Widespread predictive genetic screening of people at elevated risk of developing Lynch syndrome, a genetic disorder present in up to 4% of colorectal cancers and 5% of endometrial cancers, is life saving and cost effective, compared with current standard practice, researchers reported Nov. 18 in Cancer Prevention Research.
Lynch syndrome is a predisposition to certain cancers, prominently colorectal and endometrial cancers, caused by germline mutations in the genes that regulate DNA mismatch repair. Currently, people are tested only when presenting with cancers; if the syndrome is found to be present, predictive testing is also offered to their relatives, though uptake is low.
The study findings suggest that colorectal and endometrial cancers caused by Lynch syndrome might be better and more cheaply reduced with a broad, population-based screening strategy involving family history–based risk assessment and tests for mutations in MLH1, MSH2, MSH6, and PMS2 – genes associated with Lynch syndrome.
For their research, Tuan A. Dinh, Ph.D., of Archimedes Inc., a health care modeling firm in San Francisco, and colleagues at clinical institutions in the United States and the Netherlands employed a mathematical model using a simulation, or "virtual population," of 100,000 U.S. individuals to assess the ideal age and risk level at which predictive Lynch syndrome screening becomes cost effective.
The virtual population was constructed using data from published literature that included, among other things, population prevalence of the syndrome and of colorectal and endometrial cancers. The researchers also created a family history model of cancer validated against data on family histories of colorectal cancer in the general population and from a Lynch syndrome registry. Prices used to help determine cost effectiveness were derived from Medicare reimbursement rates.
The modeling showed that a family history–based risk assessment beginning between the ages of 25 and 35 years, followed by genetic testing of anyone with a 5% or higher risk of having the mutations, "reduced colorectal and endometrial cancer incidence in mutation carriers by approximately 12.4% and 8.8%," respectively, the investigators said (Cancer Prev. Res. 2010;4:1-13).
For a population of 100,000 individuals containing 392 mutation carriers, "this strategy increased quality adjusted life-years (QALY) by approximately 135 with an average cost-effectiveness ratio of $26,000 per QALY," Dr. Dinh and colleagues wrote, putting it on par for cost effectiveness with other cancer-prevention strategies in the general population, "such as colorectal cancer screening, cervical cancer screening, and breast cancer screening."
Genetic screening of unaffected at-risk individuals, conducted after appropriate risk assessment and followed by surveillance for colorectal and endometrial cancer, "would cost-effectively improve health outcomes. Furthermore, it offers an evidence-based justification for a shift in the clinical approach to Lynch syndrome from one that is reactive to proactive," Dr. Dinh and colleagues wrote.
The study was carried out by Archimedes Inc., a firm that produces epidemiological models using "virtual populations," under a grant from Myriad Genetics Laboratory. Neither Dr. Dinh nor his coauthors disclosed potential conflicts of interest.