DNA mismatch repair genes and colorectal cancer

Wheeler, James M.; Bodmer, W F; Mortensen, N. J. McC.

doi:10.1136/gut.47.1.148

Cited by 161 publications

(131 citation statements)

References 91 publications

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“…The assumption was that the association between CRC and endometrial cancer was only due to HNPCC and that the risk of endometrial cancer was somewhat higher than that of CRC. 8,37 The present data on offspring CRC risk by parental CRC and endometrial cancer would also be consistent with the estimation that some 50% of familial CRC adenocarcinoma was due to HNPCC and the proportion could be even higher among those diagnosed before age 40 (Table III). When the parental CRC risk was analyzed by offspring cancer, the association to endometrial cancer was small (SIR 1.21) compared to colon and rectal adenocarcinoma (SIRs 1.96 and 1.94, Table IV), suggesting a far lower attributable proportion of HNPCC at higher age.…”

Section: 14supporting

confidence: 90%

Familial colorectal adenocarcinoma from the Swedish family-cancer database

Hemminki

2001

Int. J. Cancer

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Familial risks for colorectal (CRC) adenocarcinoma were characterized from the Swedish Family-Cancer Database covering 9.6 million individuals, whose family relationships and cancers were obtained from registered sources, not sensitive to reporting or ascertainment bias. Cancer cases were retrieved from the Swedish Cancer Registry from years 1958 -96. Standardized incidence ratios (SIRs) were calculated based on gender-, age-, period-and tumor type specific rates. A total of 4,794 and 67,925 CRCs were recorded in offspring and parents, respectively. For colon and rectal adenocarcinoma, the SIRs in offspring were 2.28 and 1.68 by parental CRC adenocarcinoma, giving attributable proportions of 6.45 and 3.31%, respectively. The SIR of CRC was over 10 when both offspring and parents were diagnosed at a young age. The risk for parental CRC adenocarcinoma was over 100 when 2 or more children were affected. The risk in siblings was also very high when a parent was affected. The familial cancer sites that associated with CRC were those typical of hereditary nonpolyposis colorectal cancer (HNPCC). This is the largest study published on familial CRC and the only one reporting specifically on adenocarcinoma. The data suggest that HNPCC is the largest single disease entity among CRCs, probably accounting for less than 50% of familial CRC. Other familial components appear heterogeneous, characterized by incomplete penetrance, recessive mode of inheritance and few associated tumor sites.

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Section: 14supporting

confidence: 90%

Familial colorectal adenocarcinoma from the Swedish family-cancer database

Hemminki

2001

Int. J. Cancer

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“…MSI + colorectal carcinoma has been associated with a more favourable clinical outcome (Chung and Rustgi, 2003) that has confounded clinical studies assessing drug efficacy among colorectal cancer patients. Compared with MMR-proficient tumours, MMR-deficient tumours (MSI + ) tend to be proximal to splenic flexure, poorly differentiated, mucinous, characterized by marked lymphocyte infiltration, and frequently large in size (Wheeler et al, 2000). MSI + was also strongly associated with a decreased likelihood of lymph node and distant organ metastases (Malesci et al, 2007).…”

Section: Mmr Defects and Human Cancermentioning

confidence: 99%

DNA mismatch repair: Molecular mechanism, cancer, and ageing

Hsieh

Yamane

2008

Mechanisms of Ageing and Development

397

359

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DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.

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“…Microsatellites are a type of DNA that consists of tandem repeats, usually between one and ®ve base pairs, repeated many times 138 39,142±148 . HNPCC is an autosomal dominantly inherited condition that accounts for approximately 5 per cent of all cases of colorectal cancer 138 .…”

Section: Microsatellite Instabilitymentioning

confidence: 99%

“…Microsatellites are a type of DNA that consists of tandem repeats, usually between one and ®ve base pairs, repeated many times 138 . Hundreds of thousands of microsatellites are found interspersed throughout the human genome and are particularly prone to errors during DNA replication.…”

Section: Microsatellite Instabilitymentioning

confidence: 99%

“…Hundreds of thousands of microsatellites are found interspersed throughout the human genome and are particularly prone to errors during DNA replication. Such errors are usually repaired by mismatch repair (MMR) proteins but, in the absence of competent MMR function, microsatellite errors accumulate 138 . When these errors are suf®ciently frequent, the term MSI or replication error positive (RER + ) is applied.…”

Section: Microsatellite Instabilitymentioning

confidence: 99%

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The colorectal adenoma–carcinoma sequence

Leslie

Carey

Pratt

et al. 2002

British Journal of Surgery

596

448

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Background: It is widely accepted that the adenoma±carcinoma sequence represents the process by which most, if not all, colorectal cancers arise. The evidence supporting this hypothesis has increased rapidly in recent years and the purpose of this article is to review this evidence critically and highlight its clinical signi®cance.Methods: Medline searches were used to identify recent key articles relating to the adenoma±carcinoma sequence. Further pertinent articles were obtained by manual scanning of the reference lists of identi®ed papers.Results: The evidence supporting the adenoma±carcinoma sequence can be classi®ed as epidemiological, clinicopathological and genetic. The most recent and largest body of data relates to molecular genetic events and their cellular effects; however, many other approaches, such as cytogenetics, molecular cytogenetics and cytometry, have also yielded valuable information.Conclusion: Recent work continues to support the adenoma±carcinoma sequence, but there is a paucity of data on the interrelationship between different genetic mutations and on the relationship between molecular and other types of genetic abnormalities. The clinical utility of the observations described has yet to be fully realized and global genetic analysis of colorectal tumours may prove to be central in rational adenoma management. IntroductionColorectal cancer is the second leading cause of cancerrelated death in the Western world; in the UK there are currently around 30 000 new cases per annum and 17 000 related deaths 1 . In recent years our understanding of the cellular and molecular events underlying the development of colorectal cancer has improved immeasurably but, despite this and advances in surgery, radiotherapy and chemotherapy, the average 5-year survival rate remains around 40 per cent 1 . One of the most important fundamental concepts in colorectal cancer to emerge in recent years has been the adenoma±carcinoma sequence, a term that describes the stepwise progression from normal to dysplastic epithelium to carcinoma associated with the accumulation of multiple clonally selected genetic alterations. This concept not only provides an excellent model to study the genesis of invasive cancer, but also affords a means of preventing colorectal cancer by endoscopic removal of precursor lesions.The appropriate management of individuals with precursor adenomatous polyps (adenomas) is of the utmost importance. It is known that after removal of such polyps 30±35 per cent of patients will have further adenomas detected at 3±4 years 2±4 and this has led to a policy of endoscopic surveillance for all adenoma-bearers 5 . However, given that approximately 40 per cent of the Western population will develop adenomas 6±8 and only 3 per cent will go on to suffer from colorectal cancer, it is clear that only a small proportion of adenomas progress to malignancy. Unfortunately, there are no reliable criteria available that can predict adenoma progression or recurrence, and the important questions of which individuals...

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DNA mismatch repair genes and colorectal cancer

Cited by 161 publications

References 91 publications

Familial colorectal adenocarcinoma from the Swedish family-cancer database

Familial colorectal adenocarcinoma from the Swedish family-cancer database

DNA mismatch repair: Molecular mechanism, cancer, and ageing

The colorectal adenoma–carcinoma sequence

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