BACKGROUND/AIM:Pterygium is a common ocular surface disorder associated with long-term ultraviolet exposure and/or oxidative DNA damage. Accumulated evidence suggests that defects in DNA repair pathways may contribute to pterygium risk. DNA ligase I (LIG1), a key enzyme involved in DNA replication and base excision repair, has been involved in the etiology of several human diseases, including cancers. However, its role in pterygium has never been examined before. This study aimed at exploring the association between the LIG1 genotypes and pterygium risk in a Taiwanese population. PATIENTS AND METHODS:The hospital-based case-control study was conducted including 165 patients with pterygium and 320 age- and sex-matched non-pterygium controls. LIG1 rs20579 genotypes were accessed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Stratified analysis and the calculation of odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used for evaluating the associations between genotypes and pterygium risk. RESULTS:Individuals carrying the homozygous variant AA genotype exhibited a significantly elevated risk of pterygium compared with those carrying the GG genotype (OR=2.74, 95% CI=1.17-6.43, p=0.0305). Under the recessive model, the AA genotype conferred a 2.65-fold elevated risk (95% CI=1.14-6.18, p=0.0350). The variant A allele was also associated with increased susceptibility (OR=1.46, 95% CI=1.03-2.07, p=0.0413). Stratified analyses revealed significant associations specifically among individuals aged ≥60 years (OR=5.64, 95% CI=1.67-19.04, p=0.0039) and males (OR=5.23, 95% CI=1.74-15.73, p=0.0034), but not those of younger ages or females. CONCLUSION:The LIG1 rs20579 genotype is significantly associated with pterygium susceptibility in Taiwanese individuals, particularly among elderly and male subjects. These findings support the involvement of impaired DNA repair machinery in pterygium pathogenesis and suggest that LIG1 rs20579 may serve as a novel genetic biomarker for risk assessment and early detection of pterygium.

BACKGROUND/AIM:Pterygium is a chronic, fibrovascular ocular surface disorder with tumor-like biological behavior. Although inflammatory mediators such as interleukin-17 (IL17) are increasingly implicated in its pathogenesis, the genetic contribution of IL17 remain unclear. To our knowledge, this study is the first to investigate whether IL17A rs2275913 and IL17F rs763780 polymorphisms influence pterygium susceptibility in a Taiwanese population. MATERIALS AND METHODS:This case-control study evaluated the association between promoter IL17A rs2275913 and exonic IL17F rs763780 polymorphisms with pterygium susceptibility in 160 patients and 320 age- and sex-matched controls by polymerase chain reaction-restriction fragment length polymorphism methods. The potential interactions between IL17A genotype and age or sex were tested by stratified analysis. RESULTS:IL17A rs2275913 genotype distribution showed borderline overall significance (p for trend=0.0522). Compared with GG carriers, individuals with AG and AA genotypes exhibited odds ratios (ORs) 1.39 [95% confidence interval (CI)=0.91-2.13, p=0.1546] and 1.92 (95%CI=1.11-3.30, p=0.0263), respectively. Under the dominant model (AG+AA vs. GG), risk of pterygium was increased significantly (OR=1.53, 95% CI=1.03-2.27, p=0.0449). The A allele conferred elevated susceptibility (OR=1.42, 95% CI=1.08-1.87, p=0.0136). No significant associations were observed for IL17F rs763780 (all p>0.05). Stratified analyses indicated significant increased effects of IL17A rs2275913 genotype by older age (≥60 years), and female sex. CONCLUSION:Our findings demonstrate, for the first time, that IL17A rs2275913, particularly the A allele and AA genotype, is associated with increased pterygium risk among Taiwanese individuals, with stronger effects among older adults and females. These results suggest a potential genetic basis for IL17-mediated inflammation in pterygium and highlight IL17A rs2275913 as a promising biomarker for pterygium susceptibility.

