OncoDefender-Lynch Syndrome

The OncoDefender – Lynch Syndrome test helps physicians identify patients which have a higher life-time risk of developing several types of cancer and in particular colon cancer. Patients identified by their physicians at high life-time risk of cancer benefit from regular screening and life-style modification.

Lynch Syndrome is a hereditary disorder.  Patients diagnosed with Lynch syndrome face a life-time risk of up to 85% risk of contracting colon cancer.  Women have up to a 65% risk of contracting endometrial cancers. An increased risk exists of contracting a myriad of other cancers including those of the stomach, pancreas, kidney/ureter tract, hepatobiliary tract, gastric tract, prostate, ovaries, gall bladder duct, brain, small intestine and the skin.

Lynch Syndrome is caused by a mutation in a mismatch repair gene in which affected individuals have a higher than normal chance of developing colorectal cancer, endometrial cancer, and various other types of aggressive cancers, often at a young age – also called hereditary non-polyposis colon cancer, (HNPCC).

The mutations of specific genes including but not limited to MLH1, MSH2, MSH6, PMS1 and PMS2 are responsible for Lynch syndrome1 . These genes work in repairing mistakes made when DNA is copied in preparation for cell division. The mutations disallow the repair of DNA mistakes and as cells divide, uncontrollable cell growth may result in cancer.


Footnotes:

1 College of American Pathologists, Prognostic Uses of Microsatellite Testing, May 12, 2011

Additional References:

  1. Klump B, Nehls O, Okech T, et al. Molecular lesions in colorectal cancer: Impact on prognosis? Original data and review of the literature. Int J Colorectal Dis2004; 19:23-42.
  2. American cancer society. Estimated new cases and deaths from colon and rectal cancer in the United States in 2009. Online at www.cancer.org
  3. Grady WM. Genomic instability and colon cancer. Cancer Metastasis Rev 2004, 23:11-27.
  4. Umar et al. Revised Bethesda Guidelines for HNPCC (Lynch Syndrome) and Microsatellite Instability. J Natl Cancer Inst 2004; 96: 261-268.
  5. Popat S, Hubner R, Houlston RS. Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis. J Clin Oncol 2005; 23(3):609-618.
  6. Ribic CM et al. Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer. N Engl J Med. 2003;349(3).
  7. D. J. Sargent, et al. Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC): A pooled molecular reanalysis of randomized chemotherapy trials. J Clin Oncol 2008; 26 (May 20 suppl; abstr 4008).
  8. P L Barratt et al. DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study. Lancet 2002; 360: 1381–91.
  9. Kerr et al. A quantitative multi-gene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in 4 large studies and results of the independent, prospectively-designed QUASAR validation study. J Clin Oncol, 2009 ASCO Annual Meeting Proceedings. 2009;27(15S): 4000.
  10. PR Newswire. Genomic Health's Oncotype DX Colon Cancer Test Predicts Individualized Recurrence Risk for Stage II Colon Cancer Patients. March 14, 2009. http://www.cancercompass.com/cancer-news/1,15698,00.htm
  11. Bertagnolli MM et al., Microsatellite Instability Predicts Improved Response to Adjuvant Therapy With Irinotecan, Fluorouracil, and Leucovorin in Stage III Colon Cancer: Cancer and Leukemia Group B Protocol 89803. J Clin Oncol, 2009;17(11).
  12. Marcus VA, Madlensky L, Gryfe R, Kim H, So K, Millar A, et al. Immunohistochemistry for hMLH1 and hMSH2: a practical test for DNA mismatch repair deficient tumors. Am J Surg Pathol 1999;23:1248–55.
  13. Lindor NM, Burgart LJ, Leontovich O, et al: Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol2002;20: 1043-1048.
  14. Boland CR, Thibodeau SN, Hamilton SR et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58(22):5248-57.
  15. Palomaki GE, Mc Clain MR, Melillo S et al: EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch Syndrome. Genetics in Medicine, 2009: 42(11).