A636P testing in Ashkenazi Jews

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome.
• Mutations in DNA mismatch repair genes, primarily MLH1 and MSH2, cause HNPCC.
• Founder mutations are significant contributors to HNPCC in specific populations.

Purpose of the Study:

• To review the literature and present personal experience with the MSH2*1906G > C (A636P) founder mutation in Ashkenazi Jews.
• To assess the prevalence and impact of the A636P mutation in Ashkenazi Jewish patients with colorectal cancer.
• To outline the initial experience with a prospective A636P genetic testing protocol.

Main Methods:

• Literature review on HNPCC and founder mutations.
• Analysis of personal data on MSH2*1906G > C (A636P) mutation testing.
• Description of a prospective genetic testing protocol for at-risk Ashkenazi Jewish individuals.

Main Results:

• The A636P mutation, while rare globally, is found in up to 7% of early-onset colorectal cancer patients in the Ashkenazi Jewish population.
• This founder mutation may account for up to one-third of HNPCC cases within this demographic.
• Initial data from a prospective testing protocol are summarized.

Conclusions:

• The MSH2 A636P founder mutation is a key genetic factor in hereditary nonpolyposis colorectal cancer among Ashkenazi Jews.
• Targeted genetic screening for the A636P mutation is valuable for early detection and risk assessment in this population.
• Further implementation and evaluation of prospective testing protocols are warranted.