Abstract
MicroRNAs are a new class of non-proteincoding, small RNAs that function as tumor suppressors or oncogenes. They participate in diverse biological pathways and function as gene regulators. A G>C polymorphism (rs2910164), which is located in the sequence of miR-146a precursor, results in a change from G:U to C:U in its stem region. However, it remains largely unknown whether this single nucleotide polymorphism (SNP) may alter esophageal squamous cell carcinoma (ESCC) susceptibility. In the current study, we evaluated association between rs2910164 and ESCC susceptibility in a case–control study of 444 sporadic ESCC patients and 468 matched cancer-free controls in a Chinese Han population. Compared with rs2910164 variant genotype CC, genotype GG was associated with increased risk of ESCC (Odds Ratio, 2.39, 95% Confidence Interval, 1.36–4.20). In the smokers, the risk of rs2910164 GG genotype was more notable (Odds Ratio, 3.17, 95% Confidence Interval, 1.71–4.46). In the stratification analyses, we also found there was a strong correlation between rs2910164 C/G variant and the clinical TNM stage (P < 0.01). These findings suggest that this functional SNP in pre-miR-146a could contribute to ESCC susceptibility and clinical outcome.
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Abbreviations
- ESCC:
-
Esophageal squamous cell carcinoma
- miRNA:
-
MicroRNA
- SNP:
-
Single nucleotide polymorphism
References
Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150
Pickens A, Orringer MB (2003) Geographical distribution and racial disparity in esophageal cancer. Ann Thorac Surg 76:S1367–S1369
Enzinger PC, Mayer RJ (2004) Esophageal cancer. N Engl J Med 349:2241–2252
Bartel DP, Chen CZ (2004) Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 5:396–400
Shen J, Ambrosone CB, DiCioccio RA et al (2008) A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29:1963–1966
Jazdzewski K, Murray EL, Franssila K et al (2008) Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105:7269–7274
Xu B, Feng NH, Li PC et al (2010) A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 70:467–472
Xu T, Zhu Y, Wei QK et al (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29:2126–2131
Hu Z, Liang J, Wang Z et al (2009) Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat 30:79–84
Tian T, Shu Y, Chen J et al (2009) A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev 18:1183–1187
Volinia S, Calin GA, Liu CG et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103:2257–2261
Guo Y, Chen Z, Zhang L et al (2008) Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res 68:26–33
Taganov KD, Boldin MP, Chang KJ et al (2006) NF-kappaB-dependent induction of microRNA mir-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486
Jazdzewski K, Liyanarachchi S, Swierniak M et al (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106:1502–1505
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 30872549 and No. 30971603) and Natural Science Foundation Project of CQ CSTC (No. 2009BA5013).
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We declare that there is no Conflict of interest.
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Hong Guo and Kai Wang contributed equally to this work.
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Guo, H., Wang, K., Xiong, G. et al. A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han. Familial Cancer 9, 599–603 (2010). https://doi.org/10.1007/s10689-010-9370-5
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DOI: https://doi.org/10.1007/s10689-010-9370-5