Genetic association between the cyclin-dependent kinase inhibitor gene p27/Kip1 polymorphism (rs34330) and cancer susceptibility: a meta-analysis

Cheng, Xiao-Ke; Wang, Xuejun; Li, Xiaodong; Ren, Xuequn

doi:10.1038/srep44871

Cited by 5 publications

(3 citation statements)

References 31 publications

(46 reference statements)

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“…For this reason, Lu et al [ 48 ] conducted a meta-analysis including 17 case-control studies enrolling 9038 cases and 11,596 controls and observed that the 109T/G TG genotype had a protective role on cancer. And Cheng et al [ 49 ] also conducted a meta-analysis aiming to verify the association between p27 rs34330 polymorphism and cancer risk; they suggested that rs34330 polymorphism was related to an increased risk of cancer. Here, we reconducted an updated meta-analysis containing 24 case-control studies comprising of 9627 cases and 12,102 controls and identified that p27 -V109G polymorphism was associated with a decreased risk of cancer, which was consistent with Lu et al's work [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

p27-V109G Polymorphism Is Not Associated with the Risk of Prostate Cancer: A Case-Control Study of Han Chinese Men in Central China

et al. 2018

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Objective We conducted an update meta-analysis aiming to verify the association between p27-V109G polymorphism and cancer risk, particular for prostate cancer (PCa). Then, we conducted a case-control study of Han Chinese in central China to verify the evidence-based results. Methods Relevant studies were collected from diverse databases up to March 2017. In addition, a hospital-based (H-B) case-control study enrolling 90 PCa patients and 140 healthy controls was included to verify these evidence-based findings. Genetic risk was calculated by odds ratio (OR) with its corresponding 95% confidence interval (CI). The p27-V109G polymorphism was determined by MassARRAY genotyping method. Results Finally, twenty-four published studies comprising 9627 cases and 12,102 controls were enrolled for the current meta-analysis. Overall analysis suggested that p27-V109G polymorphism decreased overall cancer risk in allelic contrast, heterozygote, and dominant models. When stratified analysis was conducted by ethnicity, data revealed that p27-V109G polymorphism was associated with a decreased cancer risk in Caucasians. Highlighted in the subgroup analysis by cancer type, we uncovered a significantly decreased risk of PCa in allelic contrast, dominant, homogeneous, and recessive models. However, in the validation case-control study, we failed to uncover a positive association between p27-V109G polymorphism and PCa risk. In addition, negative results were also identified when subgroup analyses were stratified by age, tumor grade, tumor stage, PSA levels, and other measurements. Conclusion Although evidence-based results suggest that p27-V109G polymorphism plays a protective role in overall cancer risk, particularly for PCa, our case-control study failed to validate any association between this particular polymorphism and PCa risk.

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Section: Discussionmentioning

confidence: 99%

p27-V109G Polymorphism Is Not Associated with the Risk of Prostate Cancer: A Case-Control Study of Han Chinese Men in Central China

et al. 2018

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“…This is a variant frequently reported in population databases. The T allele has been associated with cancer susceptibility [ 10 , 19 ], and in vitro it confers lower transcription rate of CDKN1B [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

PDP type brain tumor in association with multiple endocrine neoplasia type 1

Einarsson,

Frederiksen,

Pedersen

et al. 2024

Heliyon

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“…The CDKN1B polymorphism at rs34330 has also been associated with susceptibility to multiple cancers including breast, lung, thyroid, endometrial, and hepatocellular cancer, where T is a risk allele (9). CDKN1B signaling promotes apoptosis in SLE patients undergoing bone marrow mesenchymal stem cell transplantation (10).…”

Section: Introductionmentioning

confidence: 99%

Lupus Susceptibility Region Containing CDKN1B rs34330 Mechanistically Influences Expression and Function of Multiple Target Genes, Also Linked to Proliferation and Apoptosis

Singh

Maiti

Zhou

et al. 2021

Arthritis & Rheumatology

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Objective In a recent genome‐wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant. Methods We performed an allelic association analysis in patients with SLE, followed by a meta‐analysis assessing genome‐wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE‐relevant cell lines were applied to determine the functional consequences of rs34330. Results We replicated a genetic association between SLE and rs34330 (meta‐analysis P = 5.29 × 10−22, odds ratio 0.84 [95% confidence interval 0.81–0.87]). Follow‐up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation–real‐time quantitative polymerase chain reaction, we demonstrated substantial allele‐specific promoter and enhancer activity, and allele‐specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC‐binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF‐1]). Chromosome conformation capture revealed long‐range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)–based genome editing. Finally, CRISPR/dead CRISPR‐associated protein 9–based epigenetic activation/silencing confirmed these results. Gene‐edited cell lines also showed higher levels of proliferation and apoptosis. Conclusion Collectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF‐1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.

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Genetic association between the cyclin-dependent kinase inhibitor gene p27/Kip1 polymorphism (rs34330) and cancer susceptibility: a meta-analysis

Cited by 5 publications

References 31 publications

p27-V109G Polymorphism Is Not Associated with the Risk of Prostate Cancer: A Case-Control Study of Han Chinese Men in Central China

p27-V109G Polymorphism Is Not Associated with the Risk of Prostate Cancer: A Case-Control Study of Han Chinese Men in Central China

PDP type brain tumor in association with multiple endocrine neoplasia type 1

Lupus Susceptibility Region Containing CDKN1B rs34330 Mechanistically Influences Expression and Function of Multiple Target Genes, Also Linked to Proliferation and Apoptosis

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