BACKGROUND: Lung cancer is the main cause of cancer-related death globally. Single nucleotide polymorphism (SNP) is one of the important factors leading to the occurrence of lung cancer, but its mechanism has not been elucidated. This study intends to investigate the relationship between SNPs of CDH1, FANCB, APC genes and lung cancer genetic susceptibility. METHODS: The case-control study design was used. We collected blood samples from 270 lung cancer cases in the Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, as well as blood samples from 445 healthy volunteers as controls, and extracted genomic DNA for genotyping using the Taqman® SNP genotyping kit. The distribution of three SNP loci of CDH1 gene rs201141645, FANCB gene rs754552650 and APC gene rs149353082 in Chinese population was analyzed. Chi-square test and Logistic regression were used to analyze the relationship between different genotypes and the risk of lung cancer. RESULTS: The distribution frequencies of AA, A/G and GG genotypes at rs754552650 of FANCB gene in the control group were 27.2%, 52.6% and 20.2%, respectively. The distribution frequencies of AA and A/G genotypes were 93.7% and 6.3% in the case group, respectively, and no GG genotype was detected. The A/G genotype of the rs754552650 locus of the FANCB gene was significantly different between the case group and the control group. Compared with the carriers of AA genotype, the individuals with FANCB rs754552650 A/G genotype had a lower risk of lung cancer (OR=0.035, 95%CI: 0.020-0.062, P<0.001). CDH1 gene rs201141645 A/C and CC genotypes only existed in the control group. In addition, only 1 sample was found to have APC rs149353082 genotype in the case group. CONCLUSIONS In the Chinese population, the lung cancer risk of the individuals with FANCB rs754552650 A/G genotype was significantly decreased.
Antigens, CD/genetics* ; Cadherins/genetics* ; Case-Control Studies ; China ; Fanconi Anemia Complementation Group Proteins/genetics* ; Gene Frequency ; Genes, APC ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide

OBJECTIVE: To explore the genetic basis for a pedigree affected with familial adenomatous polyposis (FAP). METHODS: The proband, with recurrence of blood in the stool, was diagnosed with FAP by endoscopy, pathological examination and a family history. She was subjected to next generation sequencing to detect genetic variant. Suspected variant was verified by Sanger sequencing of members from her pedigree. RESULTS: The proband, her mother and brother were found to carry a heterozygous c.532-1G>A variant of the APC gene, which may lead to aberrant splicing of mRNA resulting in a truncated protein, which may lose its normal function and promote the tumorigenesis. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.532-1G>A variant of APC gene was predicted to be pathogenic(PVS1+PP1+PP4+PP5). CONCLUSION The c.532-1G>A variant of the APC gene probably underlay the pathogenesis of FAP in this pedigree.
Adenomatous Polyposis Coli/genetics* ; Adenomatous Polyposis Coli Protein/genetics* ; Female ; Genes, APC ; Humans ; Male ; Neoplasm Recurrence, Local ; Pedigree

Cribriform-morular variant papillary thyroid carcinoma (CMV-PTC) is a rare cancer that may arise in patients with familial adenomatous polyposis (FAP). Adenomatous polyposis coli (APC) gene mutation is associated with FAP, which is known as a premalignant lesion of colon cancer. In this report, we report a 16 years old patient of CMV-PTC comorbid with FAP, which was related with a new type of APC gene mutation.
Adenomatous Polyposis Coli ; Colonic Neoplasms ; Genes, APC ; Humans ; Thyroid Gland ; Thyroid Neoplasms

Familial adenomatous polyposis (FAP) is one of the most common hereditary colorectal cancers. Its intestinal and extra-intestinal manifestations are correlated with mutation sties of the APC gene. Potential gene modulation sites in patients who have typical clinical manifestations but with unidentified APC mutations are also discussed, which included MUTYH gene, AXIN gene and certain epigenetic changes. With the generalization of Precision Medicine, to offer individualized treatment and surveillance strategy based on the genotype-phenotype correlation will be of great value for FAP patients. This review focuses on the research advance in genotype - phenotype correlation studies of FAP patients.
Adenomatous Polyposis Coli ; genetics ; Axin Protein ; genetics ; DNA Glycosylases ; genetics ; Genes, APC ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Mutation ; beta Catenin ; genetics

OBJECTIVETo explore the clinical features and molecular mutation of early-onset familial adenomatous polyposis(FAP) in childhood.

METHODThe clinical features, endoscopic findings, pathology and therapeutic effect of sulindac during 11 years follow-up in a child with FAP were retrospectively reviewed . Adenomatous polyposis coli (APC) gene mutation analysis was performed by PCR and first generation sequencing.