BACKGROUND/AIM:Renal cell carcinoma (RCC) accounts for more than 90% of kidney malignancies worldwide. Matrix metalloproteinase-2 (MMP-2) has been reported to be dysregulated in multiple cancers. However, the relationship between MMP-2 genetic polymorphisms and RCC risk has rarely been investigated. This study aimed to evaluate the associations of two promoter polymorphisms, MMP-2 rs243865 and rs2285053, with RCC susceptibility in a Taiwanese population. MATERIALS AND METHODS:A hospital-based case-control study was conducted including 118 RCC patients and 590 cancer-free controls. Genotyping of MMP-2 rs243865 and rs2285053 was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS:A significant association was observed between MMP-2 rs243865 and RCC susceptibility (p for trend=0.0077). Compared to the CC genotype, individuals carrying the TT genotype exhibited a markedly increased risk of RCC (OR=4.29, 95%CI=1.56-11.83, p=0.0069), whereas the CT genotype showed no significant effect (OR=1.31, 95%CI=0.80-2.16, p=0.3530). The T allele was also associated with elevated RCC risk (OR=1.71, 95%CI=1.15-2.54, p=0.0101). In contrast, rs2285053 showed no significant association with RCC. Stratified analyses revealed significant MMP-2 rs243865 genotype differences among subgroups defined by smoking, alcohol consumption, and hypertension status (p=0.0175, 0.0173, and 0.0063, respectively). CONCLUSION:MMP-2 rs243865, particularly the TT genotype, may serve as a genetic susceptibility marker for RCC and may interact with lifestyle and clinical factors including smoking, alcohol drinking, and hypertension. Further large-scale studies are warranted to validate these observations and clarify the biological mechanisms underlying MMP-2-mediated RCC carcinogenesis.

BACKGROUND/AIM:Pterygium is a chronic fibrovascular ocular surface disorder with multifactorial etiology involving environmental and genetic factors. Given the tumor-like characteristics of pterygium, the cell cycle regulator cyclin dependent kinase inhibitor 1A (CDKN1A) has been proposed as a potential contributor. This study aimed to investigate the association between CDKN1A rs1801270 and rs1059234 polymorphisms and pterygium susceptibility. MATERIALS AND METHODS:The distributions of genotypic patterns of CDKN1A rs1801270 and rs1059234 among 160 pterygium cases and 320 controls were determined using chain reaction-restriction fragment length polymorphism methods. The potential interactions between CDKN1A genotype and age or sex were tested by stratified analysis. RESULTS:No significant differences in genotype distributions were observed between cases and controls for rs1801270 (p=0.5493) or rs1059234 (p=0.5842). Stratified analyses indicated reducing effects of CDKN1A rs1801270 AA genotype by older age (≥60 years) [odds ratio (OR)=0.38, 95% confidence interval (CI)=0.18-0.82, p=0.0204] or female sex (OR=0.37, 95%CI=0.16-0.86, p=0.0307) on pterygium risk. No association was found for rs1059234 in similar stratified analyses (all p>0.05). CONCLUSION:Although CDKN1A polymorphisms were not associated with pterygium susceptibility, rs1801270 may serve as a protective marker in female and elder subgroups. These findings suggest a context-dependent role of CDKN1A in pterygium pathogenesis, which needs further validation.

BACKGROUND/AIM:Bladder cancer (BLCA) is a prevalent malignancy globally, particularly in Taiwan, where its incidence continues to rise. While environmental exposures such as smoking play critical roles in BLCA etiology, genetic predispositions also contribute significantly. Matrix metalloproteinase-2 (MMP-2), a key enzyme involved in extracellular matrix remodeling, has been implicated in BLCA progression. This study investigated the associations of two promoter polymorphisms in the MMP-2 gene, rs243865 and rs2285053, with BLCA susceptibility in a Taiwanese population. PATIENTS AND METHODS:A case-control study was conducted involving 375 BLCA patients and 375 cancer-free controls matched by age and sex. Genotyping was performed using PCR-RFLP, and associations with BLCA risk were evaluated using logistic regression, adjusting for confounders. Stratified analyses were performed based on demographic and clinical parameters. RESULTS:No significant association was observed between rs243865 and overall BLCA risk (OR=1.34, 95%CI=0.96-1.86, p=0.0953). In contrast, rs2285053 showed a significant allelic association with BLCA (OR=1.33, 95%CI=1.04-1.69, p=0.0263). Stratified analysis revealed that younger individuals (≤55 years) carrying the CT genotype of rs243865 had a significantly elevated BLCA risk (OR=2.48, 95%CI=1.39-4.42, p=0.0028). Among smokers, both CT and TT genotypes of rs2285053 were associated with increased risk (OR=1.68 and 4.01, p=0.0214 and 0.0045). Additionally, rs243865 TT genotype was associated with muscle-invasive BLCA (OR=3.68, 95%CI=1.96-6.91, p=0.0001). CONCLUSION:MMP-2 rs2285053 and, to a lesser extent, rs243865 polymorphisms may influence BLCA susceptibility and aggressiveness, particularly in the context of age and smoking. These variants may serve as potential biomarkers for personalized risk assessment, pending validation in larger, multiethnic cohorts.

