Preliminary findings suggest a possible association between IL1B rs1143634 T allele carriage and cutaneous melanoma susceptibility in this cohort, and the Stage IV and upper-limb observations should be considered hypothesis-generating.
Abstract
Background: Immune modulation is central to cutaneous melanoma, and antitumor immune responses may be influenced by host genetic background. This study investigated the association between the interleukin-1β gene (IL1B) exon 5 synonymous single-nucleotide polymorphism rs1143634 (+3954 C>T) and cutaneous melanoma in a Northeast Italian case–control cohort. Methods: The study included 133 Caucasian patients with cutaneous melanoma and 945 healthy controls from Northeast Italy. The rs1143634 polymorphism was genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). Results: Compared with healthy controls, melanoma patients showed higher frequencies of the rs1143634 T allele [27.8% vs. 20.3%; odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.13–2.03, p = 0.005] and CT genotype (43.6% vs. 31.6%; OR = 1.67, CI = 1.16–2.42, p = 0.006), whereas the CC genotype was less frequent (50.4% vs. 63.9%; OR = 0.57, CI = 0.40–0.83, p = 0.003). TT + CT genotypes were more frequent among non-metastatic melanoma cases than controls (OR = 2.23, CI = 1.37–3.64, p = 0.001), but the direct comparison between metastatic and non-metastatic cases was not statistically significant. Among melanoma patients, TT + CT carriers showed an inverse association with Stage IV disease (OR = 0.38, CI = 0.15–0.94, p = 0.036) and a positive association with upper-limb melanoma (OR = 9.10, CI = 1.11–75.0, p = 0.040); these subgroup findings were exploratory because of small numbers and wide confidence intervals. Conclusions: These preliminary findings suggest a possible association between IL1B rs1143634 T allele carriage and cutaneous melanoma susceptibility in this cohort. The Stage IV and upper-limb observations should be considered hypothesis-generating. Larger independent studies, correction-aware statistical designs, cytokine or expression measurements, and functional validation are needed to confirm these observations and clarify their biological relevance.
Background: Hypoxia and oxidative stress are central features of cutaneous melanoma biology. Body mass index (BMI) and smoking, both of which can influence systemic hypoxia, inflammation, and oxidative stress, have shown inconsistent associations with melanoma. We investigated the association of the hypoxia-inducible factor-1 alpha gene (HIF1A) rs11549465 (1772 C>T; Pro582Ser) polymorphism, alone and in combination with overweight/obesity or smoking habits, with cutaneous melanoma susceptibility and clinicopathological characteristics. Methods: This observational case–control study included 132 Caucasian Italian patients with cutaneous melanoma and 312 healthy controls. The rs11549465 polymorphism was genotyped by genomic DNA restriction fragment analysis. Logistic regression provided age- and sex-adjusted and mutually adjusted estimates. Results: Genotype and allele frequencies did not differ between patients and controls. Within the melanoma cohort, smoking for ≥20 years remained associated with metastatic disease after adjustment for BMI ≥ 25 kg/m2, age at diagnosis, and sex (aOR = 3.12, p = 0.006), whereas BMI did not (aOR = 1.23, p = 0.612). Compared with healthy controls, metastatic melanoma was independently associated with BMI ≥ 25 kg/m2 (aOR = 2.26, p = 0.010) and smoking for ≥20 years (aOR = 3.85, p < 0.001). Mean pack-years were higher in melanoma patients than controls (9.4 ± 16.7 vs. 5.1 ± 12.2; p = 0.002), and ≥10 and ≥20 pack-years remained associated after age- and sex-adjustment (aOR = 2.19, p = 0.001 and aOR = 3.31, p < 0.001, respectively). Mean pack-years were higher in MetM than NMetM (13.1 ± 21.0 vs. 5.9 ± 10.0; p = 0.013), and ≥20 pack-years was associated with MetM (OR = 3.05, p = 0.017). Adjusted associations with head/neck melanoma (n = 13) were observed for CC plus BMI ≥ 30 kg/m2 (aOR = 9.07, p < 0.001), ≥20 cigarette/day (aOR = 5.96, p = 0.004), ≥20 years smoking (aOR = 6.64, p = 0.003), and other smoking measures. Conclusions: To our knowledge, this is the first report on the interplay between the rs11549465 polymorphism and cutaneous melanoma. HIF1A rs11549465 was not independently associated with melanoma susceptibility. Associations involving smoking, BMI, joint genotype–lifestyle exposures, and anatomical localization had wide confidence intervals and were exploratory; small subgroups and multiple comparisons require cautious interpretation and independent validation.
The GA genotype of rs5742621 was significantly associated with elevated IGF-1 levels and increased PCa risk, promoting cell proliferation, inhibiting apoptosis, and accelerating tumor growth.
