A Functional Genetic Variant at the C-Reactive Protein Promoter (rs3091244) Is Not Associated With Cancer Risk in a Chinese Population.

Background: The association of genetically elevated levels of circulating C-reactive protein (CRP) with cancer risk has been extensively investigated in European populations; however, there are conflicting conclusions. The tri-allelic rs3091244 is a functionally validated genetic variant, and its allelic frequencies differ significantly between European and Asian populations. Here, we examined the association of rs3091244 with cancer risk in a Chinese population. Methods: rs3091244 was genotyped by Sanger sequencing in 4,971 cancer cases and 2,485 controls. The rs1205 and rs2794521 gene variants were also genotyped using TaqMan assays in subgroups. Results: No association was detected between the genotyped CRP variants and cancer risk, with or without distinguishing cancer types, suggesting that circulating CRP is not causally involved in tumorigenesis in Chinese populations.

Mutations of C-reactive protein (CRP) -286 SNP, APC and p53 in colorectal cancer: implication for a CRP-Wnt crosstalk.

C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway.

[The analysis of HLA-A, B and DRB1 allelic polymorphism in Han race population in Lanzhou region of China].

OBJECTIVE: To investigate the HLA-A, B and DRB1 allele polymorphism of the Han race population in Lanzhou area. METHODS: Polymerase chain reaction-sequence specific primer was used to detect HLA-A, B and DRB1 alleles in 200 unrelated healthy Han individuals from Lanzhou region, Northwest China, and the results were compared with those of Han populations in North, South and Northwest China, and Hui, Uigur and Tibetan population in China. RESULTS: Fourteen of alleles were detected and identified for HLA-A; 32 for HLA-B; and 13 for HLA-DRB1. HLA- A*01, A*02,A*11,A*24, A*30, A*31, A*33; HLA- B*13, B*15, B*40, B*44, B*46, B*51, B*58, B*60; HLA- DRB1*04,. DRB1*07, DRB1*08, DRB1*09, DRB1*11, DRB1*12, DRB1*14 and DRB1*15 were the most common alleles. The frequencies of HLA-A, B and DRB1 genes of Lanzhou Han race were close to that of North China Hans and Hui population in Northwest China, and a little different to that of South China Hans. The HLA-DRB1 alleles were significantly different to those of Uigur and Tibetan race population of China. CONCLUSION: The allelic polymorphism of HLA-A,B and DRB1 loci of Han race population in Lanzhou area was between North and South Han race of China, close to Northwest China Hui, and markedly different to Northwest China Uigur and Tibetan race populations.