BACKGROUND/AIM:Gastric cancer (GACA) is a major global health burden, ranking fifth in incidence and third in cancer-related mortality worldwide. Despite growing knowledge of environmental risk factors such as Helicobacter pylori infection, smoking, and alcohol consumption, the role of genetic susceptibility, particularly polymorphisms in matrix metalloproteinase-11 (MMP-11), in GACA pathogenesis remains unclear. MATERIALS AND METHODS:We conducted a hospital-based case-control study involving 161 patients with GACA and 483 age- and sex-matched cancer-free controls of Taiwanese ethnicity. Four MMP-11 single nucleotide polymorphisms (SNPs), rs738791, rs2267029, rs738792, and rs28382575, were genotyped using PCR-RFLP and direct sequencing. Logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with a significance threshold of p<0.05. RESULTS:Overall, no significant associations were observed between MMP-11 SNPs and GACA susceptibility. However, the rs28382575 C allele was associated with increased risk (p=0.0377). Stratified analysis revealed that rs738791 CT/TT genotypes were significantly associated with metastasis (p=0.0129). Among smokers and drinkers, rs28382575 CT/CC genotypes conferred elevated risk (smokers: p=0.0027; drinkers: p=0.0153), while rs738792 variant genotypes appeared protective (smokers: p=0.0124; drinkers: p=0.0022). CONCLUSION:While MMP-11 polymorphisms are not suitable as population-level screening markers for GACA risk, rs738791 and rs28382575 may serve as predictors for metastasis, and rs28382575 and rs738792 as modifiers of gene-environment interaction. Functional validation is warranted to elucidate the biological relevance of these findings in GACA progression.

BACKGROUND/AIM:Lung cancer remains the leading cause of cancer-related mortality worldwide, and cigarette smoking is its predominant factor. However, genetic biomarkers contributing to susceptibility, particularly within cell-cycle regulatory genes such as cyclin dependent kinase inhibitor 1B (CDKN1B), remain incompletely identified. The study aimed to investigate the contribution of CDKN1B rs34330 and rs2066827 polymorphisms to lung cancer risk, and to evaluate their interaction with smoking behavior in a Taiwanese cohort. MATERIALS AND METHODS:The CDKN1B genotypes of 358 lung cancer patients and 716 healthy controls were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Genotypic and allelic distributions were compared using chi-square tests, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Stratified analyses were performed according to smoking status. RESULTS:No significant association was observed between CT (OR=1.20, 95%CI=0.87-1.66, p=0.2928) or TT (OR=1.26, 95%CI=0.87-1.83, p=0.2656) rs34330 genotypes and lung cancer risk. Similarly, in dominant (OR=1.22, 95%CI=0.90-1.66, p=0.2302) and recessive models (OR=1.11, 95%CI=0.82-1.49, p=0.5576), no significant association were found. Allelic analysis confirmed no difference for rs34330 T allele (p=0.2654) or rs2066827 G allele (p=0.8868). However, among smokers, rs34330 TT genotype carriers exhibited significantly elevated lung cancer risk (OR=1.59, 95%CI=1.05-2.42, p=0.0372), persisting after adjustment for age and sex (OR=1.64, 95%CI=1.07-2.36). This is not found among non-smokers. CONCLUSION:Although CDKN1B polymorphisms are not independently associated with lung cancer susceptibility, rs34330 may interact with cigarette smoking to elevate its risk. These findings suggest a potential gene-environment interaction influencing smoking-related lung carcinogenesis and warrant further validation in larger multi-ethnic populations.

