In inherited medical conditions, anticipation refers to situations where children develop inherited diseases earlier than their parents. Anticipation appears to be at work in Lynch syndrome with children being diagnosed with cancer an average of 10 years earlier than their affected parent.
Danish researchers reviewed records of more than 400 people with Lynch associated cancers in families in the Danish HNPCC registry. There were 290 parent-child pairs. Two-thirds of the cancers in the entire group were colon or rectal, the rest cancers linked to Lynch syndrome.
Using a simple statistical method, the average difference between the age of cancer diagnosis of a parent and the child was 9.84 years. When the first cancer in both parent and child was colorectal, the children were diagnosed 10.85 years earlier than their parent.
There was little difference in time gaps for various mutated genes — MLH1, MSH2, or MSH6. It also made no difference if the parent was father or mother.
Only 24 individuals in the registry had colorectal cancer diagnosed during a surveillance colonoscopy. All the rest had cancer diagnosed because of symptoms. When surveillance diagnoses were excluded from calculations, there was still a difference of 9.54 years.
Lynch syndrome (also referred to as HNPCC or hereditary nonpolyposis colon cancer) is caused by inherited defects in DNA mismatch repair genes. People who carry one of these mutations have a greatly increased lifetime risk of both colorectal and uterine cancer (80 percent and 50 percent, respectively). They also are at risk for other associated cancers including ovarian, gastric, kidney, small intestine, and brain.
Mef Nilbert M.D., Ph.D. and colleagues in Denmark concluded,
The effect from anticipation demonstrated in this large, population-based Lynch syndrome cohort underscores the need to initiate surveillance programs at young age. It should also stimulate research into the genetic mechanisms that determine age at onset and whether the genetic instability that characterizes Lynch syndrome can be linked to anticipation.
SOURCE: Nilbert et al., Journal of Clinical Oncology, Volume 27, Number 3, January 20, 2009.