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Functional genomics of the CDKN2A/B locus in cardiovascular and metabolic disease: what have we learned from GWASs?心血管代谢疾病中 CDKN2A/B 基因座的功能基因组学：GWAS 研究告诉了我们什么？
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Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers.12p11、12q24、9p21、9q31.2 及 ZNF365 上的常见变异与 BRCA1 和/或 BRCA2 突变携带者的乳腺癌风险相关。
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CDKN2A/B基因中的一种基因变异与乳腺癌风险增加相关。

A genetic variant in CDKN2A/B gene is associated with the increased risk of breast cancer.

作者信息

ShahidSales Soodabeh, Mehramiz Mehraneh, Ghasemi Faezeh, Aledavood Amir, Shamsi Mehri, Hassanian Seyed Mahdi, Ghayour-Mobarhan Majid, Avan Amir

机构信息

Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Clin Lab Anal. 2018 Jan;32(1). doi: 10.1002/jcla.22190. Epub 2017 Mar 9.

DOI:10.1002/jcla.22190
PMID:28276595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6817096/
Abstract

BACKGROUND

Breast cancer is among the leading cause of cancer-related-deaths in women, supporting the need for the identification of novel prognostic and predictive biomarkers. Recent studies have identified common genetic variants in a region on chromosome 9p21 associated with an increased risk of developing different cancers. Here, we explored the association of a genetic variant in CDKN2A/B, rs10811661, for the first time in 564 subjects with/without breast cancer.

METHOD

Genotyping was performed using TaqMan real time PCR method. The associations of this genetic variant with breast cancer risk and pathological information of patients were assessed.

RESULTS

We observed that patients with breast cancer had a higher frequency of TT genotype (P<.001) than control group, which was associated with advanced TNM classification (P=.04) and larger tumor size (P=.014), as detected by the recessive genetic inheritance model. Moreover, the logistic regression under recessive genetic model revealed that breast cancer patients with TT had higher risk of breast cancer, compared to CC/CT genotypes (eg, OR=4.9, 95% CI:1.9-12, P=.001), after adjusted for potential confounders, age, BMI, and family history.

CONCLUSION

We demonstrated that patients carrying the TT genotype for CDKN2A/B rs10811661 polymorphism had the increased risk of breast cancer susceptibility. However, further investigations are warranted in a larger and prospective setting to explore the value of this marker as a risk stratification marker in breast cancer.

摘要

背景

乳腺癌是女性癌症相关死亡的主要原因之一，这表明需要鉴定新的预后和预测生物标志物。最近的研究已经在9号染色体p21区域鉴定出与患不同癌症风险增加相关的常见基因变异。在此，我们首次在564名有/无乳腺癌的受试者中探究了CDKN2A/B基因变异rs10811661的相关性。

方法

采用TaqMan实时PCR方法进行基因分型。评估该基因变异与乳腺癌风险及患者病理信息的相关性。

结果

我们观察到，乳腺癌患者中TT基因型的频率高于对照组（P<0.001），根据隐性遗传模型检测，这与晚期TNM分类（P=0.04）和更大的肿瘤大小（P=0.014）相关。此外；在隐性遗传模型下的逻辑回归显示，在调整了潜在混杂因素、年龄、体重指数和家族史后，与CC/CT基因型相比，携带TT基因型的乳腺癌患者患乳腺癌的风险更高（例如，OR=4.9，95%CI：1.9-12，P=0.001）。

结论

我们证明，携带CDKN2A/B rs10811661多态性TT基因型的患者患乳腺癌的易感性增加。然而，需要在更大规模的前瞻性研究中进一步探究该标志物作为乳腺癌风险分层标志物的价值。