DOI QR코드

DOI QR Code

Promoter Methylation Status of DNA Repair Gene (hMLH1) in Gastric Carcinoma Patients of the Kashmir Valley

  • Wani, Majid ;
  • Afroze, Dil ;
  • Makhdoomi, Muzamil ;
  • Hamid, Iqra ;
  • Wani, Bilal ;
  • Bhat, Gulzar ;
  • Wani, Rauf ;
  • Wani, Khursheed
  • Published : 2012.08.31

Abstract

Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age ($mean{\pm}S.D$) $50{\pm}11.4$ years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001).We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley.

Keywords

Gastric cancer;promoter hypermethylation;CpG;MMR;Kashmir valley

References

  1. Aarnio M, Mecklin JP, Aaltonen LA, Nystrom-Lahti M, Jarvinen HJ (1995). Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer, 64, 430-3. https://doi.org/10.1002/ijc.2910640613
  2. Adloff M, Arnaud JP, Schloegel M, Thibaud D, Bergamaschi R (1986). Colorectal cancer in patients under 40 years of age. Dis Colon Rectum, 29, 322-5. https://doi.org/10.1007/BF02554121
  3. Ajao OG, Adenuga MO, Ladipo JK (1988). Colorectal carcinoma in patients under the age of 30 years: a review of 11 cases. J R Coll Surg Edinb, 33, 277-9.
  4. Al-Jaberi TM, Yaghan RJ, El-Heis HA (2003). Colorectal cancer in young patients under 40 years of age. Comparison with old patients in a well defined Jordanian population. Saudi Med J, 24, 871-4.
  5. Ansari R, Mahdavinia M, Sadjadi A, et al (2006). Incidence and age distribution of colorectal cancer in Iran: Results of a population-based cancer registry. Cancer Letters, 240, 143-7. https://doi.org/10.1016/j.canlet.2005.09.004
  6. Atkin W S, Edwards R, Kralj-Hans I, et al (2010). Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet, 375, 1624-33. https://doi.org/10.1016/S0140-6736(10)60551-X
  7. Bedikian AY, Kantarjian H, Nelson RS, Stroehlein JR, Bodey GP (1981). Colorectal cancer in young adults. South Med J, 74, 920-4. https://doi.org/10.1097/00007611-198108000-00007
  8. Bener A, Moore MA, Ali R, El Ayoubi HR (2010). Impacts of family history and lifestyle habits on colorectal cancer risk: a case-control study in Qatar. Asian Pac J Cancer Prev, 11, 963-8.
  9. de Silva MV, Fernando MS, Fernando D (2000). Comparison of some clinical and histological features of colorectal carcinoma occurring in patients below and above 40 years. Ceylon Med J, 45, 166-8.
  10. Devroede GJ, Taylor WF, Sauer WG, Jackman RJ, Stickler G B. (1971). Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med, 285, 17-21. https://doi.org/10.1056/NEJM197107012850103
  11. Domergue J, Ismail M, Astre C, et al (1988). Colorectal carcinoma in patients younger than 40 years of age. Montpellier Cancer Institute experience with 78 patients. Cancer, 61, 835-40. https://doi.org/10.1002/1097-0142(19880215)61:4<835::AID-CNCR2820610432>3.0.CO;2-X
  12. Ferlay J, Shin H, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer.
  13. Gallagher E, Zeigler MG (1972). Rectal carcinoma in patients in second and third decades of life. Am J Surgery, 124, 655-???. https://doi.org/10.1016/0002-9610(72)90106-7
  14. Griffin PM, Liff JM, Greenberg RS, Clark WS (1991). Adenocarcinomas of the colon and rectum in persons under 40 years old. A population-based study. Gastroenterology, 100, 1033-40. https://doi.org/10.1016/0016-5085(91)90279-T
  15. Hampel H, Peltomaki P (2000). Hereditary colorectal cancer: risk assessment and management. Clinical Genetics, 58, 89-97.
  16. Herszenyi L, Miheller P, Tulassay Z (2007). Carcinogenesis in inflammatory bowel disease. Dig Dis, 25, 267-9. https://doi.org/10.1159/000103898
  17. Isbister WH (1992). Colorectal cancer below age 40 in the Kingdom of Saudi Arabia. Aust N Z J Surg, 62, 468-72. https://doi.org/10.1111/j.1445-2197.1992.tb07227.x
  18. Isbister WH, Fraser J (1990). Large-bowel cancer in the young: a national survival study. Dis Colon Rectum, 33, 363-6. https://doi.org/10.1007/BF02156258
  19. Jensen HK, Konradsen F, Jors E, Petersen JH, Dalsgaard A (2011). Pesticide use and self-reported symptoms of acute pesticide poisoning among aquatic farmers in phnom penh, Cambodia. J Toxicol, 63, 981-4.
  20. Jarvinen HJ, Mecklin JP, Sistonen P (1995). Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology, 108, 1405-11. https://doi.org/10.1016/0016-5085(95)90688-6
  21. Liu B, Farrington SM, Petersen GM, et al (1995). Genetic instability occurs in the majority of young patients with colorectal cancer. Nat Med, 1, 348-52. https://doi.org/10.1038/nm0495-348
  22. MacGillivray DC, Swartz SE, Robinson AM, Cruess DF, Smith LE (1991). Adenocarcinoma of the colon and rectum in patients less than 40 years of age. Surg Gynecol Obstet, 172, 1-7.
  23. Martin EW, Joyce S, Lucas J, Clausen K, Cooperman M (1981). Colorectal carcinoma in patients less than 40 years of age: pathology and prognosis. Dis Colon Rectum, 24, 25-8. https://doi.org/10.1007/BF02603445
  24. McCart AE, Vickaryous NK, Silver A (2008). Apc mice: Models, modifiers and mutants. Pathology Res Pract, 204, 479-90. https://doi.org/10.1016/j.prp.2008.03.004
  25. Meyer JE, Narang T, Schnoll-Sussman F H, et al (2010). Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database. Cancer, 116, 4354-9. https://doi.org/10.1002/cncr.25432
  26. Noeman SA, Sharada K, El Dardiry S, Rahim AA, Zaki Y (1994). Significance of tumour markers in colorectal carcinoma associated with Schistosomiasis. Bangladesh Med Res Counc Bull, 20, 12-20.
  27. O'Connell JB, Maggard M A, Liu J H, et al (2003). Rates of colon and rectal cancers are increasing in young adults. Am Surg, 69, 866-72.
  28. O'Connell JB, Maggard MA, Livingston EH, Yo CK (2004).Colorectal cancer in the young. Am J Surg, 187, 343-8. https://doi.org/10.1016/j.amjsurg.2003.12.020
  29. Ohman U (1982). Colorectal carcinoma in patients less than 40 years of age. Dis Colon Rectum, 25, 209-14. https://doi.org/10.1007/BF02553102
  30. Okuno M, Ikehara T, Nagayama, M, et al (1987). Colorectal carcinoma in young adults. Am J Surg, 154, 264-8. https://doi.org/10.1016/0002-9610(89)90606-5
  31. Peters RK, Garabrant DH, Yu MC, Mack TM (1989). A casecontrol study of occupational and dietary factors in colorectal cancer in young men by subsite. Cancer Res, 49, 5459-68.
  32. Pratt CB, Rivera G, Shanks E, et al (1977). Colorectal carcinoma in adolescents implications regarding etiology. Cancer, 40, 2464-72. https://doi.org/10.1002/1097-0142(197711)40:5+<2464::AID-CNCR2820400912>3.0.CO;2-D
  33. Sampson JR, Jones S, Dolwani S, Cheadle JP (2005). MutYH (MYH) and colorectal cancer. Biochem Soc Trans, 33, 679-83. https://doi.org/10.1042/BST0330679
  34. Siegel RL, Jemal A, Ward EM (2009). Increase in incidence of colorectal cancer among young men and women in the United States. Cancer Epidemiol Biomarkers Prev, 18, 1695-8. https://doi.org/10.1158/1055-9965.EPI-09-0186
  35. Singh Y, Vaidya P, Hemandas AK, Singh KP, Khakurel M (2002). Colorectal carcinoma in Nepalese young adults: presentation and outcome. Gan To Kagaku Ryoho, 29, 223-9.
  36. Soliman AS, Bondy ML, Levin B, et al (1997). Colorectal cancer in Egyptian patients under 40 years of age. Int J Cancer, 71, 26-30. https://doi.org/10.1002/(SICI)1097-0215(19970328)71:1<26::AID-IJC6>3.0.CO;2-5
  37. Urbani C, Sinoun M, Socheat D, et al (2002). Epidemiology and control of Mekongi schistosomiasis. Acta Trop, 82, 157-68. https://doi.org/10.1016/S0001-706X(02)00047-5
  38. van Lier MG, Wagner A, Mathus-Vliegen EM, et al (2001). High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol, 105, 1258-64.
  39. Yilmazlar T, Zorluoglu A, Ozguc H, et al (1995). Colorectal cancer in young adults. Tumori, 81, 230-33.