Introduction: Genetic polymorphisms in DNA repair pathways can modulate DNA repair capacity and influence susceptibility to aging-related disorders, including Parkinson's disease (PD). This study evaluated the association between the DNA ligase I rs20579 polymorphism and PD risk. Materials and methods: Genotyping of DNA ligase I rs20579 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 123 PD patients and 492 age-and sex-matched controls of Taiwanese Han ethnicity. Associations between rs20579 genotypes and PD risk were analyzed. Results: Among controls, the genotype distribution of rs20579 was 78.7 % GG, 19.3 % AG, and 2.0 % AA, compared with 75.6 %, 21.1 %, and 3.3 % among PD cases, respectively (p for trend = 0.6290). No significant differences were observed in the prevalence of AG (p = 0.6939) or AA (p = 0.4908) genotypes between cases and controls. Allelic analysis showed a non-significant increase in PD risk for A allele carriers (OR = 1.21, 95 % CI = 0.80-1.83, p = 0.4189). Stratified analysis revealed no significant genotype differences among males. In females, the AA genotype was associated with a borderline increased risk of PD (OR = 1.86, 95 % CI = 1.00-3.47, p = 0.0526). Conclusion: In this Taiwanese Han cohort, the DNA ligase I rs20579 A allele may be a genetic marker of increased PD susceptibility in females. Further studies in larger, independent populations are warranted to confirm its clinical relevance.

BACKGROUND/AIM:Pterygium is a common ocular surface disorder with multifactorial etiology involving environmental exposure and immune dysregulation. Interleukin-12 (IL-12), a key immunomodulatory cytokine, has been implicated in inflammation and tumor-related processes, yet its genetic contribution to pterygium remains unclear. This study aimed to evaluate the association between IL-12A polymorphisms and pterygium susceptibility. MATERIALS AND METHODS:A hospital-based case-control study was conducted, including 160 pterygium patients and 320 age- and sex-matched controls. Genotyping of IL-12A rs568408 and rs2243115 was performed via restriction fragment length polymorphism methods. RESULTS:Both polymorphisms were in Hardy-Weinberg equilibrium among controls (p=0.2165 and p=0.5533). No significant differences in genotype distributions were observed between cases and controls for rs568408 (p for trend=0.5727) or rs2243115 (p for trend=0.5471). The rs568408 AG and AA genotypes showed non-significant associations with pterygium risk (OR=1.14, 95%CI=0.72-1.78, p=0.6603; OR=1.63, 95% CI=0.59-4.49, p=0.4950). Similarly, allelic analyses revealed no significant associations (as for rs568408, OR=1.21, 95%CI=0.84-1.76, p=0.3527; as for rs2243115, OR=1.27, 95%CI=0.81-2.01, p=0.3581). CONCLUSION:Despite the tumor-like and inflammatory characteristics of pterygium, IL-12A polymorphisms were not significantly associated with disease susceptibility. However, IL-12-mediated immune pathways may still contribute to disease pathogenesis through functional regulation rather than genetic variation. Further large-scale and mechanistic studies are warranted.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and α-synuclein aggregation, with evidence implicating impaired DNA double-strand break (DSB) repair in disease pathogenesis. This study aimed to systematically evaluate the association between genetic polymorphisms in DSB repair pathway genes, including XRCC4, XRCC5, XRCC6, XRCC7, LIG4, MRE11, RAD50, and NBN, and PD risk, along with corresponding mRNA expression and DNA repair capacity. A total of 123 clinically diagnosed PD patients and 492 age- and sex-matched healthy controls of Taiwanese ancestry were genotyped, and transcriptional and functional assays were performed in 52 healthy controls. Nominally significant associations with PD risk were identified for four SNPs: XRCC6 rs5751129 (p = 3.55 × 10⁻⁵), XRCC4 rs28360071 (p = 0.0181), NBN rs2735383 (p = 0.0213) and RAD50 rs17772583 (p = 0.0411). Among these, XRCC6 rs5751129 remained statistically significant after correction for multiple comparisons. Compared to individuals with the wild-type TT genotype, carriers of the heterozygous variant (TC) and homozygous variant (CC) genotypes exhibited increased PD risks, with odds ratios of 1.86 (95% CI, 1.09–3.17) and 13.82 (95% CI, 2.74–69.54), respectively. Cumulative analysis revealed a dose-dependent increase in PD risk with multiple high-risk genotypes (p for trend = 0.0025). Functionally, the XRCC6 rs5751129 CC variant was associated with reduced mRNA expression (p = 0.0001) and impaired NHEJ and DSB repair capacity (p = 0.0183). These findings suggest that genetic variants in DSB genes XRCC6, XRCC4, NBN and RAD50 are associated with PD susceptibility in a Taiwanese population and provide preliminary functional evidence that XRCC6 variants contribute to compromised DNA repair. Together, the results highlight a critical role of inherited DSB repair deficiencies in PD etiology and suggest potential avenues for personalized risk prediction and prevention.

