A Meta-Analysis for Association of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629, and TLR9 rs352140 Polymorphisms with Susceptibility to Cervical Carcinoma.

BACKGROUND: In spite of substantial declines in both incidence and mortality rates in the past 50 years, cervical cancer remains one of the leading causes of cancer associated mortality among women globally. We performed this meta-analysis to explore the role of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629 and TLR9 rs352140 polymorphism with susceptibility to cervical carcinoma. METHODS: The search databases include PubMed, SciELO, MedRxiv, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, and China Biology Medicine disc up to 30 June 2021. The language is limited to English and Chinese. The comparison between the polymorphisms and cervical cancer was assessed using pooled odds ratio (OR) and 95% confidence interval (CI). The data are statistically analyzed by Comprehensive Meta-Analysis (CMA) 2.0 software. RESULTS: A total of 59 studies including seven studies with 1,112 cases and 1,233 controls on XRCC3 rs861539, 14 studies with 2,694 cases and 3349 controls MTHFR rs1801133, four studies with 1,121 cases and 1,109 controls on IL-12B rs3212227, seven studies with 1,452 cases and 2,186 controls on IL-6 rs1800795, 20 studies with 4,781 cases and 4909 controls on TNF-α rs1800629, and seven studies with 1743 cases and 2292 controls on TLR9 rs352140 were included. There was a significant association between XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 polymorphisms and an increased risk of cervical carcinoma in overall population. However, the MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms were not associated. CONCLUSION: The pooled analysis showed that XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 were associated with cervical carcinoma susceptibility, but not MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms.

Association of IL-6 -174G>C and -572G>C Polymorphisms with Susceptibility to Cervical Cancer and Ovarian Cancer.

BACKGROUND: During the past decades, the expansion of molecular development has had a key role in understanding the basis of gynecological cancer. Interleukin-6 (IL-6) is known to be involved in the pathogenesis of different cancers. Here, we evaluated the association of IL-6 -174G>C and -572 G>C polymorphisms with susceptibility to cervical and ovarian cancers in an Iranian population. METHODS: A total of 131 cases with ovarian cancer, 124 cases with cervical cancer and 140 healthy subjects were enrolled to the study. DNA was extracted from peripheral blood cells of subjects to genotype the IL-6 -174G>C and -572 G>C polymorphisms by amplification refractory mutation system (RFLP) polymerase chain reaction (PCR). RESULTS: There was a significant association of IL-6 -174G>C CC genotype (OR= 3.231, 95% CI: 1.130-9.239, p=0.029) and C allele (OR = 1.915; 95%CI: 1.266-2.896, p=0.002) with an increased risk of ovarian cancer. Moreover, the IL-6 -174G>C CC genotype (OR= 3.162, 95% CI: 1.094-9.141, p=0.034) and C allele (OR = 1.724; 95%CI: 1.129-2.633, p=0.012) was associated with increased risk of cervical cancer. CONCLUSIONS: This study showed that the IL-6 -174G>C polymorphism was associated with ovarian cancer and cervical cancer risk. However, IL-6 -572 G>C polymorphism was not associated.

A meta-analysis for association of eNOS VNTR 4b/a, - 786 T > C and + 894G > T polymorphisms with risk of recurrent pregnancy loss.

BACKGROUND: The association of polymorphisms at nitric oxide synthases (eNOS) gene with recurrent pregnancy loss (RPL) susceptibility has been the focus of attention in several studies. However, the conclusions have been divergent and controversial. Therefore, we performed this study to precisely evaluate the association of eNOS polymorphisms with the risk of RPL. METHODS: A universal search in PubMed, Web of Knowledge, SciELO, MedRxiv, Scopus and web of Science was performed to identify relevant studies up to January 25, 2020. RESULTS: A total of 39 eligible studies including 15 studies with 2274 cases and 1933 controls on VNTR 4b/a, nine studies with 1640 cases and 1268 controls on -786C > T, and 15 studies with 2660 cases and 2557 controls on + 894G > T polymorphism were selected. Pooled data revealed that eNOS VNTR 4b/a (dominant model: OR = 1.174, 95% CI 1.021-1.350, p = 0.025) and + 894G > T (allele model: OR = 1.278, 95% CI 1.024-1.595, p = 0.030; homozygote model: OR = 1.442, 95% CI 1.084-1.917, p = 0.012; dominant model: OR = 1.305, 95% CI 1.006-1.693, p = 0.045; and recessive model: OR = 1.378, 95% CI 1.045-1.817, p = 0.023) polymorphisms were significantly associated with an increased risk of RPL, but not - 786 T > C. Stratified analysis by ethnicity revealed that the eNOS + 894G > T was associated with RPL risk in Asians. CONCLUSIONS: To sum up, our results indicated that the eNOS VNTR 4b/a and + 894G > T polymorphisms might be contributing to RPL development, but not the - 786C > T polymorphism.

Association of GRIA1 polymorphisms with ovarian response to human menopausal gonadotropin in Iranian women.

OBJECTIVE: Glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) is a subunit of a ligand-gated ion channel that regulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by controlling the release of gonadotropin-releasing hormone. Few studies have investigated the association between the GRIA1 gene and human infertility. This study evaluated the association of the GRIA1 rs548294 C > T and rs2195450 G > A polymorphisms with the ovarian response to human menopausal gonadotropin (HMG) in Iranian women. METHODS: One hundred women with histories of at least 1 year of infertility were included. On the second day of menstruation, patients were injected with HMG; on the third day, blood samples were collected. After hormonal analysis, the GRIA1 rs548294 C > T and rs2195450 G > A genotypes of samples were identified via the restriction fragment length polymorphism method, and on day 9, the number of follicles was assessed via ultrasound. RESULTS: For the GRIA1 rs548294 C > T and rs2195450 G > A single nucleotide polymorphisms, the subjects with CT and GG genotypes, respectively, displayed the highest mean FSH level, LH level, and number of follicles on day 9 of the menstrual cycle (p< 0.05). Significant positive correlations were observed between LH and FSH (p< 0.01), LH and follicle count (p< 0.01), FSH and age (p< 0.05), follicle count and age (p= 0.048), and FSH and follicle count (p< 0.01). CONCLUSION: This study showed a significant relationship between GRIA1 polymorphisms and ovarian response to the induction of ovulation. Therefore, determining patients' GRIA1 genotype may be useful for improving treatment and prescribing suitable doses of ovulation-stimulating drugs.