Zheng Shu

Hereditary Colorectal Cancer in China

The purpose of this article is to review basic research as well as clinical studies on Chinese hereditary colorectal cancer. Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) accounts for 2.2% of all colorectal cancer, and Chinese criteria for suspected HNPCC have been developed. Germline mutations as well as large genomic rearrangements of mismatch repair (MMR) genes are responsible for this syndrome. Gastric cancer is the second most common cancer in Chinese HNPCC patients. Contrary to sporadic colorectal cancer in the Chinese population, HNPCC does not typically present with rectal cancer. Incidence of familial adenomatous polyposis (FAP) in China is approximately 1.5/100,000. Polyps in Chinese FAP patients can emerge as early as 16 months old, but malignant transformation usually occurs in the third and fourth decade. Total resection of the colon and rectum is necessary in FAP patients. For unresectable duodenal polyps, chemopreventive agents may be used.

Discussion on the use of taxanes for treatment of breast cancers in BRCA1 mutations carriers

BRCA1-associated cancers differ from non-hereditary cancers for many factors, including somatic mutation. It can be a subject of discussion that the natural history and response to treatment also may differ between the hereditary and sporadic subgroups. Three frequent BRCA1 mutations (5382insC, 4153delA, C61G) in the Baltic countries (Lithuania, Latvia, Byelorussia and Poland) open a way for the chip test to select a subgroup from women with breast cancer. These women with BRCA1 breast cancer have a chance to get adequate treatment, including neo-adjuvant chemotherapy. So far many retrospective studies of survival, that used the same gold standard treatment for women with BRCA1 breast cancer and for women without a mutation, have not found a difference between these groups. Some studies show a worse survival result in women with a BRCA1 mutation than women without the mutation.

Abstract A13: Applied the proteomics characteristics to detect the inherited colorectal adenomas

Introduction: Current study found that about one-third of the incidence of colorectal cancer have genetic related. Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) is the most common hereditary colorectal cancer type, each account 5% of the total colorectal cancers and about 1%. But addition to the two and several other more rare hereditary colorectal cancer, 20-25% of colorectal cancer have a clear cancer family history. The causal relationship of this genetic susceptibility population is not yet clear, but the diagnostic and intervention of this genetic susceptibility population is very important. High risk of genetic susceptibility screening, early detection, and early intervention, blocking susceptibility factor in colorectal cancer especially in colorectal adenoma, is an important way to improve the overall level of diagnosis and treatment. By comparing the proteomic difference of the patients with family history colorectal adenomas and no family history sporadic colorectal adenomas, we aim to find new markers to screen high-risk genetic susceptible populations, as a complement to the clinical diagnostic criteria of dependence on family history. Materials and Methods: A total of 90 serum samples were analyzed in this study, including 30 patients with family history colorectal adenomas, 30 no family history sporadic colorectal adenomas, and 30 healthy individuals. All samples were sex and age matched. Weak Cation Exchange magnetic beads kits were used to fractionate serum samples according to the manufactures protocols. After binding and washing, the bound proteins and peptides were eluted from the magnetic beads and mixed with matrix and spotted on to targets. Protein profiles were generated using microflex MALDI-TOF MS (Bruker Daltonics). The protein profiles were then analyzed using bioinformatics tool Zhejiang University - ProteinChip Data Analysis System software to analyze the proteomic fingerprints and find the biomarkers. Results: The pattern to separate the patients with family history colorectal adenomas and sporadic colorectal adenomas by bioinformatics was constructed, which had a specificity of 93.3% and sensitivity of 100%, respectively. The model was comprised of 6 potential biomarkers with m/z of 4644, 2218, 2082, 2071, 4615 and 2210Da, respectively. The peak, 2218, 2082, 2071 and 2210Da, was Significantly (p<0.01) highly expressed in family history colorectal adenomas compared to which in no family history patients; and the other 2 peaks were weakly expressed in family history colorectal adenomas. In order to confirm the correlation of these protein markers and the family history colorectal adenomas, the family history colorectal adenomas group is also compared to the healthy individuals. Significantly highly expressed in family history colorectal adenomas also was found in The peak, 2218, 2082, 2071 and 2210Da compared to which in healthy individuals, and the other 2 biomarkers 4644, 4615 also appeared to be expressed in an opposite way. Conclusions: Applying the proteomics approach, we found 6 peaks which differently express in patients with family history colorectal adenomas compare to sporadic colorectal adenomas and healthy individuals. In addition to the gene level detection, these proteins maybe are new colorectal cancer genetic susceptibility biomarkers, which can help to apply to screen high-risk genetic susceptible populations. Citation Format: Yu Jiekai, Huang Yanqin, Lin Chen, Yuan Ying, Zheng Shu. Applied the proteomics characteristics to detect the inherited colorectal adenomas. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A13.