Asthma is a chronic inflammatory airway disorder influenced by genetic and environmental factors. Matrix metalloproteinase-12 (MMP-12) plays a key role in airway remodeling and inflammation, but its genetic contribution to asthma remains unclear. This study investigated the associations of MMP-12 rs2276109 and rs652438 polymorphisms with asthma susceptibility and severity in 198 Taiwanese asthma patients and 453 controls. Genotypes were determined by PCR-RFLP, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Neither MMP-12 rs2276109 nor rs652438 was significantly associated with overall asthma susceptibility. For rs2276109, the CT and CC genotypes yielded ORs of 1.06 (95% CI = 0.56–2.00, p = 0.9913) and 6.98 (95% CI = 0.72–67.59, p = 0.0857), respectively. However, among individuals aged 25–40 years, rs652438 CT and CC genotypes were associated with elevated asthma risk (OR = 1.86, 95% CI = 1.14–3.04, p = 0.0100; OR = 3.60, 95% CI = 1.11–11.65, p = 0.0494). Furthermore, MMP-12 rs652438 was significantly associated with asthma severity under both the CT genotype (OR = 2.32, 95% CI = 1.16–4.62, p = 0.0250) and dominant models (OR = 2.45, 95% CI = 1.28–4.72, p = 0.0106). Although MMP-12 polymorphisms do not appear to influence overall asthma susceptibility, rs652438 may serve as a genetic marker for disease severity and clinical stratification in asthma.

BACKGROUND/AIM:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Matrix metalloproteinase-2 (MMP-2) plays an important role in extracellular matrix remodeling and HCC progression. This study investigated the associations of two functional MMP-2 promoter polymorphisms, rs243865 and rs2285053, with HCC susceptibility in a Taiwanese population and explored their potential interactions with environmental risk factors. MATERIALS AND METHODS:A hospital-based case-control study was conducted at China Medical University Hospital (Taichung, Taiwan), involving 298 HCC patients and 889 age- and sex-matched cancer-free controls recruited in Taiwan. MMP-2 rs243865 and rs2285053 genotypes were determined utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Stratified analyses were used to explore their potential interactions between MMP-2 genotypes and environmental factors including sex, smoking and alcohol drinking status. RESULTS:No significant association was observed between HCC susceptibility and either rs243865 (CT+TT versus CC: odds ratio (OR)=1.20, 95% confidence interval (CI)=0.87-1.66, p=0.2944] or rs2285053 (CT+TT versus CC: OR=1.12, 95% CI=0.86-1.46, p=0.4219). Similarly, allelic analyses revealed no significant effects. Interestingly, stratified analyses demonstrated significant gene-environment interactions for rs243865. Male carriers of the TT genotype exhibited an increased HCC risk (OR=3.24, 95% CI=1.12-9.37, p=0.0488). Among smokers, the TT genotype was associated with a markedly elevated risk (OR=6.46, 95% CI=1.65-25.29, p=0.0055), while alcohol drinkers carrying the TT genotype showed the highest susceptibility (OR=9.69, 95% CI=1.99-47.13, p=0.0022). No significant association was found for rs2285053 genotype in any genetic variant and subgroup. CONCLUSION:Although MMP-2 rs243865 and rs2285053 do not independently determine HCC susceptibility, rs243865 T allele may serve as a genetic biomarker for identifying Taiwanese males, smokers, and alcohol drinkers at elevated risk of HCC. These findings highlight the importance of gene-environment interactions in hepatocarcinogenesis and support the incorporation of genetic information into personalized HCC risk assessment and prediction strategies.