Cited by

  1. Adjuvant Radiotherapy for Gastric Carcinoma: 10 years Follow-up of 244 cases from a Single Institution vol.15, pp.20, 2014, https://doi.org/10.7314/APJCP.2014.15.20.8871
  2. Methylation-mediated gene silencing as biomarkers of gastric cancer: A review vol.20, pp.34, 2014, https://doi.org/10.3748/wjg.v20.i34.11991
  3. Genetic unraveling of colorectal cancer vol.35, pp.6, 2014, https://doi.org/10.1007/s13277-014-1713-7
  4. RETRACTED ARTICLE: Role of p16 gene promoter methylation in gastric carcinogenesis: a meta-analysis vol.41, pp.7, 2014, https://doi.org/10.1007/s11033-014-3319-y
  5. MGMT-B Gene Promoter Hypermethylation in Patients with Inflammatory Bowel Disease - A Novel Finding vol.16, pp.5, 2015, https://doi.org/10.7314/APJCP.2015.16.5.1945
  6. Prevalência de sinais e sintomas digestórios em trabalhadoras rurais e fatores associados vol.28, pp.5, 2015, https://doi.org/10.1590/1982-0194201500077
  7. Biomarkers for gastric cancer: Progression in early diagnosis and prognosis (Review) pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.2959
  8. Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer vol.8, pp.4, 2014, https://doi.org/10.3892/ol.2014.2410
  9. Association Between hMLH1 Promoter Methylation and Risk of Gastric Cancer: A Meta-Analysis vol.9, pp.1664-042X, 2018, https://doi.org/10.3389/fphys.2018.00368