RESULTThis 6-year-old girl was admitted for intermittent bloody stool during the last one and a half years. Colonoscopy showed hundreds of polyps in the rectum and colon. Pathological examination revealed tubular adenomas with high grade dysplasia. During the follow-up period of 11 years, the child presented intermittent mucous bloody stool. Endoscopy showed the number of polyps in colon and rectum increased to thousands, and found multiple polyps in gastric fundus and body.She was treated with sulindac at the age of 13. Then the number of polyps and the grade of pathology showed a slight improvement and no carcinoma was seen on biopsy. She has not accepted surgery until now. Gene sequencing of this child revealed 5 bp deletion at codon 1,309 of exon 15 (c.3927_3931delAAAGA) of tumor suppressor gene, whereas none of her parents had the same mutation. And no polyps were found on her parents colonoscopy.

CONCLUSIONThis child with FAP had an early onset of this disease, and clinical conditions were exacerbated with age. Sulindac was partially effective in controlling size and number of polyps. The site of mutation in this case was consistent with classic FAP, and without family history, the mutation may be a sporadic one.

Adenomatous Polyposis Coli ; Biopsy ; Child ; Colonoscopy ; Female ; Gastrointestinal Hemorrhage ; Genes, APC ; Humans ; Mutation ; Polymerase Chain Reaction ; Rectum ; Retrospective Studies

BACKGROUND/AIMS: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. METHODS: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. RESULTS: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 high-grade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). CONCLUSIONS: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms.
Aged ; Basic Helix-Loop-Helix Transcription Factors/genetics ; DNA Methylation ; Female ; Gastrectomy/methods ; Genes, APC/physiology ; Genes, mos/genetics ; Humans ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasms, Second Primary/epidemiology/*genetics/pathology ; Proportional Hazards Models ; Risk Factors ; Stomach Neoplasms/genetics/*pathology/surgery ; Thrombomodulin/genetics

Familial adenomatous polyposis (FAP) is a precancerous clinical entity, which is characterized by the development of numerous adenomatous polyps throughout the colon and rectum. The majority of FAP are associated with mutations of the adenomatous polyposis coli (APC) gene. Until now, more than 1,000 different APC mutations have been reported and some mutations express attenuated phenotypes which are milder forms with 10~100 colorectal polyps. We identified a novel mutation of APC gene which expressed an attenuated FAP but caused large gastroduodenal tubular adenomas requiring repeated endoscopic resections. A 16-year-old girl was referred to Incheon St. Mary's Hospital for evaluation of gastric polyposis. Initial esophagogastroduodenoscopy (EGD) showed numerous gastric polyps in the fundus and upper body and a few polyps in the duodenum. Pathologic examination confirmed gastric polyps as fundic gland polyps and duodenal polyps as tubular adenomas. Only a few colonic polyps of 2 to 5 mm in size were found on colonoscopy. Genetic analysis using polymerase chain reaction and direct sequencing revealed a novel stop codon mutation at codon 1522 in exon 16 of APC gene. At 12-month, 18-month, and 35-month follow-up EGD, large duodenal polyp and gastric polyps were removed endoscopically.
Adenoma ; Adenomatous Polyposis Coli* ; Adenomatous Polyps ; Adolescent ; Codon ; Codon, Terminator ; Colon ; Colonic Polyps ; Colonoscopy ; Duodenum ; Endoscopy, Digestive System ; Exons ; Female ; Follow-Up Studies ; Genes, APC* ; Germ-Line Mutation* ; Humans ; Incheon ; Phenotype ; Polymerase Chain Reaction ; Polyps* ; Rectum

Attenuated familial adenomatous polyposis (AFAP) is a variant of familial adenomatous polyposis with fewer than one hundred colorectal polyps and a later age of onset of the cancer. Here, we report two cases of AFAP within family members. Each patient demonstrated the same novel germ line mutation in exon 15 of the adenomatous polyposis coli (APC) gene and was successfully managed with sulindac after refusal to perform colectomy: a 23-year-old man with incidentally diagnosed gastric adenoma and fundic gland polyps underwent colonoscopy, and fewer than 100 colorectal polyps were found; a 48-year-old woman who happened to be the mother of the 23-year-old man also showed fewer than 100 colorectal polyps on colonoscopy. Genetic analysis revealed a novel frameshift mutation in exon 15 of the APC gene. The deletion of adenine-guanine with the insertion of thymine in c.3833-3834 resulted in the formation of stop codon 1,287 in both patients. The patients were treated with sulindac due to their refusal to undergo colectomy. The annual follow-up upper endoscopy and colonoscopy in the following 2 years revealed significant regression of the colorectal polyps in both patients.
Adenoma ; Adenomatous Polyposis Coli ; Age of Onset ; Codon, Terminator ; Colectomy ; Colonoscopy ; Disulfiram ; Endoscopy ; Exons ; Female ; Follow-Up Studies ; Frameshift Mutation ; Genes, APC ; Germ-Line Mutation ; Humans ; Mothers ; Polyps ; Sulindac ; Thymine

OBJECTIVETo study the expression of Wnt5a gene mRNA and Wnt5a, APC, β-catenin proteins in human colorectal adenocarcinoma (CRC) and explore its clinical significance.