BACKGROUND/AIM:Pterygium is a fibrovascular ocular disease characterized by extracellular matrix (ECM) remodeling. Matrix metalloproteinase-3 (MMP-3), a key ECM-modulating enzyme, has been implicated to involved in pterygium progression, but its genetic marker has never been explored. This hospital-based case-control study investigated the association between MMP-3 polymorphisms and pterygium risk in a Taiwanese cohort. PATIENTS AND METHODS:Up to five MMP-3 genotypic patterns (rs3025058, rs522616, rs591058, rs650108, and rs679620) were identified among 160 pterygium cases and 320 age- and sex-matched controls. RESULTS:The MMP-3 rs3025058 5A allele was significantly associated with an elevated risk of pterygium (OR=1.94, 95%CI=1.39-2.71, p=0.0001). Compared to the wild-type 6A/6A genotype, individuals carrying MMP-3 5A/6A and 5A/5A exhibited a 1.66-fold and 4.36-fold elevated risk, respectively (p=0.0253 and 0.0014). Particularly, MMP-3 rs3025058 5A/5A genotype was significantly associated with elevated pterygium risk among elder (≥60 years old) individuals (p=0.0003). Furthermore, transcriptional and translational analyses revealed higher MMP-3 expression in carriers of the 5A allele, with the highest levels observed in 5A/5A homozygotes (all p<0.05). No significant associations were observed for the remaining four MMP-3 polymorphic variants. CONCLUSION:MMP-3 rs3025058 may serve as a genetic biomarker for pterygium susceptibility prediction, potentially contributing to ECM dysregulation and disease progression.

BACKGROUND/AIM:Oral cancer represents a major health burden in Taiwan, with tobacco use, alcohol consumption, and betel quid chewing recognized as predominant environmental risk factors. Matrix metalloproteinase-9 (MMP-9) has been implicated in tumor invasion and progression, and the promoter polymorphism rs3918242 has been investigated as a potential genetic determinant of cancer susceptibility. The study aims to reveal the contribution of MMP-9 genotypes to oral cancer susceptibility. MATERIALS AND METHODS:In this case-control study, 958 Taiwanese patients with histologically confirmed oral cancer and 958 cancer-free controls were genotyped for MMP-9 rs3918242 using PCR-RFLP. The association was evaluated via chi-square with Yates' correction in addition to odds ratio (OR) and corresponding 95% confidence interval (CI). RESULTS:The control group exhibited genotype frequencies consistent with the Hardy-Weinberg equilibrium (p=0.3192). Overall, no statistically significant association was observed between MMP-9 genotypes heterozygous CT (OR=1.09, 95%CI=0.89-1.36, p=0.4128) or homozygous TT (OR=1.65, 95%CI=0.96-2.84, p=0.0910) and oral cancer risk. Recessive and dominant genetic models similarly revealed no significant associations (OR=1.61 and 1.15, 95% CI=0.94-2.77 and 0.94-1.41, p=0.1066 and 0.1968). Allelic analysis also indicated no significant effect of the T allele on oral cancer susceptibility (OR=1.17, 95%CI=0.98-1.40, p=0.0843). Stratification by sex yielded non-significant associations in both males and females. Importantly, a gene-environment interaction analysis revealed that smokers carrying the TT genotype exhibited a significantly elevated risk of oral cancer (adjusted OR=1.91, 95% CI=1.04-3.88), whereas no interaction was observed with alcohol consumption or betel quid chewing. CONCLUSION:These findings suggest that while MMP-9 rs3918242 variants alone do not serve as reliable predictive biomarkers for oral cancer in Taiwanese, the TT genotype may synergize with cigarette smoking to increase susceptibility. Future studies in ethnically diverse populations, coupled with mechanistic investigations of MMP-9 expression in response to tobacco exposure, are warranted to elucidate the functional impact of this polymorphism in oral carcinogenesis.

