KRAS SNPs are related to colorectal cancer susceptibility and survival in Chinese people
Abstract
Aim:KRAS SNPs may increase KRAS transcription and KRAS levels. SNPs of KRAS 3′UTR can affect carcinoma risk and prognosis. Materials & methods: The rs8720 and rs7960917 in KRAS 3′UTR for colorectal carcinoma (CRC) risk and survival were investigated in a case–control study. Association between SNPs and CRC risk, survival analysis were analyzed by an unconditional logistic regression model, log-rank test, Kaplan–Meier estimation, Cox regression model and one-way analysis of variance. Results & conclusion: The genotype CT of rs8720 was significantly increased risk of CRC, decreased overall survival and event-free survival, and KRAS mRNA and protein expressions were significantly increased in individuals with rs8720 CT, TT genotype. rs8720 may be an important factor in CRC development and prognosis.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Longitudinal adherence to colorectal cancer screening guidelines. Am. J. Manag. Care 22(2), 105–111 (2016).
- 2. Race/ethnicity and multiple cancer risk factors among individuals seeking smoking cessation treatment. Cancer Epidemiol. Biomarkers Prev. 17(11), 2937–2945 (2008).
- 3. The long and winding road to useful predictive factors for anti-EGFR therapy in metastatic It is should colorectal carcinoma: the KRAS/BRAF pathway. Oncology 77(Suppl. 1), 57–68 (2009).
- 4. KRAS gene mutations – prognostic factor in colorectal cancer? Rom. J. Morphol. Embryol. 56(Suppl. 2), 671–678 (2015).
- 5. Association between miR-199a rs74723057 and MET rs1621 polymorphisms and the risk of hepatocellular carcinoma. Oncotarget 7(48), 79365–79371 (2016). • Effects of KRAS mutation and polymorphism on the risk and prognosis of oral squamous cell carcinoma.
- 6. Common SNP in premiR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc. Natl Acad. Sci. 105(20), 7269–7274 2008).
- 7. RAS is regulated by the let-7 microRNA family. Cell 120(5), 635–647 (2005). •• It showed us the let-7 microRNA may regulate RAS function and the possible mechanisms.
- 8. A SNP in a let-7 microRNA complementary site in the KRAS 3′UTR increases nonsmall cell cancer risk. Cancer Res. 68(20), 8535–8540 (2008). • The SNPs in the miRNA may regulate the KRAS function by binding KRAS 3′UTR.
- 9. . rs61764370 polymorphism of KRAS and risk of cancer in Caucasian population: a meta-analysis. J. Cancer Res. Ther. 12(2), 699–704 (2016). • A meta-analysis about rs61764370 polymorphism of KRAS and risk of cancer in Caucasian population.
- 10. . Association of rs712 polymorphism in KRAS gene 3′-luntranslated region and cancer risk: a meta-analysis. J. BUON 20, 309–316 (2015).
- 11. KRAS polymorphisms are associated with survival of CRC in Chinese population. Tumour Biol. 37(4), 4727–4734 (2016).
- 12. miR-216b post-transcriptionally downregulates oncogene KRAS and inhibits cell proliferation and invasion in clear cell renal cell carcinoma. Cell. Physiol. Biochem. 49(5), 1755–1765 (2018).
- 13. Prevalence of RAS gene mutations in human colorectal cancers. Nature 327(6120), 293–297 (1987).
- 14. K-RAS gene mutations in adenomas and carcinomas of the colon. Surg. Oncol. 1(4), 275–282 (1992).
- 15. The involvement of KRAS gene 3′-UTR polymorphisms in risk of cancer and influence on patient response to anti-EGFR therapy in metastatic colorectal cancer: a meta-analysis. Onco Targets Ther. 7, 1487–1496 (2014).
- 16. KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer. Mol. Oncol. 9(7), 1341–1347 (2015).
- 17. KRAS mutation status is predictive of response to cetuximab therapy in Collector cancer. Cancer Res. 66(8), 3992–3995 (2006).
- 18. A 3′-untranslated region KRAS variant and triple-negative breast cancer: a case–control and genetic analysis. Lancet Oncol. 12(4), 377–386 (2011).
- 19. Prevalence of the variant allele rs61764370 T>G in the 3′UTR of KRAS among Dutch BRCA1, BRCA2 and non-BRCA1/BRCA2 breast cancer families. Breast Cancer Res. Treat. 128(1), 79–84 (2011). • rs61764370 T>G in the 3′UTR of KRAS in the BRCA1/BRCA2 breast cancer families were different.
- 20. Ovarian Cancer Association Consortium; Breast Cancer Association Consortium; Consortium of Modifiers of BRCA1 and BRCA2, No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecol. Oncol. 141(2), 386–401 (2016).
- 21. A let-7 microRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic Collector cancer treated with cetuximab monotherapy. Ann. Oncol. 22(1), 104–109 (2011). • Let-7 miRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer.
- 22. A let-7 microRNA-binding site polymorphism in the KRAS 3′UTR is associated with reduced survival in oral cancers. Carcinogenesis 30(6), 1003–1007 (2009). • Polymorphism in the KRAS 3′UTR is associated with reduced survival in oral cancers.
- 23. Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan. Pharmacogenomics J. 10(5), 458–464 (2010).
- 24. rs712 polymorphism within let-7 microRNA-binding site might be involved in the initiation and progression of colorectal cancer in Chinese population. Onco Targets Ther. 8, 3041–3045 (2015).
- 25. Association between a functional polymorphism rs712 within let-7-binding site and risk of papillary thyroid cancer. Med. Oncol. 31(10), 221 (2014). • The functional polymorphism rs712 within let-7-binding may affect the risk of papillary thyroid cancer.
- 26. A let-7 binding site polymorphism rs712 in the KRAS 3′ UTR is associated with an increased risk of gastric cancer. Tumour Biol. 34(5), 3159–3163 (2013).
- 27. Effects of KRAS mutation and polymorphism on the risk and prognosis of oral squamous cell carcinoma. Head Neck 34(5), 663–666 (2012).
- 28. Targeted knock-in of the polymorphism rs61764370 does not affect KRAS expression but reduces let-7 levels. Hum. Mutat. 35(2), 208–214 (2014).
- 29. Association between the KRAS gene polymorphisms and papillary thyroid carcinoma in a Chinese Han population. J. Cancer 7(15), 2420–2426 (2016).
- 30. Defective nucleotide excision repair in Xpc mutant mice and its association with cancer predisposition. Mutat. Res. 459(2), 99–108 (2000).