Fatima Abdul Jabbar, R. AlChalabi, Russul AlObaidi et al.· Iraqi Journal of Science· 0 citations
Background: Granulomatosis with polyangiitis (GPA) is an autoimmune disorder that results from an interplay of genetic factors and environmental influences. We investigated the association between two polymorphisms in the VEGF gene, specifically rs2010963 and rs833061, and the likelihood of developing GPA. Methods: A case-control study involving 224 participants was conducted, comprising 104 individuals diagnosed with GPA and 120 control subjects. The high-resolution melting (HRM) technique was employed for genotyping these polymorphisms. Results: The findings revealed a significant difference in the distribution of the CC genotype and C allele for rs2010963 between the control and case groups (CC vs GG; OR: 2.687; 95% CI [1.185-6.264], P: 0.014; C vs G; OR: 1.628; 95% CI [1.097-2.421], P: 0.012). Moreover, patients with the GC + CC genotype exhibited elevated mean levels of creatinine, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), as well as a higher incidence of alveolar hemorrhage compared to those with the GG genotype. Concerning rs833061, no association with GPA risk was identified; however, correlations were noted with certain laboratory and clinical parameters, including PR3-ANCA levels, septal perforation, alveolar hemorrhage, renal involvement, and rapidly progressive glomerulonephritis (RPGN). Conclusion: The C allele of rs2010963 is linked to an increased risk of developing GPA and certain laboratory and clinical parameters, while the rs833061 polymorphism does not appear to be associated with GPA risk but is correlated with various laboratory and clinical indices.
Amirali Pourebrahimi, Mozhdeh Saghaei, Naeim Ehtesham et al.· Caspian Journal of Internal...· 0 citations
Tuberculosis (TB) remains a major infectious disease burden, and inter-individual heterogeneity in progression from exposure to active disease suggests contributions from host genetic factors. SLC11A1 (formerly NRAMP1) encodes a phagosomal divalent cation transporter implicated in macrophage-mediated antimicrobial defense; the non-synonymous rs17235409 polymorphism (D543N) has been evaluated in multiple populations with inconsistent results. We conducted a retrospective matched case–control study in Qiandongnan, Guizhou Province, China, including 50 patients diagnosed with TB (2022–2023) and 50 healthy controls frequency-matched by ethnicity and selected demographics. Participants were drawn from Miao, Dong, and other minority groups. Among TB cases, the frequencies of the GG, GA, and AA genotypes were 80.0%, 20.0%, and 0%, respectively, compared with 74.0%, 18.0%, and 8.0% among controls. The overall genotype distribution did not differ significantly between the 2 groups (P = .124). Under the dominant model, no significant association was observed between rs17235409 and TB susceptibility (OR = 0.71, 95% CI: 0.28–1.82; P = .635). Allelic analysis showed that the frequency of the A allele was lower in cases than in controls (10.0% vs 17.0%), but this difference was not statistically significant (OR = 0.54, 95% CI: 0.24–1.25; P = .214). Ethnicity-stratified analyses similarly showed no statistically detectable associations in Miao, Dong, or other groups. The minor allele frequency was 0.095, lower than the Han Chinese reference from 1000 Genomes. In this pilot study of multi-ethnic populations from southwestern China, no statistically significant association was identified between the SLC11A1 rs17235409 polymorphism and tuberculosis susceptibility. Although the A allele appeared less frequent among cases, the limited sample size and statistical power preclude definitive conclusions regarding modest or ethnic-specific effects. These findings provide preliminary genetic data from underrepresented ethnic minority populations and warrant validation in larger multicenter studies.
Breast cancer (BC) is one of the most common and deadly cancers affecting women worldwide. This study is aimed at investigating the association between BC risk and two single nucleotide polymorphisms (SNPs): ESR1 (rs2234693) and PIK3CA (rs6443624) in a Bangladeshi population. A case‐control study was conducted with 112 BC patients and 124 healthy controls (HCs). Genomic DNA was extracted from peripheral blood samples, and genotyping was performed using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Genotype and allele frequencies were analyzed to assess their association with BC risk. Genotype distributions for both ESR1 and PIK3CA conformed to Hardy–Weinberg equilibrium. The CT genotype of ESR1 was associated with a reduced risk of BC, whereas the CA genotype of PIK3CA was linked to an increased risk. The dominant model for ESR1 (CT + TT vs. CC) demonstrated a significant protective effect (aOR = 0.288, 95% CI: 0.160–0.516), whereas the dominant model for PIK3CA (CA + CC vs. AA) showed a higher risk (aOR = 4.166, 95% CI: 2.363–7.347). Over‐dominant models supported these findings, while recessive models for both SNPs showed no significant associations. The findings suggest that ESR1 (rs2234693) may have a protective role and PIK3CA (rs6443624) may increase susceptibility to BC in Bangladeshi women. These SNPs may provide preliminary evidence for potential use as genetic susceptibility markers, but larger multicenter studies are needed before any clinical application can be considered.
M. H. Chowdhury, Faria Billal Shaolin, Nishat Tabassum Khusbu et al.· Human Mutation· 0 citations