Ovarian cancer is the most lethal gynecological malignancy worldwide, largely due to late diagnosis and lack of effective population-level screening tools. Inflammatory cytokines regulate proliferation, apoptosis, angiogenesis, and immune surveillance, making inherited variation in cytokine pathways biologically plausible determinants of ovarian cancer susceptibility and progression. Since the early 2000s, numerous candidate-gene studies have evaluated polymorphisms of genes such as the interleukin (IL) families, tumor necrosis factor alpha (TNFA), transforming growth factor beta 1 (TGFB1), and components of the nuclear factor kappa B (NFKB) signaling pathway and adhesion pathways, across diverse populations. In this review, we summarize these potential markers to give readers an overview showing accumulated evidence supports a coherent model in which genetically modulated inflammation is an integral driver of epithelial ovarian carcinogenesis. Collectively, studies reveal recurrent patterns of risk-increasing and risk-protective variants. Risky genotypes predicted to enhance pro-inflammatory, pro-angiogenic, or immunosuppressive signaling include IL1B rs16944 CC, IL6 rs1800795, IL8 rs2227306 TT, IL8 rs1126647 TT, IL16 rs11556218 GT/GG, IL16 rs4778889 CT/CC, IL23R rs10889677 AC/CC, IL31 rs4758680 CA/AA, IL32 rs28372698 TT, TNFA rs1800629 GA/AA, and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282 CG genotypes. Conversely, protective variants tend to dampen inflammatory tone or rebalance cytokine networks, including IL1A rs17561 GT/TT, IL1A rs4848300 CT/CC, IL1A rs3783553 insertion/insertion, IL1B rs7596684 CT/CC, IL6 rs1880242 GT/TT, IL31 rs7977932 CG/GG, TGFB1 rs1800469 CT/TT, selectin E (SELE) rs5361 AC, intercellular adhesion molecule 1 (ICAM1) rs5498 AG genotypes and specific IL6 haplotypes. Beyond risk per se, several polymorphisms appear predictive of clinical features, including tumor stage, cytoreductive resectability and recurrence, highlighting potential prognostic relevance. Notably, associations are often population-specific, reflecting differences in allelic frequencies and linkage disequilibrium across ethnic groups, underscoring the need for cross-ethnic replication. Further investigations may ultimately enable further improved the prevention, early detection, and personalized management of ovarian cancer.

BACKGROUND/AIM:Colorectal cancer (CRC) is a major global health burden with increasing incidence and significant mortality, particularly in advanced stages. Genetic susceptibility and inflammation-related pathways, including cytokine signaling, are increasingly recognized as key contributors to CRC pathogenesis. Interleukin-13 (IL-13) polymorphisms, particularly rs1800925 and rs20541, have been implicated in cancer biology; however, their roles in CRC remain inconclusive. MATERIALS AND METHODS:A hospital-based case-control study was conducted in Taiwan, including 362 CRC patients and 362 age- and sex-matched controls. Genomic DNA was extracted from peripheral blood, and IL-13 rs1800925 and rs20541 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. Associations between genotypes and CRC risk and clinicopathological features were estimated using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS:The genotype distributions of rs1800925 and rs20541 in controls conformed to the Hardy-Weinberg equilibrium (p=0.2098 and 0.7888, respectively). No overall significant associations were observed between IL-13 polymorphisms and CRC susceptibility. For rs1800925, the CT and TT genotypes showed ORs of 1.20 (95%CI=0.88-1.65, p=0.2772) and 1.42 (95%CI=0.80-2.54, p=0.2844), respectively. For rs20541, the AG and AA genotypes exhibited ORs of 1.11 (95%CI=0.82-1.51, p=0.5581) and 1.21 (95%CI=0.74-1.98, p=0.5185). However, rs1800925 CT+TT genotypes were associated with significantly increased risk of distant metastasis at diagnosis (OR=2.12, 95%CI=1.40-3.20, p=0.0005), while rs20541 AG+AA genotypes were associated with advanced stage (OR=1.50, 95%CI=1.03-2.19, p=0.0423) and metastatic disease at diagnosis (OR=2.16, 95%CI=1.39-3.36, p=0.0007). CONCLUSION:Although IL-13 rs1800925 and rs20541 polymorphisms are not associated with CRC susceptibility, they may be associated with clinicopathological aggressiveness at diagnosis, highlighting their potential utility in stratifying CRC severity, particularly in the Taiwanese population.

Epigenetic clocks are robust biomarkers of biological aging and have been associated with cancer susceptibility. However, the relationship between genetically predicted epigenetic age acceleration and head and neck cancer risk remains unclear. Using a large case-control study of 2189 head and neck squamous cell carcinoma (HNSCC) cases and 2189 age- and sex-matched controls, we investigated the associations between polygenic scores (PGSs) for multiple epigenetic clocks and HNSCC risk, and evaluated their potential causal roles using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNPs) associated with four epigenetic clocks (HannumAge, HorvathAge, GrimAge, and PhenoAge) were used to construct clock-specific PGSs. Logistic regression models were applied to assess associations between PGSs and HNSCC risk, while MR analyses, including inverse-variance weighted (IVW), weighted median, and MR-Egger methods, were used to infer potential causal relationships. Among the 48 epigenetic clock-associated SNPs, 12 showed nominal associations with HNSCC risk, and one variant (rs2275558 in PBX1) remained significant after Bonferroni correction (OR = 0.67, 95% CI: 0.60-0.76). PGSs for all four epigenetic clocks were higher in cases than in controls. In logistic regression analyses, each standard deviation increase in HannumAge PGS was associated with a 25% higher risk of HNSCC (OR = 1.25, 95% CI: 1.10-1.41), whereas HorvathAge, GrimAge, and PhenoAge PGSs showed weaker positive associations (ORs ranging from 1.06 to 1.10). Individuals in the highest PGS quartile for all four epigenetic clocks exhibiting 14%-25% higher risk than those in the lower three quartiles. MR analyses supported potential causal effects of genetically predicted HannumAge (IVW OR = 1.24 per SD increase, 95% CI: 1.09-1.42) and GrimAge (IVW OR = 1.23 per SD increase, 95% CI: 0.98-1.56) on HNSCC risk, with consistent estimates in weighted median analyses. Our results highlight biological aging as a potential etiologic mechanism for HNSCC and suggest that epigenetic clock-related genetic profiles may improve HNSCC risk stratification.

