Upper tract urothelial carcinoma (genetic factors: Lynch Syndrome patients)

 Blogger's Note: this research paper does not discuss a possible survival benefit in Lynch Syndrome mutation carriers; for a recent paper (posted on this blog) regarding this issue see (open access):  Reduced life expectancy seen in hereditary diseases which predispose to early-onset tumors

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Diagnosis
The most common presenting symptom for UTUC is haematuria, which may be visible or non-visible.....

Abstract

Upper tract urothelial carcinoma (UTUC) accounts for approximately 5% of all urothelial carcinoma. There are many risk factors for UTUC, including environmental and genetic risk factors, some of which are in common with bladder cancer. The gold standard surgical management of UTUC is radical nephroureterectomy (RNU) with excision of bladder cuff, which is increasingly being performed laparoscopically or robotically with various methods used for the distal ureter. There are increasing numbers of patients being treated endoscopically, with excellent oncological outcomes in low-grade disease. The use of topical BCG and chemotherapy agents has been extrapolated from bladder cancer and may be an adjunct to endoscopic management in those patients in whom it is imperative to avoid RNU. 

"Inherited genetic factors

Epidemiological data suggest that UC primarily arises through acquired rather than inherited risk factors. These acquired exposures may interact with gene modifications to modify the carcinogen load. Examples include slow or fast variants of detoxification enzymes that prolong or reduce carcinogen exposure.⁷ Furthermore, recent genome-wide association studies have identified gene polymorphisms that slightly increase disease risk when compared to the general population.^8,9 Their functional significance is currently unknown but they appear to increase the risk of bladder UC and UTUC.⁹

An exception to these acquired risks is familial UTUC that occur within the Lynch cancer syndrome. This is the commonest familiar cancer syndrome (also known as hereditary non-polyposis colon cancer (HNPCC) (Lynch Syndrome)), and up to one-third of cancers occur outside the gastrointestinal tract. UTUC is the third commonest cancer in Lynch syndrome (accounting for 5% of tumours) after colonic (63%) and endometrial (9%) tumours. In 1317 HNPCC kindreds were found to have significantly increased incidence of cancers of the renal pelvis and ureter (22-fold increase) compared to the general population.⁵ Lynch syndrome is caused by inherited mutations of one mismatch repair (MMR) gene. These encode proteins that repair DNA replication errors. Loss of MMR produces genetic instability (seen in the highly repetitive DNA microsatellite regions, termed microsatellite instability (MSI)) and carcinogenesis.^10,11 As seen in other sites with familial cancers, a proportion (10%–15%) of sporadic UTUC also have MSI as their carcinogenic mechanism. In these tumours, MMR loss occurs mostly through epigenetic means (especially DNA promoter hypermethylation).^12"

Navigate This Article

1. Top
2. Abstract
3. Introduction
4. Risk factors
5. Pathological features
6. Diagnosis
7. Prognostic factors
8. Treatment
9. Conclusions
10. Article Notes
11. Notes
12. References