Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma

Abstract

The JCCA are suitable for selecting cases to analyze for gene mutations, but the JCCB are not useful for the clinical setting. The authors suggest that an age at onset younger than 50 years is also important for screening. Analyzing TGF beta RII mutations and immunohistochemical staining of hMLH1 or hMSH2 for cases with MSI phenotype are useful for selecting cases who should be tested for germline mutations.

Lower prevalence of Lynch syndrome in colorectal cancer patients in a Japanese hospital-based population

“…Even if screening was extended to patients older than 60 years of age, the prevalence of LS might be lower than expected in Japan, compared with a reported prevalence of LS of 0.5-13 % among CRC patients in Western countries [3,10,11]. In Japan, Furukawa et al [12] reported that mutations in MLH1 or MSH2 were identified in 8 These results suggested that the prevalence of LS differs depending on the country, or even the region within the country. Further investigation of the prevalence of LS according to the region will be important.…”

The utility of immunohistochemical detection of DNA mismatch repair gene proteins

“…As summarized in Table 4, the sensitivity and specificity of IHC in predicting germline mutations in this group appear less favorable than that in consecutive or sporadic series, although the studies in this group are almost invariably limited by small sample sizes (Table 3) [14,18,21,23,25,41,51,52,54,55,61]. We have recently analyzed the performance of IHC in predicting MLH1 and MSH2 germline mutations in a group of 110 patients with strong family histories of colorectal cancer (data to be published) and found that IHC had an overall sensitivity of 78% in identifying tumors that had a disease-causing germline mutation in either one of these two genes.…”

“…These factors may at least in part be the reasons that MSI status has not been consistently in perfect match with stringent Amsterdam criteria [21], mutational status [39,51,52], or the status of MMR gene promoter hypermethylation [33].…”

“…Major factors affecting MSI testing include: (1) the markers used (some studies used the NCI-suggested set of five markers [10,23,25,31]; others used more [11,13,21,52] or less [12] markers); (2) the definition for MSI-H (some used 30% of the markers positive as the cutoff for MSI-H [10,11,13,23,31,52], others used 40% [21]; still others relied solely on the status of BAT-25 and/or BAT-40 [12] or BAT-26 [27]); (3) the type of tissue used (fresh frozen tissue [21,35,62] or paraffin-embedded tissue [27,52] or a combination of both [10,11,12,13]); and (4) the precision involved in tissue dissection [10]. These factors may at least in part be the reasons that MSI status has not been consistently in perfect match with stringent Amsterdam criteria [21], mutational status [39,51,52], or the status of MMR gene promoter hypermethylation [33].…”

Awareness of Genetic Testing for Increased Cancer Risk in the Year 2000 National Health Interview Survey

“…For major adult cancers, such as breast and colorectal cancers, this percentage may be 1–2% or less [11, 12]due to the low population frequency of known inherited susceptibility mutations [13, 14]. Although overall population prevalence is low [15], numerous studies indicate that cancer susceptibility mutations occur in diverse populations and demographic subgroups [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39]. Thus risk assessment, genetic counseling, and testing [40]may benefit individuals across a range of age, gender, and race/ethnic subgroups.…”