95% CI: 1.555-8.909, p = 0.003), HOTAIR SNP rs12427129 CT+TT (AOR: 4.070, 95% CI: 1.725-9.600, p = 0.001), and HOTAIR SNP rs1899663 TT (AOR: 11.131, 95% CI: 1.521-81.490, p = 0.018) were significantly higher in the female PDR subgroup. Regarding the clinical characters, the DR patients with HOTAIR SNP rs1899663 GT+TT revealed a significantly shorter duration of diabetes compared to the DR patients with HOTAIR SNP rs1899663 GG (10.54 ± 8.19 versus 12.79 ± 7.73, p = 0.024). In conclusion, HOTAIR SNP rs12427129 and rs1899663 are strongly correlated to the presence of DR, especially for a female with PDR.

The principal pathogenesis of coronary artery disease (CAD) is coronary artery atherosclerosis, a chronic inflammatory disease of the vessel walls of the coronary artery. Intercellular adhesion molecule-1 (ICAM-1) displays an important role in the development of the inflammation reaction and atherosclerosis. Few studies report the association of ICAM-1 genetic polymorphisms with CAD in Taiwanese subjects. Therefore, we conducted a study to associate the single nucleotide polymorphisms (SNPs) of ICAM-1, rs5491, rs5498, rs281432 and rs3093030 with CAD. Five hundred and twenty-five male and female subjects, who received elective coronary angiography in Taiwan Chung Shan Medical University Hospital, were recruited to determine four ICAM-1 SNPs by real time-polymerase chain reaction and genotyping. The relationships among ICAM-1 SNPs, haplotypes, demographic and characteristics and CAD were analyzed. This study showed that rs281432 (C8823G) was the only ICAM-1 SNP which affect the development of CAD. Multivariate analysis revealed that ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], male gender (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), aspirin use in the past 7 days (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), hypertension (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), serum cardiac troponin I elevation (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) and severe angina in recent 24 hours (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) increase the risk of CAD. In conclusion, ICAM-1 SNP rs281432 is an independent factor to predict the development of CAD. ICAM-1 SNP rs281432 homozygotic mutant GG can reduce the susceptibility to the CAD in Taiwanese subjects.

Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A>G, rs3829078 A>G, and rs1048638 C>A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16-0.95, p = 0.039) and AG+GG (AOR: 0.43, 95% CI: 0.18-0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG+GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG+GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.

Lung adenocarcinoma (LADC) is a major subtype of lung cancer, particularly among populations of East Asia. The epidermal growth factor receptor (EGFR) is the most frequently mutated oncogene promoting LADC progression and can serve as a therapeutic target in LADC. The tissue inhibitor of metalloproteinases (TIMP)-3 is a major regulator of extracellular matrix turnover via targeting of matrix metalloproteinases (MMPs), and thus, plays a critical role in tumor development and progression. The purpose of this study was to investigate potential associations among TIMP-3 genetic polymorphisms, EGFR statuses, and cancer clinicopathologic development in patients with LADC. In this study, 277 LADC patients with different EGFR statuses were recruited to dissect the allelic discrimination of TIMP-3 -1296 T>C (rs9619311), TIMP3 249T>C (rs9862), and TIMP3 261C>T (rs11547635) polymorphisms using a TaqMan allelic discrimination assay. Our data showed that compared to those LADC patients with wild-type CC homozygotes of TIMP-3 rs9862, patients harboring TT homozygotes of rs9862 were at a higher risk of developing mutant EGFR (adjusted odds ratio (AOR) = 2.530; 95% confidence interval (CI): 1.230-5.205; p = 0.012), particularly the EGFR L858R point mutation (AOR = 2.975; 95% CI: 1.182-7.488; p = 0.021). Moreover, we observed that TIMP-3 TT homozygotes of rs9862 were correlated with the incidence of EGFR mutations in patients with a smoking habit (p = 0.045). Within male patients harboring a mutant EGFR, TIMP-3 rs9862 T (CT+TT) allele carriers were at higher risk of developing an advanced stage (p = 0.025) and lymph node metastasis (p = 0.043). Further analyses of clinical datasets revealed correlations of TIMP-3 expression with a favorable prognosis in patients with LADC. In conclusion, the data suggest that TIMP-3 rs9862 polymorphisms may contribute to identify subgroups of lung cancer patients at high risk for tumor progression, among carriers of LADC-bearing mutant EGFR.

Dopamine receptor D2 (DRD2) is overexpressed in several kinds of cancers and was correlated with the prognosis of these cancers. Polymorphisms within the DRD2 gene were shown to be associated with lung and colon cancers. The purpose of this study was to explore effects of DRD2 gene polymorphisms on the susceptibility to and clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 369 patients diagnosed with UCC and 738 healthy controls were enrolled to analyze DRD2 genotypes at four loci (rs1799732, -141C>del; rs1079597, TaqIB; rs6277, 957C>T; and rs1800497, TaqIA) using a TaqMan-based real-time polymerase chain reaction (PCR). We found a significantly lower risk for UCC in individuals with the DRD2 rs6277 CT genotype compared to those with the wild-type CC genotype (adjusted odds ratio (AOR)=0.405, 95% confidence interval (CI): 0.196~0.837, p=0.015). In 124 younger patients (aged < 65 years) of the recruited UCC cohort, patients who carried at least one T allele of DRD2 rs1800497 were at higher risk (AOR=2.270, 95% CI: 1.060~4.860, p=0.033) of developing an invasive stage (pT2~pT4). In 128 female patients of the recruited UCC cohort, patients who carried at least one deletion allele of DRD2 rs1799732 showed a higher incidence of having an invasive stage (AOR=2.585, 95% CI: 1.066~6.264, p=0.032) and a large tumor (AOR=2.778, 95% CI: 1.146~6.735, p=0.021). Further analyses of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed correlations of the expression of DRD2 with an invasive tumor, tumor metastasis, and the lower survival rate in patients with UCC. Our findings suggest that DRD2 levels might affect the progression of UCC, and the polymorphisms rs6277, rs1800497, and rs1799732 of DRD2 are probably associated with the susceptibility and clinicopathologic development of UCC in a Taiwanese population.