METHODSWnt5a mRNA level was measured in 30 patients with CRC and paired non-tumor tissues by real-time PCR. Immunohistochemical staining of Wnt5a, APC, β-catenin was performed in samples of 62 patients with CRC using SP system.

RESULTSThe relative expression level of Wnt5a mRNA in fresh CRC is 0.1232 ± 0.0140, which is significantly higher than that in adjacent colorectal mucosa (0.0497 ± 0.0074, P = 0.02). A low expression of Wnt5a protein was observed in 38 of 62 CRC. Wnt5a protein expression was closely correlated with the tumor types and the degree of tumor differentiation (P < 0.05). There was no apparent relationship with lymph node metastasis, depth of myometrial invasion and TNM stages (P > 0.05). APC protein was decreased in 38 of 62 CRC. The expression of APC was closely correlated with the tumor types (P < 0.05). There was no apparent relationship with the degree of tumor differentiation, lymph node metastasis, depth of myometrial invasion and TNM stages (P > 0.05). The expression of β-catenin was observed in cytoplasm and/or cell nuclei in 50 of 62 CRC. The positive rate of β-catenin expression was closely correlated with the degree of tumor differentiation, lymph node metastasis, depth of myometrial invasion and TNM stages (P < 0.05). There was no apparent relationship with the tumor types (P > 0.05). The expressions of Wnt5a (r = 0.271, P = 0.027) and APC (r = 0.343, P = 0.004) were correlated with that of β-catenin in CRC, respectively, but there was no correlation between the expressions of Wnt5a and APC protein (r = 0.218, P = 0.078) in the tumors.

CONCLUSIONSWnt5a, APC and β-catenin genes might be involved in the carcinogenesis and development of CRC. It is hypothesized that down-regulation of APC and Wnt5a proteins may be one of causes of ectopic expression of β-catenin in CRC.

Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; Adenomatous Polyposis Coli Protein ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; Cell Differentiation ; Colorectal Neoplasms ; metabolism ; pathology ; Down-Regulation ; Female ; Genes, APC ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Proto-Oncogene Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Wnt Proteins ; genetics ; metabolism ; Wnt-5a Protein ; beta Catenin ; metabolism

In this article, I will survey the major genetic susceptibility and somatic genetic alterations involved in gastric cancer and adenoma. These include germline and somatic genetic alterations in oncogenes, tumor suppressor genes, and apoptosis-related genes. A small proportion of gastric cancers arise as a consequence of hereditary predisposition caused by specific germline mutations in E-cadherin, mismatch repair genes, adenomatous polyposis coli, and STK11. Aberrant expression of activation induced cytidine deaminase, triggered by Helicobacter pylori infection, accumulates with genetic mutations of oncogenes and tumor suppressor genes, including p53 and CTNNB1. Inactivation of trefoil factor family 1, which is a gastric specific tumor suppressor, occurs in gastric adenomas and cancers. Ectopic expression of CDX2 leads to intestinal metaplasia and defective Cdx2 expression accelerates the transformation of metaplastic cells to gastric cancer. Genetic alterations of p53 and genes related to Wnt signaling pathway and microsatellite instability occur early in the development of gastric carcinoma, indicating that detection of certain genetic alterations in adenomas may be indicative of malignant transformation. In addition, inactivation of apoptosis-inducing gene caused by mutations may be an escaping mechanism against apoptotic cell death and contribute to the progression of gastric cancer. Although the results of many studies are contradictory with one another, genetic alterations in oncogenes and tumor suppressor genes are present even in gastric adenoma and increase in frequency during multistep gastric carcinogenesis. Genetic alterations described herein, and from as yet unidentified target genes in gastric cancer cells, will guide us towards more effective risk assessment, diagnosis, and treatment.
Adenoma ; Apoptosis ; Cadherins ; Cell Death ; Cytidine Deaminase ; DNA Mismatch Repair ; Genes, APC ; Genes, Tumor Suppressor ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Helicobacter pylori ; Humans ; Lotus ; Metaplasia ; Microsatellite Instability ; Oncogenes ; Peptides ; Risk Assessment ; Stomach Neoplasms ; United Nations ; Wnt Signaling Pathway