Lynch syndrome is linked to germline mutations in mismatch repair genes.
Dr Timm Goecke and colleagues from Germany analyzed the genotype-phenotype correlations in the largest cohort so far reported.
Following standard algorithms, the research team identified 281 of 574 unrelated families with deleterious germline mutations.
The team found 124 had germline mutations in MLH1, and MSH2 mutations occurred in 157 patients.
A total of 988 patients with 1381 cancers were included in this analysis.
The researchers identified 181 and 259 individuals with proven or obligatory and 254 and 294 with assumed MLH1 and MSH2 mutations, respectively.
Age at diagnosis was younger both in regard to first cancer and to first colorectal cancer in MLH1 versus MSH2 mutation carriers.
| Male MLH1 mutation carriers require colonoscopy beginning at age 20|
|Journal of Clinical Oncology|
The team noted that in both groups, rectal cancers were remarkably frequent.
The time span between first and second colorectal cancer was smaller if the first primary occurred left sided.
The researchers observed that gastric cancer was the third most frequent malignancy occurring without a similarly affected relative in most cases.
All prostate cancers occurred in MSH2 mutation carriers.
Dr Goecke's team concludes, “The proportion of rectal cancers and shorter time span to metachronous cancers indicates the need for a defined treatment strategy for primary rectal cancers in hereditary nonpolyposis colorectal cancer patients.”
“Male MLH1 mutation carriers require earlier colonoscopy beginning at age 20 years.”
“We propose regular gastric surveillance starting at age 35 years, regardless of the familial occurrence of this cancer.”
“The association of prostate cancer with MSH2 mutations should be taken into consideration both for clinical and genetic counseling practice.”