由于白细胞介素 (IL)-10 基因中单核苷酸多态性 (SNP) 的存在仍然是开发消化道癌症有效疗法的主要挑战，因此进行了这项病例对照研究，以评估基因型、位于IL-10基因启动子区的两个SNP（-1082A/G（rs1800896）和-592A/C（rs1800872））的单倍型和双倍型对突尼斯人结直肠癌（CRC）的发病率、严重程度和预后的影响。IL采用PCR-SSP对130例CRC病例和165例健康受试者（HS）中的-10基因SNP进行分析。对于IL-10 -1082A/G SNP，病例组和HS组之间基因型频率的比较显示G等位基因显着降低隐性模型下的 CRC 风险（GG 与 AA AG：OR [95% CI] = 0.44 [0.21-0.93]，p = 0.03）。相反，在共显性模型（AG 与 AA GG）和高易感性之间观察到正相关（OR [95%CI] = 1.65 [1.02-2.63]，p = 0.04）。按疾病部位分层后，还发现隐性模型可降低对结肠癌的易感性（OR [95%CI] = 0.18 [0.04-0.72]，p = 0 0.01），而纯合子模型（AA 与 GG）则降低了对结肠癌的易感性。建议作为风险因素（OR [95%CI] = 5.16 [1.31-23.26]，p = 0.02）。此外，共显性模型（AG 与 AA GG）使直肠癌的风险加倍（OR [95%CI] = 1.98 [1.07-3.70]，p = 0.03）。对于 IL-10 -592A/C SNP，共显性模型（AC 与 AA CC）对 CRC 的发展具有保护作用（OR [95% CI] = 0.59 [0.36-0.94]，p = 0.03）。 IL-10 基因单倍型与 CRC 风险无关。按疾病部位进行的分层分析表明，Hap3（-1082G 和 -592C 等位基因）的存在特异性降低了患结肠癌的风险（OR [95%CI] = 0.51 [0.32-0.80]，p = 0.003）。此外，纯合 Hap3/Hap3 双倍型显着降低了对 CRC 的易感性（OR [95%CI] = 0.35 [0.14-0.85]，p = 0.02）。有趣的是，这种双倍型尚未在结肠癌患者中被发现。 Kaplan-Meier 分析表明，纯合 Hap2/Hap2 双倍型与总生存率下降显着相关（对数秩：p = 0.01）。在结肠癌亚组中也观察到了这种关联（对数排序：p = 0.001）。我们的研究结果初步表明，IL-10 基因内的 -1082A/G 和 -592/AC SNP 可能与发病机制表现出显着关联和 CRC 的预后结果。然而，仍需要进一步调查来验证和确定我们调查结果的准确性。© 2024 作者。

As the presence of single nucleotide polymorphisms (SNPs) in the interleukin (IL)-10 gene continues to be a major challenge in the development of effective therapies for digestive cancers, this case-control study was conducted to assess the possible influence of genotype, haplotype and diplotype for two SNPs (-1082A/G (rs1800896) and -592A/C (rs1800872)) located in the promoter region of IL-10 gene on the incidence, severity and prognosis of colorectal cancer (CRC) in Tunisians.IL-10 gene SNPs were analyzed in 130 CRC cases and 165 healthy subjects (HS) using PCR-SSP.For the IL-10 -1082A/G SNP, the comparison of genotype frequencies between cases and HS groups showed that the G allele significantly reduced CRC risk under the recessive model (GG vs. AA + AG: OR [95%CI] = 0.44 [0.21-0.93], p = 0.03). Conversely, a positive association was observed between the codominant model (AG vs. AA + GG) and high susceptibility (OR [95%CI] = 1.65 [1.02-2.63], p = 0.04). After stratification by disease site, the recessive model was also found to reduce susceptibility to colon cancer (OR [95%CI] = 0.18 [0.04-0.72], p = 0 0.01), while the homozygote model (AA vs. GG) was suggested as a risk factor (OR [95%CI] = 5.16 [1.31-23.26], p = 0.02). Furthermore, the codominant model (AG vs. AA + GG) doubled the risk of rectum cancer (OR [95%CI] = 1.98 [1.07-3.70], p = 0.03). For the IL-10 -592A/C SNP, the codominant model (AC vs. AA + CC) has a protective effect against the development of CRC (OR [95%CI] = 0.59 [0.36-0.94], p = 0.03). The IL-10 gene haplotype was not associated with CRC risk. A stratified analysis by disease site demonstrated that the presence of Hap3 (-1082G and -592C alleles) specifically reduced the risk of developing colon cancer (OR [95%CI] = 0.51 [0.32-0.80], p = 0.003). Moreover, homozygous Hap3/Hap3 diplotype significantly reduced susceptibility to CRC (OR [95%CI] = 0.35 [0.14-0.85], p = 0.02). Interestingly, this diplotype has not been identified in colon cancer patients. Kaplan-Meier analysis showed that the homozygous Hap2/Hap2 diplotype was significantly associated with decreased overall survival (Log-rank: p = 0.01). This association was also observed in the colon cancer subgroup (Log-rank: p = 0.001).Our findings provide preliminary indications that the -1082A/G and -592/AC SNPs within the IL-10 gene may exhibit significant associations with the pathogenesis and prognostic outcomes of CRC. However, further investigations are still warranted to validate and establish the veracity of our findings.© 2024 The Authors.