Asthma is a chronic inflammatory airway disease strongly influenced by genetic factors. Interleukin-33 (IL-33), a key mediator of type 2 immune responses, has been implicated in airway inflammation and remodeling. However, the effects of IL-33 polymorphisms on asthma susceptibility and severity remain unclear, particularly in East Asian populations. This study investigated five IL-33 polymorphisms (rs1891385, rs16924159, rs12551256, rs1929992, and rs7044343) in relation to asthma risk and severity in Taiwanese individuals. A total of 198 asthmatic patients and 453 age- and sex-matched controls were enrolled. Genotypes were determined using PCR-RFLP. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess associations with asthma susceptibility and severity. Among the five polymorphisms, only rs1929992 was significantly associated with asthma. Compared with the TT genotype, CT and CC carriers had reduced asthma risk (OR = 0.61 and 0.51, respectively). The dominant model (CT+CC) also showed a protective effect (OR = 0.58, 95%CI = 0.40–0.82, p = 0.0032), which was supported by allelic analysis (OR = 0.70, 95%CI = 0.55–0.89, p = 0.0044). Among the five polymorphisms, rs1929992 was associated with asthma susceptibility. Under the dominant model, CT + CC carriers showed lower odds of asthma than TT carriers (OR = 0.58, 95% CI = 0.40–0.82, p = 0.0032), and the association remained significant after correction for multiple testing. Exploratory stratified analyses identified associations in the younger and male subgroups, while exploratory severity analysis suggested lower odds of more severe asthma among variant genotype carriers. These secondary findings should be considered hypothesis-generating because of the reduced subgroup sample sizes. Overall, rs1929992 was associated with asthma susceptibility in this Taiwanese population; however, independent replication and functional studies are required before its biological or clinical relevance can be established.

Background: This study aimed to investigate the polymorphic genotypes of MDM2 rs937282, rs937283, rs2279744, and rs769412, as well as the combined effects of MDM2 genotypes and environmental factors on RCC susceptibility. Methods: A total of 135 RCC patients and 590 controls were recruited for MDM2 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative PCR was performed to assess MDM2 mRNA levels among 30 healthy individuals and 22 RCC patients. Results: MDM2 rs2279744, but not other polymorphisms, was significantly associated with an increased RCC risk (p = 0.0133). The MDM2 rs2279744 G allele was identified as a risk factor for RCC (odds ratio [OR] = 1.49, 95% confidence interval [CI] = 1.14-1.96, p = 0.0047). Among smokers (p = 0.0070), alcohol drinkers (p = 0.0233), individuals with hypertension (p = 0.0041), diabetes (p = 0.0225), and those with a family history of cancer (p = 0.0020), the MDM2 rs2279744 GT and GG genotypes exhibited increased RCC risks. However, this risk effect was not observed in non-smokers, non-drinkers, or individuals without hypertension, diabetes, or a family cancer history (all p > 0.05). Moreover, MDM2 mRNA levels were significantly higher in RCC patients compared to controls and varied among the rs2279744 genotypes, with GG genotype exhibiting the highest expression levels among both RCC patients and controls. Conclusions: This study highlights the association between MDM2 rs2279744 genotypes and RCC risk, suggesting that genotype-associated MDM2 mRNA levels could contribute to early RCC detection. Further studies are warranted to elucidate the detailed mechanisms underlying the role of MDM2 in RCC development.