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NF?B1 and NF?BIA polymorphisms are associated with increased risk for sporadic colorectal cancer in a southern Chinese population.

ABSTRACT: Nuclear factor ?B (NF?B) plays a key role in the regulation of apoptosis. The function of NF?B is inhibited by binding to NF?B inhibitor (I?B), and disruption of the balance of NF?B and I?B is related to the development of many diseases, including tumors. Therefore, we hypothesized that the NF?B1 (-94del/insATTG) and NF?BIA (2758 A>G) polymorphisms were associated with colorectal cancer (CRC) susceptibility.In a hospital-based case-control study of 1001 CRC patients and 1005 cancer-free controls frequency matched by age and sex, we genotyped polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and performed luciferase assays and Western blotting analysis to identify whether genetic variants in NF?BIA alter its gene expressions and functions and thus cancer risk.We found that both NF?B1-94 ins/delATTG and NF?BIA 2758 A>G polymorphisms were correlated with CRC risk (OR?=?1.47; 95%CI?=?1.14-1.86, and OR?=?1.38; 95% CI?=?1.14-1.66, respectively). Furthermore, when evaluated these two polymorphisms together, the combined genotypes with 2 variant (risk) alleles (2758GG and -94ins/ins+del/ins) were associated with an increased risk of CRC (OR?=?1.71; 95% CI?=?1.23-2.38) compared to 0 variant, and the significant trend for 2 variant (risk) alleles were more pronounced among subgroups of aged <60 years, women, never drinkers, never smokers, persons with a normal BMI and those with a family history of cancer(P(trend)<0.01). Moreover, luciferase assays showed that the G allele in the 3'UTR significantly decreased NF?BIA mRNA stability and the A allele regulation by miRNA449a in vitro and that the NF?BIA protein expression levels of the AA+AG variant carriers were significantly higher in peritumoral tissues than those of the 2758GG genotype.NF?B1 and NF?BIA polymorphisms appear to jointly contribute to risk of CRC. These two variants may be a genetic modifier for CRC susceptibility in this southern Chinese population.

SUBMITTER: Song S

PROVIDER: S-EPMC3128094 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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NFκB1 and NFκBIA polymorphisms are associated with increased risk for sporadic colorectal cancer in a southern Chinese population.

Song Shunxin S Chen Dianke D Lu Jiachun J Liao Jiawei J Luo Yanxin Y Yang Zuli Z Fu Xinhui X Fan Xinjuan X Wei Yisheng Y Yang Lei L Wang Lei L Wang Jianping J

PloS one 20110630 6

<h4>Background</h4>Nuclear factor κB (NFκB) plays a key role in the regulation of apoptosis. The function of NFκB is inhibited by binding to NFκB inhibitor (IκB), and disruption of the balance of NFκB and IκB is related to the development of many diseases, including tumors. Therefore, we hypothesized that the NFκB1 (-94del/insATTG) and NFκBIA (2758 A>G) polymorphisms were associated with colorectal cancer (CRC) susceptibility.<h4>Methods</h4>In a hospital-based case-control study of 1001 CRC pat ...[more]

PMID: 21738780

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Project description:BACKGROUND: B7-H4, a co-inhibitory molecule of the B7 family, can restrain T cell proliferation, cytokine secretion and the development of cytotoxicity. B7-H4 is expressed in tumor tissues at a higher level than in normal tissues, and has a potential effect to protect tumors from anti-tumor immune responses. This case-control study was carried out to determine the potential influences of B7-H4 gene polymorphisms on the susceptibility and progression of breast cancer in Han women of Northeast China. METHODS: We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414) and tagged all common haplotypes (frequency greater than or equal to 1%) in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the genotypes. RESULTS: Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively). The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively). Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881), but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031). And the AAA and the GCG haplotypes also respectively have significant influences on tumor size and ER status. CONCLUSION: These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.

Dataset Information

NF?B1 and NF?BIA polymorphisms are associated with increased risk for sporadic colorectal cancer in a southern Chinese population.

Publications

NFκB1 and NFκBIA polymorphisms are associated with increased risk for sporadic colorectal cancer in a southern Chinese population.

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