Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch Syndrome) is an inherited predisposition to colorectal cancer and other cancers. The “non-polyposis” stems from the knowledge that this form of bowel cancer can occur with formation of few or no polyps. First named over 100 years ago, it is the most common form of familial colorectal cancer, however only accounts for around 5% of all bowel cancer cases. Other cancers that HNCPP increases the risk of includes: endometrial cancer, duodenal cancer, cancer of the ureter and renal pelvis, ovarian cancer and brain tumours. As yet, prostate cancer is not recognised as part of the syndrome.
The prostate gland is a part of the male human anatomy that surrounds the neck of the bladder and urethra. Its function is to secrete a substance that makes up part of the seminal fluid that carries semen. When cells in the prostate start to replicate abnormally, a tumour will develop, and in many cases can become cancerous. Prostate cancer affects around 40,000 men per year in the UK accounting for 13% of all UK cancer diagnoses. Some prostate cancers can grow very slowly (known as low risk prostate cancers) or incredibly quickly (known as aggressive). Low risk prostate cancer sufferers, on the whole, have a higher chance of recovery due to the cancer usually being contained entirely in the prostate gland. Aggressive prostate cancer has the ability to grow and spread out with the prostate at a high speed, making early diagnosis essential to beating this cancer.
Mismatch Repair Genes
In mismatch repair, enzymes remove and replace incorrectly paired nucleotides that have occurred due to replication errors. Lynch syndrome occurs when there is a defect in one of these mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. This is because the replication errors are not being corrected as normal, allowing a build-up of carcinogenic errors to accumulate much faster in the DNA. (Campbell, Reece 2008)
Pattern of Inheritance
HNPCC is an autosomal dominant condition. This means that only 1 copy of the gene fault is required to be affected. If a person with Lynch syndrome were to have children, they would have a 50% chance each time of passing the faulty gene on to their children. This pattern of inheritance can be viewed as a pedigree, like the one below.
This is typically what is expected to be seen in a Lynch syndrome family.
For this study, I was asked to look through all cases of Lynch Syndrome in the West of Scotland to find if there is a link between HNPCC and prostate cancer.
I was provided with a list of 151 families with MMR gene mutations in the West of Scotland obtained from the Family Cancer Registry Database sheets. I searched though each family’s records using the online database looking for males affected with prostate cancer. For each family I noted the type of MMR gene mutation – MLH1, MSH2, MSH6 and PMS2 – and the name and age at diagnosis of each male found to have prostate cancer.
To find this information I looked through clinical records, back-scanned documents, cancer registry documents and pedigrees.
As all personal health information is held under strict legal and ethical obligations of confidentiality, I am unable to disclose any patients’ identifiable information including name, date of birth, image, CHI number or pedigree number. I had to abide by the Data Protection Act 1998, and comply with the NHS Scotland Code of Practice on Protecting Patients Confidentiality.
A research passport was not required as I am on an NHS healthcare placement.
151 families were found to carry an MMR mutation. Out of these, 53 families showed mutations in MLH1, 59 with mutations in MSH2, 26 with mutations in MSH6, 7 with mutations in PMS2, 3 with an unconfirmed MMR mutation and 3 with no results.
Out of these families, 21 men were found to have developed prostate cancer. 8 of the 21...
Please join StudyMode to read the full document