Interleukin-1β Gene (IL-1B) rs16944 (-511 C > T) Promoter Polymorphism Is Associated with Cutaneous Melanoma Susceptibility, Stage, and Anatomical Localization in a Northern Italian Case–Control Study
Jul 2026· Current Oncology· Vol 33, pp. 436· 1 citation· 80 references
Medicine
TL;DR
The genotype and allele frequencies of the interleukin-1β gene (IL-1B) promoter polymorphism rs16944 (-511, C > T) in cutaneous melanoma patients and healthy controls from Northeastern Italy revealed a possible candidate marker associated with melanoma susceptibility, Stage IV status, and lower-extremity localization.
Abstract
Simple Summary We determined the genotype and allele frequencies of the interleukin-1β gene (IL-1B) promoter polymorphism rs16944 (-511, C > T) in cutaneous melanoma patients and healthy controls from Northeastern Italy, a region with a high incidence of melanoma. The CC genotype and C allele were more frequent in melanoma cases than in healthy controls. Among melanoma patients, the CC genotype was more frequent in Stage I disease and in melanomas with Breslow thickness ≤ 0.75 mm, but less frequent in Stage IV melanoma. The CT genotype was associated with approximately 3-fold higher odds of Stage IV disease and approximately 2- to 3-fold higher odds of lower-limb or lower-extremity melanoma, including after multivariable adjustment. Thus, rs16944 emerged as a possible candidate marker associated with melanoma susceptibility, Stage IV status, and lower-extremity localization. Independent studies are required to confirm these preliminary, exploratory findings.
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
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
Chemokine (CK) and chemokine receptors (CKR) regulate cell growth, tumor immunity, migration, angiogenesis, and metastasis. We evaluated associations of inherited CK/CKR variants with subsequent primary melanomas among patients with a previous melanoma. Our population-based cohort included 2,458 incident single primary and 1,205 multiple primary melanoma (MPM) cases. We examined 215 a priori candidate polymorphisms selected based on prior evidence and predicted functional relevance, along with nine haplotype blocks. Logistic regression estimated odds ratios and 95% confidence intervals, adjusting for age at diagnosis, sex, age by sex interaction, and study center. Thirty variants across fourteen genes were nominally associated with MPM (p<0.05), with effect sizes ranging from 16% to 80%. Five haplotypes in CXCL12, CCL18, CXCR2, and CCR9 were significantly associated with MPM (pglobal<0.03) with stronger effects than individual effect-alleles. Functional annotation identified 160 associated index variants and linkage disequilibrium (LD) proxies acting as skin expression Quantitative Trait Loci (eQTLs) for CXCR2, XCR1, BCL9L, FYCO1, PNKD, RUFY4, and RP11–378A13.1 (p-value <1.06E-05 to 4.3E-34). These variants were classified functionally as candidate causal variants based on convergent regulatory annotation and skin-specific eQTL evidence, linking CK/CKR variants and haplotypes to downstream genes involved in epithelial–mesenchymal–like transition, matrix remodeling, and other tumorigenic processes, thereby implicating immune regulatory mechanisms in melanoma development. To our knowledge, this is the first study to demonstrate an association of a priori CK/CKR variants with subsequent melanoma risk. Validation and evaluation of associations with tumor characteristics and survival are warranted.
I. Orlow, L. Luo, Isidora Autuori et al.· Melanoma research· 0 citations
BACKGROUND
The specific effect of the LINC00673 rs9914618 single nucleotide polymorphism (SNP) on lung squamous cell carcinoma (LUSC) remains unclear. This study aims to evaluate its association with LUSC susceptibility and prognosis.
MATERIALS AND METHODS
We recruited 305 LUSC patients and 336 healthy controls. LINC00673 expression was measured by qRT-PCR. The rs9914618 genotype was determined using TaqMan assays. Disease-free survival was estimated by Kaplan-Meier analysis. Multivariate Cox regression yielded hazard ratios with 95% confidence intervals.
RESULTS
LINC00673 expression was significantly upregulated in LUSC tissues and serum relative to the control group. The A allele at rs9914618 was positively associated with increased LINC00673 transcription. Carriers of the A allele or AA genotype had a higher risk of LUSC. Patients with GA or AA genotypes showed more severe clinicopathological features and lower five‑year survival rates. The rs9914618 polymorphism was validated as an independent prognostic factor.
CONCLUSION
The LINC00673 rs9914618 polymorphism may serve as a potential prognostic factor for LUSC, showing significant associations with patient outcomes and risk stratification.
Xing-Shu Zhang, Fen Wang, Licai Zhang et al.· Expert Review of Molecular D...· 0 citations
Background Alcohol dependence and cirrhosis are key outcomes of increased alcohol use, with genetic factors increasingly implicated. A functional promoter variant (rs361525) in the TNF-α gene may contribute to ALD pathogenesis, while a loss-of-function variant (rs58542926) in TM6SF2 modifies liver disease progression. We aimed to study these SNPs and assess DNA methylation at TM6SF2 loci in individuals with and without alcohol-related cirrhosis. Methods The study included men (N = 243) with alcohol dependence with cirrhosis (AUD-C+ve) and without cirrhosis (AUD-C-ve), based on ICD-10 criteria, recruited from SJMCH. Fibroscan and/or sonography (LSM < 14 kPa) ruled out severe fibrosis. Genotyping was performed for TNFα (rs361525) and TM6SF2 (rs58542926). Genomic DNA (N = 100) underwent bisulfite conversion followed by pyrosequencing at TM6SF2 loci. Methylation levels were calculated separately for individual CpG sites and as the mean of four CpG sites. Group differences were assessed using unpaired t-tests, and genetic models were applied based on risk allele status. Results Genotype and allele frequencies at both loci were comparable between AUD-C+ve and AUD-C–ve groups. TM6SF2 methylation was significantly reduced in the AUD-C+ve group (uncorrected p = 0.03). A trend was also noted for TNF-genotype with A-carriers having lower TM6SF2 global methylation levels (p = 0.06). We did not observe any differences in genotype and allele frequencies for both TM6SF2 and TNFα variants. Duration of alcohol consumption was significantly associated with TM6SF2 methylation (p = 0.02). Conclusion TM6SF2 hypomethylation in AUD-C+ve individuals may influence lipid metabolism and contribute to liver injury and HCC progression. Reduced methylation among TNF-α risk allele carriers suggests a potential gene–epigenetic interaction. Overall, higher alcohol exposure and genetic susceptibility may together predispose to worsening alcohol-related cirrhosis.
B. Shankarappa, J. Mahadevan, Pratima Murthy et al.· Frontiers in Medicine· 0 citations
