Association of SMAD7 genetic markers and haplotypes with colorectal cancer risk

Purpose Colorectal cancer (CRC) is one of the common cancers with a high mortality rate worldwide. In Iran, there has been a trend of increased incidence of colorectal cancer in the last three decades that necessitates the early diagnosis. Genetic factors have an influential role in its etiology along with the conventional risk factors such as age, diet, and lifestyle. Results from GWAS have shown significant associations between SMAD7 gene variants and risk of CRC. This study aimed to assess the association of certain polymorphisms as well as haplotypes of this gene and risk of colorectal cancer. Methods and materials This study was designed as a case–control association study. After obtaining ethical approval and informed consent, blood samples from 209 patients with colorectal cancer were collected and DNA was extracted. Four variants: rs4939827, rs34007497, rs8085824 and rs8088297 were genotyped using ARMS-PCR method. Results SMAD7 rs4939827 in the recessive and co-dominant models was associated with colorectal cancer risk [TT/CT + CC: OR = 2.90, 95%CI (1.38–6.09), p = 0.005; CC + TT/CT: OR = 1.66, 95%CI (1.00–2.75), p = 0.01]. Haplotype analysis indicated that some SNP combinations including two for-SNPs haplotypes of T-T-C-C and T-C-C-A were significantly associated with CRC risk. Conclusion Based on the identified association of SMAD7 gene variations and haplotypes with colorectal cancer risk in our population, genetic variations in this gene region may have a role in CRC development. This data may shed light on the genetic predisposition of CRC which involves different pathways including TGF-β.

Cytokine Gene Polymorphism and Cancer Risk: A Promising Tool for Individual Susceptibility and Prognostic Implications

Cytokines are potent molecules produced mainly by specific activated immune cells to control inflammatory responses besides other biologic processes. Although active participation of cytokines provides defense against carcinogenesis on the other hand, deregulation at the genetic level influences their activity to promote tumor development. Among many aspects, constitutional polymorphic sequence variations are key factors that derange the cytokine expression to lead an individual’s propensity to risk for different cancers. Cytokine polymorphisms are now believed to alter these critical molecules that have a dual face in carcinogenesis as, when implicated in the activation of the immune response, these molecules check the cancer development while their persistent inflammatory reaction can envisage the development of malignancy and tumor growth. We have given ample evidence of case-control studies in a range of cancers where substantial evidence, as reported in this chapter, links polymorphism of cytokine gene susceptibility with numerous cancers. Cytokine gene polymorphism is vital to be significant bimolecular genetic determinants of susceptibility and prognosis of cancer. A strong need is felt for more case-control association studies in cytokine candidate genes involved in specific pathways for particular cancer in bigger powered sample sizes involving additional variables to disclose their factual risk for cancer.

Taking JEMCA to the world stage

2021 is a landmark year for the Journal of the European Mosquito Control Association (JEMCA)! In the last 12 months we moved from self-publishing to the professional publisher Wageningen Academic Publishers (WAP). This is intended to gain efficiency in the submission, reviewing and publishing process, and also to get better indexed and evaluated, the final aim being to link authors and readers, promoting dissemination of science, improving knowledge on vectors and addressing related challenges.

Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function

<strong>OBJECTIVE:</strong> To evaluate the association between <i>PCSK9 </i>predicted loss-of-function variants (pLoF) and glycemic traits, hepatobiliary function and neurocognitive traits. <p><strong>RESEARCH DESIGN AND METHODS:</strong> We identified carriers of <i>PCSK9</i> pLoF in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid/lipoprotein traits, which served as a positive control. Association of <i>PCSK9 </i>pLoF carrier status and glycemic traits, hepatobiliary function, neurocognitive traits was then evaluated as a measure for adverse effects. </p> <p><strong>RESULTS:</strong> We identified 374 individuals with 41 pLoF variants. As expected, we found that <i>PCSK9</i> pLoF carriers had significantly lower LDL-C (<i>P</i> = 7.4 × 10^-55) and apoB levels (<i>P</i> = 7.6 × 10^-50) compared with noncarriers. However, we found no significant associations between pLoF carrier-status and glycemic traits, hepatobiliary function and neurocognitive traits (<i>P</i> > 0.05).</p> <p><strong>CONCLUSIONS</strong>: Our results do not support adverse effects of <i>PCSK9 </i>pLoF on glycemic traits, hepatobiliary function or neurocognitive traits.</p>

Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function

<strong>OBJECTIVE:</strong> To evaluate the association between <i>PCSK9 </i>predicted loss-of-function variants (pLoF) and glycemic traits, hepatobiliary function and neurocognitive traits. <p><strong>RESEARCH DESIGN AND METHODS:</strong> We identified carriers of <i>PCSK9</i> pLoF in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid/lipoprotein traits, which served as a positive control. Association of <i>PCSK9 </i>pLoF carrier status and glycemic traits, hepatobiliary function, neurocognitive traits was then evaluated as a measure for adverse effects. </p> <p><strong>RESULTS:</strong> We identified 374 individuals with 41 pLoF variants. As expected, we found that <i>PCSK9</i> pLoF carriers had significantly lower LDL-C (<i>P</i> = 7.4 × 10^-55) and apoB levels (<i>P</i> = 7.6 × 10^-50) compared with noncarriers. However, we found no significant associations between pLoF carrier-status and glycemic traits, hepatobiliary function and neurocognitive traits (<i>P</i> > 0.05).</p> <p><strong>CONCLUSIONS</strong>: Our results do not support adverse effects of <i>PCSK9 </i>pLoF on glycemic traits, hepatobiliary function or neurocognitive traits.</p>

Association between Maternal Non-Coding Interferon-λ Polymorphisms and Congenital Zika Syndrome in a Cohort from Brazilian Northeast

Congenital Zika syndrome (CZS) is characterized by a diverse group of congenital malformations induced by ZIKV infection during pregnancy. Type III interferons have been associated with placental immunity against ZIKV and restriction of vertical transmission in mice, and non-coding single-nucleotide polymorphisms (SNPs) on these genes are well known to influence susceptibility to other viral infections. However, their effect on ZIKV pathogenesis has not yet been explored. To investigate whether maternal non-coding SNPs at IFNL genes are associated with CZS, 52 women infected with ZIKV during pregnancy were enrolled in a case–control association study. A total of 28 women were classified as cases and 24 as controls based on the presence or absence of CZS in their infants, and seven Interferon-λ non-coding SNPs (rs12980275, rs8099917, rs4803217, rs4803219, rs8119886, rs368234815, rs12979860) were genotyped. The results of logistic regression analyses show an association between the G allele at rs8099917 and increased susceptibility to CZS under a log-additive model (adjustedOR = 2.80; 95%CI = 1.14–6.91; p = 0.02), after adjustment for trimester of infection and genetic ancestry. These results provide evidence of an association between Interferon-λ SNPs and CZS, suggesting rs8099917 as a promising candidate for further studies on larger cohorts.