Has-miR-196a2 rs11614913 has been found to be associated with an significantly increased cancer risk in the variant TC heterozygote, CC homozygote and TC/CC genotype as opposed to the TT wild-type homozygote, in a meta-analysis by Chu et al[1].. More recently, Xu et al. [2]published a meta-analysis examing the roles of both rs11614913 and has-miR-146a rs2910164. Xu’s results have suggested that rs11614913 TT genotype most likely contributes to decreased susceptibility to cancer. Besides, the C allele of rs2910164 might be associated with a protection from digestive cancer.
We performed a similar meta-analysis almost at the same time with Xu et al. and Chu et al.. Our results was consistent with the previous two papers in relevant to rs11614913. However, the results concerning rs2910164 were quite different from those of Xu’s.
Primarily, we got 17 eligible articles [3-19]through literature searching (last search update to May, 2011), while Xu’s only got 10 [3, 5, 8, 10-16]. In Xu’s paper, C allele of rs2910164 has shown a marginal significant protective effect in digestive system neoplasms(CC vs. GG OR=0.63, 95%CI=0.39-1.03; GC vs. GG OR=0.89, 95%CI=0.77-1.04), however in our paper, these marginally significances no longer exist. Moreover, we have obtained more articles, therefore we can generate a new subgroup, the ‘urogenital system neoplasms’ out of overall cancer, which hasn’t been done by Xu. Our results suggested that the protective effect of C allele presented at a borderline level in urogenital system neoplasms in all three models (dominant model CC/CG vs. GG: OR=0.86, 95%CI = 0.73-1.01; recessive model CC vs. CG/GG: OR=0.83, 95%CI=0.66-1.05; homozygote model CC vs. GG: OR=0.76, 95%CI=0.56-1.04). Otherwise, no significant associations were observed.
We believe our results might be more reliable. When the OR for C allelic genetic association was assumed to be 0.8, our analysis reached statistical power of 97.1% for digestive system cancer, and 80% for urogenital system cancer. Under the same condition, Xu’s power for digestive system cancer was only 76%. Xu et al. hasn’t included all the studies published to date, therefore they have ‘lost’ 1202 cases and 1347 controls in the category of digestive system cancer. Of the missed 7 articles, 5 were published between the year 2008 to 2010. Xu et al. should have found all of them if carefully searched the database.
Our conclusion is, the C variant of microRNA146a G>C rs2910164 might associate with reduced risk of urogenital system neoplasms. Further well-designed studies with large sample size are needed to confirm our current findings.




References
1. Chu H, Wang M, Shi D, Ma L, Zhang Z, Tong N, Huo X, Wang W, Luo D, Gao Y: Hsa-miR-196a2 Rs11614913 Polymorphism Contributes to Cancer Susceptibility: Evidence from 15 Case-Control Studies. PLoS One 2011, 6(3):e18108.
2. Xu W, Xu J, Liu S, Chen B, Wang X, Li Y, Qian Y, Zhao W, Wu J: Effects of Common Polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on Cancer Susceptibility: A Meta-Analysis. PLoS One 2011, 6(5):e20471.
3. Catucci I, Yang R, Verderio P, Pizzamiglio S, Heesen L, Hemminki K, Sutter C, Wappenschmidt B, Dick M, Arnold N et al: Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases. Hum Mutat 2009, 31(1):E1052-1057.
4. George GP, Gangwar R, Mandal RK, Sankhwar SN, Mittal RD: Genetic variation in microRNA genes and prostate cancer risk in North Indian population. Mol Biol Rep 2011, 38(3):1609-1615.
5. Guo H, Wang K, Xiong G, Hu H, Wang D, Xu X, Guan X, Yang K, Bai Y: A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han. Fam Cancer 2010, 9(4):599-603.
6. Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F, Zhang Y, Paranjape T, Zhu Y: microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res 2009, 69(14):5970-5977.
7. Horikawa Y, Wood CG, Yang H, Zhao H, Ye Y, Gu J, Lin J, Habuchi T, Wu X: Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma. Clin Cancer Res 2008, 14(23):7956-7962.
8. Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J, Miao R, Wang Y, Wang X, Shen H: Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat 2009, 30(1):79-84.
9. Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A: Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A 2008, 105(20):7269-7274.
10. Liu Z, Li G, Wei S, Niu J, El-Naggar AK, Sturgis EM, Wei Q: Genetic variants in selected pre-microRNA genes and the risk of squamous cell carcinoma of the head and neck. Cancer 2010, 116(20):4753-4760.
11. Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, Yonemura J, Ishizuka T, Arisawa T, Hirata I: Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter 2010, 15(6):524-531.
12. Pastrello C, Polesel J, Della Puppa L, Viel A, Maestro R: Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1/BRCA2-negative familial breast and ovarian cancer patients. Carcinogenesis 2010, 31(12):2124-2126.
13. Srivastava K, Srivastava A, Mittal B: Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population. J Hum Genet 2010, 55(8):495-499.
14. Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, Liang J, Liu P, Zhou X, Miao R et al: A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev 2009, 18(4):1183-1187.
15. Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W et al: A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 2010, 70(5):467-472.
16. Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM: A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 2008, 29(11):2126-2131.
17. Yang H, Dinney CP, Ye Y, Zhu Y, Grossman HB, Wu X: Evaluation of genetic variants in microRNA-related genes and risk of bladder cancer. Cancer Res 2008, 68(7):2530-2537.
18. Ye Y, Wang KK, Gu J, Yang H, Lin J, Ajani JA, Wu X: Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk. Cancer Prev Res (Phila) 2008, 1(6):460-469.
19. Zeng Y, Sun QM, Liu NN, Dong GH, Chen J, Yang L, Wang B: Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol 2010, 16(28):3578-3583.