Mutation of hMLH1, a gene involved in DNA mismatch repair, is responsible for some families carrying the hereditary non-polypotic colorectal cancer (HNPCC) syndrome. To establish a basis for presymptomatic diagnosis of HNPCC patients who carry germline mutations in this gene, we determined the exon-intron organization of hMLH1. The results indicated that hMLH1 consists of 19 coding exons spanning approximately 100 kb, and that exons 1-7 contain a region that is highly conserved in the MLH1 and PMS1 genes of yeast. We used PCR-SSCP analysis and DNA sequencing to examine the entire coding region of the MLH1 gene in DNAs of 34 unrelated cancer patients who belong to HNPCC pedigrees. Germline mutations were detectable in eight (24%) of these patients; four of them were missense mutations, one had occurred in an intron where it would affect splicing, and the remaining three were frameshift mutations resulting in truncation of the gene product downstream of the mutation site.

We report here the result of a screening for germ-line mutations in the adenomatous polyposis coli (APC) gene in 61 new familial adenomatous polyposis (FAP) patients as well as a summary of the results of 150 patients. Examination of the entire coding region of the APC gene, based on a ribonuclease protection assay coupled with the polymerase chain reaction (PCR), disclosed mutations that were considered to cause significant defects in the APC product in 97 of 150 unrelated FAP patients. Our findings revealed the following characteristics of the germ-line mutations of APC: 1) the great majority of the mutations were found to truncate the APC product; 2) almost all of the mutations were located within the first half of the coding region; 3) no correlation was observed between the locations of germ-line mutations and extracolonic manifestations in FAP patients; 4) more than 80% of base substitutions in the APC gene were from cytosine to other nucleotides, nearly one-third of which occurred at the GpG site. Our results provide information helpful to an understanding of the APC gene and will also contribute to presymptomatic diagnosis of members in FAP families.

The measurement of tumor markers might be useful in monitoring response and in predicting the prognosis of patients with advanced gastric cancer treated with systemic chemotherapy. Tumor markers may be used as a means of monitoring treatment in patients when in an imaging study it is difficult to assess response to chemotherapy in clinical practice. Further studies are required to confirm these findings.

No abstract

We conducted a case-control study to examine the association of Helicobacter pylori infection as a risk factor in gastric cancer in the Japanese population. Serum IgG antibodies for Helicobacter pylori were determined in 55 consecutive patients with gastric cancer and in 75 age- and sex-matched mass survey subjects and 57 age- and sex-matched cancer-free patients with conditions considered at a high risk for development of gastric cancer (precancerous condition). We examined the histology in all subjects and particular focus was placed on the extent of Helicobacter pylori-associated gastritis. The seroprevalence of Helicobacter pylori in gastric cancer patients (82%) and those with a precancerous condition (89%) was significantly higher (P < 0.005) than that in the mass survey subjects (60%). Positive relative risk associations were found for patients with gastric cancer (odds ratio, 3, with 95% confidence intervals of 1.69-5.33) and those with a precancerous condition (odds ratio, 5.66, with 95% confidence intervals 2.66-12.03). Significant differences were found when comparisons were made among the case-control groups who were H. pylori-positive and had inflammatory cell infiltration (P = 0.0127). The characteristics of Helicobacter pylori in histologically examined gastric mucosa showed differences between Helicobacter pylori-infected and uninfected persons in all groups. However, for none of these groups was there a significant differences between background mucosa for Helicobacter pylori-infected persons with or without gastric cancer. Helicobacter pylori seroprevalence is strongly associated with an increased risk of gastric cancer and with a precancerous condition; histological investigation did not define additional factors that might be associated with increased cancer risk.