Lancet oncol: Unknown factors significantly affect the risk of colorectal cancer in patients with Lynch syndrome

The current clinical practice guidelines for carriers of DNA mismatch repair gene pathogenic variants (Lynch syndrome) are based on the average age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of the same gene.

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Colorectal cancer

This study aims to estimate the difference in colorectal cancer penetrance among carriers of pathogenic variants of the same gene
.

To estimate the difference in colorectal cancer penetrance between carriers of pathogenic variants of the same gene

This is a retrospective cohort study that obtained data from the International Mismatch Repair Consortium, which is composed of 273 members from 122 research centers or clinics in 32 countries on six continents and is dedicated to the study of Lynch syndrome
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This analysis included families with at least three members and at least one member diagnosed as carriers of a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) that are pathogenic or possibly pathogenic variants

5585 families with Lynch syndrome from 22 countries met the criteria for this analysis
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Among them, there are not enough numbers to estimate the penetrance of Asia and South America and EPCAM variants

Cumulative risk of colorectal cancer in patients with Lynch syndrome in different groups

Cumulative risk of colorectal cancer in patients with Lynch syndrome in different groups

There is strong evidence that the existence of unknown family risk factors can change the risk of colorectal cancer in patients with Lynch syndrome (p<0.
0001)
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These familial risk factors lead to widespread heterogeneity in the risk of colorectal cancer in men and women who carry the same gene or MSH2 c.

There is strong evidence that the existence of unknown family risk factors can change the risk of colorectal cancer in patients with Lynch syndrome.

Carriers of different gene variants risk ratio of colorectal cancer

Carriers of different gene variants risk ratio of colorectal cancer

This heterogeneity is particularly obvious in MLH1 and MSH2 variant carriers, and is related to gene, gender and region.
About 7-56% of MLH1 or MSH2 variant carriers have a colorectal cancer penetrance rate of <20%, 9- The penetrance rate of colorectal cancer in 44% of carriers is >80%, and the penetrance rate of colorectal cancer in only 10-19% of carriers is 40-60%
.

This heterogeneity is particularly obvious in MLH1 and MSH2 variant carriers, and is related to gene, gender and region.
About 7-56% of MLH1 or MSH2 variant carriers have a colorectal cancer penetrance rate of <20%, 9- The penetrance rate of colorectal cancer in 44% of carriers is >80%, and the penetrance rate of colorectal cancer in only 10-19% of carriers is 40-60%

The results of the study emphasize the important role of risk correction and help to promote personalized risk assessment, so as to accurately prevent and early detect the occurrence of colorectal cancer in patients with Lynch syndrome
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Precise prevention

In short, there are still large differences in the risk of colorectal cancer among patients with Lynch syndrome and cannot be generalized
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However, although the penetrance rate of colorectal cancer in some Lynch syndrome patients is relatively low, it is still higher than that of the general population

There are still large differences in the risk of colorectal cancer among patients with Lynch syndrome, which cannot be generalized

Original source:

Original source:

The International Mismatch Repair Consortium.

Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study.
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