The transforming growth factor (TGF)-β is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF-β receptor type I (TGFβR1) may be a modifier of cancer risk by constitutively decreasing the TGF-β inhibitory signals during early tumorigenesis and increasing the TGF-β signals in tumor progression. In this study, we hypothesized that genetic variants of TGFBR1 may influence the risk of gastric cancer. We conducted a two-stage case-control study of gastric cancer, including 650 cases and 683 controls in the first stage and 484 cases and 348 controls in the second stage, and genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene. In the first stage, two SNPs rs6478974 and rs10512263 were found to be potentially associated with risk of gastric cancer (P=3.35×10(-3) for rs6478974 AT vs. TT and P=0.033 for rs10512263 CT vs. TT), which were further confirmed in the second stage with similar effects (P=0.144 and 0.049, respectively). After combining the two stages, we found that these two SNPs were associated with a significantly increased risk of gastric cancer in dominant models [adjusted odds ratio (OR)=1.36, 95% confidence interval (CI): 1.14-1.63 for rs6478974 AT/AA vs. TT; adjusted OR=1.26, 95% CI: 1.05-1.50 for rs10512263 CT/CC vs. TT] or additive model (adjusted OR=1.23, 95% CI: 1.08-1.40 for rs6478974). These findings indicate that TGFBR1 polymorphisms may be implicated with the development of gastric cancer in Han-Chinese population.

The transforming growth factor (TGF)-β is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF-β receptor type I (TGFβR1) may be a modifier of cancer risk by constitutively decreasing the TGF-β inhibitory signals during early tumorigenesis and increasing the TGF-β signals in tumor progression. In this study, we hypothesized that genetic variants of TGFBR1 may influence the risk of gastric cancer. We conducted a two-stage case-control study of gastric cancer, including 650 cases and 683 controls in the first stage and 484 cases and 348 controls in the second stage, and genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene. In the first stage, two SNPs rs6478974 and rs10512263 were found to be potentially associated with risk of gastric cancer (P=3.35×10(-3) for rs6478974 AT vs. TT and P=0.033 for rs10512263 CT vs. TT), which were further confirmed in the second stage with similar effects (P=0.144 and 0.049, respectively). After combining the two stages, we found that these two SNPs were associated with a significantly increased risk of gastric cancer in dominant models [adjusted odds ratio (OR)=1.36, 95% confidence interval (CI): 1.14-1.63 for rs6478974 AT/AA vs. TT; adjusted OR=1.26, 95% CI: 1.05-1.50 for rs10512263 CT/CC vs. TT] or additive model (adjusted OR=1.23, 95% CI: 1.08-1.40 for rs6478974). These findings indicate that TGFBR1 polymorphisms may be implicated with the development of gastric cancer in Han-Chinese population.

Lynch syndrome is the most common form of hereditary colorectal cancer (CRC). This review covers the cardinal features of Lynch syndrome with particular emphasis upon its diagnostic criteria, molecular genetics, natural history, genetic counseling, surveillance and management. Considerable attention has been given to the etiologic role of mismatch repair (MMR) genes as well as low penetrance alleles and modifier genes. The American founder mutation, a deletion of exons 1-6 of MSH2, is discussed in some detail, owing to its high frequency in the US (19 000-30 000 carriers). Genetic counseling is essential prior to patients' undergoing DNA testing and again when receiving their test results. Families with a lower incidence of CRC and extracolonic cancers, in the face of being positive for Amsterdam I criteria but who do not have MMR deficiency by tumor testing, are probably not Lynch syndrome, and thereby should preferably be designated as familial CRC of undetermined type. Patients who are either noncompliant or poorly compliant with colonoscopy, and who are MMR mutation positive, may be candidates for prophylactic colectomy, while MMR mutation-positive women who are noncompliant with gynecologic surveillance may be candidates for prophylactic hysterectomy and bilateral salpingo-oophorectomy.