Hereditary nonpolyposis colorectal cancer risk factors

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Overview

The most potent risk factor in the development of hereditary nonpolyposis colorectal cancer is gene mutations caused by defective DNA mismatch repair. There are no other risk factors associated with this condition.[1]

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Genetics

The 4 main MMR genes associated with Lynch syndrome are MLH1, MSH2, MSH6 and PMS2. Most mutations (90%) that cause Lynch syndrome are found in the MLH1 or MSH2 genes. The other 2 genes, MSH6 and PMS2, and possibly others, account for the other 10% of mutations.[2]

Individuals with HNPCC have about an 80% lifetime risk for colon cancer. Two-thirds of these cancers occur in the proximal colon. The mean age of colorectal cancer diagnosis is 44 for members of families that meet the Amsterdam criteria. Also, women with HNPCC have an 80% lifetime risk of endometrial cancer. The average age of diagnosis of endometrial cancer is about 46 years. Among women with HNPCC who have both colon and endometrial cancer, about half present first with endometrial cancer, making endometrial cancer the most common sentinel cancer in Lynch syndrome.[12] In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40 years. Other HNPCC-related cancers have been reported with specific features: the urinary tract cancers are transitional carcinoma of the ureter and renal pelvis; small bowel cancers occur most commonly in the duodenum and jejunum; the central nervous system tumor most often seen is glioblastoma.[3]

References

  1. Si JW, Wang L, Ba XJ, Zhang X, Dong Y, Zhang JX, Li WT, Li T (2015). "[Clinicopathological screening of Lynch syndrome: a report of 2 cases and literature review]". Beijing Da Xue Xue Bao (in Chinese). 47 (5): 858–64. PMID 26474631.
  2. Lynch Syndrome. Canadian Cancer Society http://www.cancer.ca/en/cancer-information/cancer-101/what-is-a-risk-factor/genetic-risk/lynch-syndrome/?region=ab#ixzz3t69IQ9M7 Accessed on December,01 2015
  3. Lynch Syndrome. Wikipedia https://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer Accessed on December,01 2015


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