Hereditary risk factors for the development of gastric cancer in younger patients

BACKGROUND: It is believed that the development of gastric cancer (GC) before the age of 50 has a hereditary basis. Blood group A and history of gastric cancer in first-degree relatives have been shown to be risk factors for GC. METHODS: In this case-control study, we enrolled patients with GC who were diagnosed before the age of 50. Patients who were diagnosed as having GC were selected. A total of 534 cases were found; of these, 44 diagnosed before the age of 50 were included in the case group. For the control group, 22 males and 22 females were randomly selected from the remaining subjects, who had diagnoses of GC after the age of 50. All the surviving patients and family members of the dead patients were interviewed about the history of cancer in the family and the age at which other family members developed cancer. The blood group of each subject was also obtained. RESULTS: forty-four cases under 50 years old (mean age: 36.2 years) and forty-four controls (mean age: 67.1 years) were enrolled in the study. At the time of the study, 59.1% of the study group and 50% of the control group were alive (P value = NS). In the study group, 68.1%, 13.6%, 13.6% and 4.5% had blood groups O, A, B and AB, respectively. In the control group the corresponding figures were 27.7%, 63.6%, 6.8% and 4.5%. First or second-degree relatives with cancer, including gastric (the most frequent), breast, lung, gynecological and hematological malignancies, were noted in 54.5% of the cases and 11.4% of the controls (p < 0.01). Family histories of cancer were accepted as valid provided that they were based on valid medical documents. CONCLUSIONS: It seems that the development of GC before the age of 50 is likely to be accompanied by familial susceptibility. Interestingly, our study showed a significant correlation between blood group O and the development of gastric cancer under the age of 50

Deficient mismatch repair system in patients with sporadic advanced colorectal cancer

A deficient mismatch repair system (dMMR) is present in 10–20% of patients with sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in early stage disease. Data on patients with advanced disease are scarce. Our aim was to investigate the incidence and outcome of sporadic dMMR in advanced CRC. Data were collected from a phase III study in 820 advanced CRC patients. Expression of mismatch repair proteins was examined by immunohistochemistry. In addition microsatellite instability analysis was performed and the methylation status of the MLH1 promoter was assessed. We then correlated MMR status to clinical outcome. Deficient mismatch repair was found in only 18 (3.5%) out of 515 evaluable patients, of which 13 were caused by hypermethylation of the MLH1 promoter. The median overall survival in proficient MMR (pMMR), dMMR caused by hypermethylation of the MLH1 promoter and total dMMR was 17.9 months (95% confidence interval 16.2–18.8), 7.4 months (95% CI 3.7–16.9) and 10.2 months (95% CI 5.9–19.8), respectively. The disease control rate in pMMR and dMMR patients was 83% (95% CI 79–86%) and 56% (30–80%), respectively. We conclude that dMMR is rare in patients with sporadic advanced CRC. This supports the hypothesis that dMMR tumours have a reduced metastatic potential, as is observed in dMMR patients with early stage disease. The low incidence of dMMR does not allow drawing meaningful conclusions about the outcome of treatment in these patients

Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques?

<p>Abstract</p> <p>Background</p> <p>Lynch syndrome confers increased risk for various malignancies, including colorectal cancer. Colonoscopic surveillance programs have led to reduced incidence of colorectal cancer and reduced mortality from colorectal cancer. Colonoscopy every 1–2 years beginning at age 20–25, or 10 years earlier than the first diagnosis of colorectal cancer in a family, with annual colonoscopy after age 40, is the recommended management for mutation carriers. Screening programs have reduced colon cancer mortality, but interval cancers may occur.</p> <p>Case presentation</p> <p>We describe a 48-year-old woman with Lynch syndrome who was found to have an adenoma with invasive colorectal cancer within one year after a normal colonoscopy.</p> <p>Conclusion</p> <p>Our patient illustrates two current concepts about Lynch syndrome: 1) adenomas are the cancer precursor and 2) such adenomas may be “aggressive,” in the sense that the adenoma progresses more readily and more rapidly to carcinoma in this setting compared to usual colorectal adenomas. Our patient’s resected tumor invaded only into submucosa and all lymph nodes were negative; in that sense, she represents a success for annual colonoscopic surveillance. Still, this case does raise the question of whether advanced imaging techniques are advisable for surveillance colonoscopy in these high-risk patients.</p