Microsatellite instability, mismatch repair deficiency, and colorectal cancer

Gryfe, Robert; Gallinger, Steven

doi:10.1067/msy.2001.112738

Cited by 44 publications

(34 citation statements)

References 14 publications

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“…Not all eligible subjects were interviewed because of death, refusal, and other reasons; for laboratory analyses, we were not able to obtain tissue or have MSI testing completed on all individuals. We also have a higher proportion of MSI-high cases than that found in previous studies (18,38,39), which may indicate differences in survival by molecular subtype, an outcome that has been associated with MSI-high tumor status (40,41).…”

Section: Discussioncontrasting

confidence: 48%

Estrogen Plus Progestin Use, Microsatellite Instability, and the Risk of Colorectal Cancer in Women

et al. 2007

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Current users of postmenopausal hormones (PMH) have f30% to 40% lower risk of colorectal cancer (CRC), although associations with specific types of hormones have been inconsistent. Further, it is not clear whether some tumor types have a different risk. We conducted a case-control study to examine the relationship between PMH and CRC. Cases (n = 1,004), ages 50 to 74 years, were identified from the Surveillance Epidemiology and End Results registry in Washington from 1998 to 2002; controls (n = 1,062) were randomly selected from population lists. Case tissue samples were obtained for microsatellite instability (MSI) analyses. Interviews collected risk-factor data for CRC, including detailed information on PMH. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (95% CI). Current use of any PMH was associated with a 20% reduction in CRC risk (95% CI 0.6-0.9). This reduction in risk was limited to women who had taken estrogen plus progestin (EP) preparations only (OR = 0.6, 95% CI 0.5-0.9); there was no association with estrogen-only (E alone) use (OR = 0.9, 95% CI 0.7-1.1). For women with MSI-low or MSI-stable tumors, there was a statistically significant 40% reduction in CRC risk associated with EP use (95% CI 0.4-0.9); there was no clear association with MSI-high tumors. EP use was associated with a decreased risk of CRC; however, there seemed to be no association with E alone data that are consistent with the recent Women's Health Initiative findings. Progestin may enhance the estrogenic effect of conjugated estrogen so the combination may be more biologically active in the colon than E alone. [Cancer Res 2007;67(15):7534-9]

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Section: Discussioncontrasting

confidence: 48%

Estrogen Plus Progestin Use, Microsatellite Instability, and the Risk of Colorectal Cancer in Women

et al. 2007

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“…The mutation of hMSH2 mismatch repair gene can cause wide somatic mutation and DNA replication error, which results in the increase of mutation rate of antioncogene (Gryfe and Gallinger, 2001), so as to infer that related factors are likely to down-regulate nm23 gene expression. A number of studies showed that, MMR gene defect mainly promotes tumorigenesis through the following approaches (Kolodner et al, 1995): a. by increasing the mutation frequency of cancer gene or tumor suppressor gene (Loeb, 1994); b. allowing some important functional gene to have genetic instability (Rhyu, 1996); c. promoting tumorigenesis by cell injury caused by some chemicals.…”

Section: Discussionmentioning

confidence: 99%

hMSH2 and nm23 Expression in Sporadic Colorectal Cancer and its Clinical Significance

Wu¹,

Gao²,

Wei³

2013

Asian Pacific Journal of Cancer Prevention

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Objective: To study the expression of the mismatch repair proteins hMSH2 and nm23 in sporadic colorectal cancer, determine any inter-relationship, and further investigate any clinical significance. Methods: Expression of hMSH2 and nm23 proteins was assessed in 87 colorectal cancer tissues by SP immunohistochemistry, with analysis of survival using follow-up data. Results: In the sporadic colorectal cancer tissues, nm23 protein expression appeared independent of the histological type (P > 0.05), but correlated with the invasion depth and lymphatic metastasis (P < 0.05). In contrast, hMSH2 protein expression was not significantly correlated with these clinicopathologic features (P > 0.05), although it positively correlated with that of nm23 protein in the sporadic colorectal cancers (rs=0.635, P < 0.05). Combined expression of the two was found to be related with invasion depth, lymphatic metastasis and prognosis of sporadic colorectal cancer (P < 0.05). Conclusion: nm23 protein level was related with the degree of malignancy, and could be used as an index to predict the invasion and metastasis potential. The expression of hMSH2 protein is positively correlated that of nm23 protein, and the combined expression of the two has certain guiding significance for the prognosis of sporadic colorectal cancer.

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“…Accordingly, lung cancer specimens obtained from smokers have ten times as many somatic mutations as do those from nonsmokers (Govindan et al 2012). Tumors with defects in DNA repair form another group of outliers (Gryfe and Gallinger 2001). For example, tumors with mismatch repair defects can harbor thousands of mutations, even more than lung tumors or melanomas.…”

Section: Cancer Is a Multigenic Diseasementioning

confidence: 98%

Genome-Based Multi-targeting of Cancer: Hype or Hope?

Singh

Tyagi

Raman

et al. 2014

Multi-Targeted Approach to Treatment of Cancer

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Cancer is primarily an "old-age disease" that has an "age-old" history. The overall incidence of cancer is much higher in Western countries than in Eastern countries for reasons that are not understood. Almost three million studies published to date indicate that cancer is a hyperproliferative disorder that arises from dysregulation of multiple cell signaling pathways. The cancer genome landscape indicates that approximately 140 genes and 12 cell signaling pathways drive almost all types of cancers. "Targeted therapy," a buzz word in cancer treatment for the past two decades, has provided antibodies as well as small-molecule inhibitors of ligands, receptors, kinases, proteasomes, and transcription factors. In most cases, such drugs have been highly ineffective, with overall increases in survival of only few days; furthermore, in most cases, those who need these drugs cannot afford them. Natural products, in contrast, are often more effective against cancer and are very affordable; these untargeted or multitargeted products have been used from the very beginning of human history and are the roots for almost 70 % of modern drugs. The past, present, and future of preventing and treating cancer, usually a disease of lifestyle, is discussed in this mini review.

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Microsatellite instability, mismatch repair deficiency, and colorectal cancer

Cited by 44 publications

References 14 publications

Estrogen Plus Progestin Use, Microsatellite Instability, and the Risk of Colorectal Cancer in Women

Estrogen Plus Progestin Use, Microsatellite Instability, and the Risk of Colorectal Cancer in Women

hMSH2 and nm23 Expression in Sporadic Colorectal Cancer and its Clinical Significance

Genome-Based Multi-targeting of Cancer: Hype or Hope?

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