Korean J Gastroenterol.  2010 Aug;56(2):78-82. 10.4166/kjg.2010.56.2.78.

Study on Association between an H-RAS Gene Polymorphism and Gastric Cancer Development

• Song HJ
• Pyun JA
• Lee KJ
• Cho SW
• Kwack KB

• KMID: 1775861
• DOI: http://doi.org/10.4166/kjg.2010.56.2.78

Abstract

BACKGROUND/AIMS
Oncogenic RAS gene mutations have been frequently observed in many tumor types, and their associations with various cancers were reported. This study was conducted to evaluate the association between H-RAS T81C polymorphism and gastric cancer development.
METHODS
H-RAS T81C polymorphism was genotyped in 321 chronic gastritis (ChG) and 151 gastric cancer (GC) patients using GoldenGate(R) Assay kit. Logistic regression analysis adjusted for age and gender was performed to identify the differences of genotype and allele distributions between the each group.
RESULTS
All ChG and GC patients were in Hardy-Weinberg equilibrium. When the frequencies of H-RAS T81C genotype in each group were compared, the homozygous type of major allele TT was more frequent in GC group (62.9%) than ChG group (57.3%), while the frequencies of heterozygous type TC and homozygous type of minor allele CC were higher in ChG group than GC group (39.3% vs. 33.8%, 3.4% vs. 3.3%, respectively). In the results of logistic regression analyses adjusted for age and gender, the odds ratios were 0.845 (0.604-1.182), 0.799 (0.556-1.147), 0.741 (0.493-1.114) and 1.094 (0.366-3.270) for allele, codominant, dominant and recessive models, respectively. However, significant difference was not observed between two groups in any models.
CONCLUSIONS
H-RAS T81C polymorphism was not associated with gastric cancer development in a Korean population.

Keyword

Stomach neoplasm; Polymorphism, Genetic; H-RAS gene

MeSH Terms

Adult
Aged
Alleles
Amino Acid Substitution
Chronic Disease
Female
Gastritis/genetics
Genetic Predisposition to Disease
Genotype
Humans
Logistic Models
Male
Middle Aged
*Polymorphism, Single Nucleotide
Republic of Korea
Stomach Neoplasms/*genetics
ras Proteins/*genetics

Reference

1. Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006; 12:354–362.

2. Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med. 1995; 333:32–41.

3. De Feo E, Persiani R, La Greca A, et al. A case-control study on the effect of p53 and p73 gene polymorphisms on gastric cancer risk and progression. Mutat Res. 2009; 675:60–65.

4. Zhang Y, Jin M, Liu B, et al. Association between H-RAS T81C genetic polymorphism and gastrointestinal cancer risk: a population based case-control study in China. BMC Cancer. 2008; 8:256.

5. Hussain SK, Mu LN, Cai L, et al. Genetic variation in immune regulation and DNA repair pathways and stomach cancer in China. Cancer Epidemiol Biomarkers Prev. 2009; 18:2304–2309.

6. Shibata T, Tahara T, Hirata I, Arisawa T. Genetic polymorphism of interleukin-17A and -17F genes in gastric car-cinogenesis. Hum Immunol. 2009; 70:547–551.

7. Malumbres M, Pellicer A. RAS pathways to cell cycle control and cell transformation. Front Biosci. 1998; 3:d887–d912.

8. Barbacid M. Ras genes. Annu Rev Biochem. 1987; 56:779–827.

9. Taparowsky E, Suard Y, Fasano O, Shimizu K, Goldfarb M, Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982; 300:762–765.

10. Hyten DL, Song Q, Choi IY, et al. High-throughput genotyping with the GoldenGate assay in the complex genome of soybean. Theor Appl Genet. 2008; 116:945–952.

11. Yoo J, Park SY, Robinson RA, Kang SJ, Ahn WS, Kang CS. Ras gene mutations and expression of Ras signal transduction mediators in gastric adenocarcinomas. Arch Pathol Lab Med. 2002; 126:1096–1100.

12. Crespo P, Leó n J. Ras proteins in the control of the cell cycle and cell differentiation. Cell Mol Life Sci. 2000; 57:1613–1636.

13. Langdon JA, Armour JA. Evolution and population genetics of the H-ras minisatellite and cancer predisposition. Hum Mol Genet. 2003; 12:891–900.

14. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003; 3:11–22.

15. Takayama T, Miyanishi K, Hayashi T, Sato Y, Niitsu Y. Colorectal cancer: genetics of development and metastasis. J Gastroenterol. 2006; 41:185–192.

16. Keller JW, Franklin JL, Graves-Deal R, Friedman DB, Whitwell CW, Coffey RJ. Oncogenic KRAS provides a uniquely powerful and variable oncogenic contribution among RAS family members in the colonic epithelium. J Cell Physiol. 2007; 210:740–749.

17. Kiaris H, Spandidos DA, Jones AS, Vaughan ED, Field JK. Mutations, expression and genomic instability of the H-ras protooncogene in squamous cell carcinomas of the head and neck. Br J Cancer. 1995; 72:123–128.

18. Fujita J, Kraus MH, Onoue H, et al. Activated H-ras onco-genes in human kidney tumors. Cancer Res. 1988; 48:5251–5255.

19. Fitzgerald JM, Ramchurren N, Rieger K, et al. Identification of H-ras mutations in urine sediments complements cytology in the detection of bladder tumors. J Natl Cancer Inst. 1995; 87:129–133.

20. Czerniak B, Cohen GL, Etkind P, et al. Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in urinary bladder carcinomas. Hum Pathol. 1992; 23:1199–1204.

21. Zhu D, Xing D, Shen X, Liu J. A method to quantitatively detect H-ras point mutation based on electrochemilumine-scence. Biochem Biophys Res Commun. 2004; 324:964–969.

22. Ohuchi N, Hand PH, Merlo G, et al. Enhanced expression of c-Ha-ras p21 in human stomach adenocarcinomas defined by immunoassays using monoclonal antibodies and in situ hybridization. Cancer Res. 1987; 47:1413–1420.

23. Bohle RM, Brettreich S, Repp R, Borkhardt A, Kosmehl H, Alt-mannsberger HM. Single somatic ras gene point mutation in soft tissue malignant fibrous histiocytomas. Am J Pathol. 1996; 148:731–738.

24. Cohen JB, Broz SD, Levinson AD. Expression of the H-ras protooncogene is controlled by alternative splicing. Cell. 1989; 58:461–472.

25. Guil S, Gattoni R, Carrascal M, Abiá n J, Sté venin J, Bach-Elias M. Roles of hnRNP A1, SR proteins, and p68 helicase in c-H-ras alternative splicing regulation. Mol Cell Biol. 2003; 23:2927–2941.

26. Castro P, Soares P, Gusmã o L, Seruca R, Sobrinho-Simõ es M. H-RAS 81 polymorphism is significantly associated with aneuploidy in follicular tumors of the thyroid. Oncogene. 2006; 25:4620–4627.

27. Sugimura H, Caporaso NE, Modali RV, et al. Association of rare alleles of the Harvey ras protooncogene locus with lung cancer. Cancer Res. 1990; 50:1857–1862.

28. Johne A, Roots I, Brockmö ller J. A single nucleotide polymorphism in the human H-ras protooncogene determines the risk of urinary bladder cancer. Cancer Epidemiol Biomarkers Prev. 2003; 12:68–70.

29. Sathyan KM, Nalinakumari KR, Abraham T, Kannan S. Influence of single nucleotide polymorphisms in H-Ras and cyclin D1 genes on oral cancer susceptibility. Oral Oncol. 2006; 42:607–613.