Polymorphisms in genes related to inflammation and obesity and colorectal adenoma risk

Abstract

We previously investigated the association between single nucleotide polymorphisms (SNPs) in genes related to obesity and inflammation and colorectal cancer in the CLUE II cohort. However, the relationships between these SNPs and colorectal adenomas have not been well evaluated. In a nested case-control study of 135 incident adenoma cases and 269 matched controls in the CLUE II cohort (1989-2000), we genotyped 17 candidate SNPs in 12 genes (PPARG, TCF7L2, ADIPOQ, LEP, IL10, CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and 19 tagSNPs in three genes (IL10, CRP, and TLR4). Conditional logistic regression was used to calculate odds ratios (OR) for adenomas (overall and by size, histology, location, number). Polymorphisms in the inflammatory-related genes CRP, ADIPOQ, IL6, and TLR4 were observed to be associated with adenoma risk. At rs1205 in CRP, T (minor allele) carriers had a higher risk (OR 1.67, 95%CI 1.07-2.60; reference: CC) of adenomas overall and adenomas with aggressive characteristics. At rs1201299 in ADIPOQ, the AC genotype had a higher risk (OR 1.58, 95%CI 1.00-2.49) of adenomas, while the minor AA genotype had a borderline inverse association (OR 0.44, 95%CI 0.18-1.08; reference: CC). At rs1800797 in IL6, the AA genotype had a borderline inverse association (OR 0.53, 95%CI 0.27-1.05; reference: GG). Three TLR4 tagSNPs (rs10116253, rs1927911, rs7873784) were associated with adenomas among obese participants. None of these SNPs were associated with colorectal cancer in our prior study in CLUE II, possibly suggesting a different genetic etiology for early colorectal neoplasia.

Statistical meta-analysis to investigate the association between the Interleukin-6 (IL-6) gene polymorphisms and cancer risk

“…Some GWA studies have also reported that some polymorphisms of the IL-6 gene are insignificantly associated with blood cancer [ 13 – 25 ] and significantly associated with breast cancer [ 26 – 36 ] whereas some other studies [ 37 – 40 ] reported no association with breast cancer. Similarly, for cervical and colon cancer development, some studies reported a significant association [ 41 – 46 and 49 – 56 respectively] whereas other studies reported no significant association [ 44 , 47 , 48 , 57 – 61 respectively]. The same scenario persists for liver cancer: associated [ 62 – 68 ] and not “associated [ 69 – 71 ]; lung cancer: associated [ 72 – 77 ] and not associated [ 78 – 83 ]; prostate cancer: associated [ 11 , 84 – 91 ] and not associated [ 92 – 98 ]; stomach cancer: claimed a significant association [ 106 – 112 ] and some other studies claimed insignificant association [ 111 , 113 – 115 ].…”

Association of C‐reactive protein (CRP) rs1205 and rs2808630 variants and risk of cancer

“…In that article, only five case–control studies were summarized. Since then, several new case‐control studies were published (Huang et al, 2018; Markt et al, 2014; Nimptsch et al, 2015; Zhang et al, 2015; Zhou & Bai, 2019). We pooled them together and observed that the CRP rs2808630 T>C polymorphism are also associated with risk of cancer in Asians.…”

“…However, due to the relatively small sample size, it is most likely to lead to significant differences in the results. The purpose of the present analysis was to comprehensively investigate the correlation between the two CRP variants and susceptibility of cancer (Chaturvedi et al, 2010; Chen, Liu, Zhao, & Zang, 2019; Gong et al, 2013; Huang et al, 2018; Markt et al, 2014; Minamiya et al, 2010; Motoyama et al, 2009; Nimptsch et al, 2015; Ognjanovic et al, 2010; Pierce et al, 2009; Poole et al, 2009; Siemes et al, 2006; Slattery et al, 2011; Tsilidis et al, 2009; Xu et al, 2013; Yang, Huang, Chang, & Lin, 2011; Zhang et al, 2015; Zhou & Bai, 2019).…”

The Role of Pro-Resolving Lipid Mediators in Colorectal Cancer-Associated Inflammation: Implications for Therapeutic Strategies

“…One of the master regulators of CRC-associated inflammation is Interleukin 1 β (IL1β). IL1β participates in the activation of Nuclear Factor Kappa-light-chain-enhancer of activated B cells (NF-κB)-driver molecular machinery [61] and, for this reason, was classified as pivotal signal molecule contributing to CRC pathogenesis in both preclinical studies, exploiting either the AOM/DSS [62] or the genetic models of CRC [52] and human samples [63], where polymorphisms in its gene and receptors are associated with this disease [64].…”

“…In the following sections, we will highlight studies pointing out resolving ω-3and ω-6-derived lipid mediators as possible molecules for cancer treatment. [64] Preclinical study on APC ∆716 mouse model COX-2 derived AA lipids are essential for tumor growth Calviello et al, 2004 [65] In vitro study on colon cancer cells EPA and DHA block COX-2 expression Fluckiger et al, 2016; Siddiqui et al, 2008 [67,68] In vitro study on colon cancer cells DHA blocks AA-induced proliferation and apoptosis Sarabi et al, 2019 [69] Preclinical study on APC min/+ mouse model and in vitro study on colon cancer cells ω-3 PUFAs enhance apoptosis via specific promoter methylation Liu et al, 2016 [70] Preclinical study on APC…”