OBJECTIVETo assess the association of programmed cell death 1 (PDCD1) gene polymorphisms with the susceptibility and/or progression of colorectal cancer.

METHODSA hospital-based case-control study was carried out, which recruited 426 colorectal cancer patients and 500 healthy individuals. Five single nucleotide polymorphisms, namely rs36084323, rs11568821, rs2227981, rs2227982 and rs10204525, were selected for the study and genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

RESULTSThe G allele of rs36084323 under a dominant model was associated with increased risk of advanced TNM staging of colorectal cancer progression (OR=1.59, 95%CI=1.02-2.48). Haplotypes G-G-C-T-A and A-G-C-C-G of the rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525 were negatively associated with the occurrence of colorectal cancer.

CONCLUSIONThe G allele of rs36084323 is associated with increased risk of advanced TNM staging of colorectal cancer. Conversely, the incidence of colorectal cancer is negatively associated with the haplotypes G-G-C-T-A and A-G-C-C-G of rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525.

Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; ethnology ; Colorectal Neoplasms ; genetics ; pathology ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; Programmed Cell Death 1 Receptor ; genetics

BACKGROUND: The rs1520220 polymorphism in the insulin-like growth factor 1 (IGF1) gene has been reported to affect cancer susceptibly in several studies. However, the results of the relevant studies are inconsistent. We conduct a current meta-analysis to investigate the association between rs1520220 and cancer susceptibly. METHODS: Three databases (PubMed, Embase, and Web of Science) were searched for studies regarding the relationship between rs1520220 and cancer susceptibly. Odds ratios (ORs) and the related 95% confidence intervals (CIs) were employed to assess the strength of the associations. A stratified analysis was performed according to cancer type, ethnicity, and quality score, and when results were obtained from no fewer than two studies, these results were pooled. RESULTS: There was no positive association between rs1520220 and overall cancer risk. However, the analysis stratified by ethnicity revealed that rs1520220 significantly increased cancer susceptibility in Asian populations (allele model OR = 1.10, 95%Cl = 1.00-1.21, p = 0.040; homozygote model OR = 1.22, 95%Cl = 1.01-1.47, p = 0.040; dominant model OR = 1.19, 95%Cl = 1.01-1.39, p = 0.033). No significantly association was detected in Caucasian populations. The analysis stratified by cancer type suggested that rs1520220 was not associated with susceptibility to breast cancer. CONCLUSIONS The results of our meta-analysis demonstrate that the role of IGF1 rs1520220 in cancer susceptibility varies by ethnicity and cancer type and that rs1520220 increases cancer susceptibility in Asian populations.
Asian Continental Ancestry Group ; Continental Population Groups ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Insulin-Like Growth Factor I ; genetics ; Neoplasms ; ethnology ; genetics ; Odds Ratio ; Polymorphism, Single Nucleotide

OBJECTIVETo assess the association of four single nucleotide polymorphisms (SNPs) (rs12190359C>T, rs562047C>G, rs1008438G>T, and rs1043618G>C) of HSPA1A gene with the development of cervical cancer among ethnic Han Chinese from Yunnan.

METHODSOne hundred and thirty patients with CIN III, 444 patients with cervical cancer, and 548 healthy individuals were recruited, and the genotypes of the above SNPs were determined with a Taqman assay. Haplotypes were constructed, and their association with the development of cervical cancer was analyzed.

RESULTSThe frequencies of G and T alleles of rs1008438G>T were significant different between the CIN III and control groups, as well as between the cancer and control groups (P=0.022 and P=0.030, respectively). There was a significant difference in genotypic frequency of rs1008438G>T between the CIN III and control groups (P=0.047). The allelic and genotypic frequencies of rs12190359C>T, rs562047C>G, and rs1043618G>C did not significantly differ between the CIN III, cervical cancer and control groups (P> 0.05). The frequencies of haplotypes formed by rs562047C>G, rs1008438G>T and rs1043618G>C also did not significantly differ between the CIN III, cancer and control groups (P> 0.05).

CONCLUSIONThe G allele of rs1008438G>T may be a protective factor for cervical cancer among ethnic Han Chinese from Yunnan.

China ; ethnology ; Female ; Genetic Predisposition to Disease ; Genotype ; HSP70 Heat-Shock Proteins ; genetics ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Uterine Cervical Neoplasms ; etiology ; genetics

OBJECTIVETo investigate the knowledge and willingness of breast cancers patients from Shanghai for genetic counseling and gene testing.

METHODSA total of 428 patients filled out the questionnaire and the data was statistically analyzed.

RESULTSMost of the patients were unaware of genetic counseling and gene testing. But after a brief introduction, a majority of them were willing to accept genetic counseling and recommend their family members to participate. The willingness was education- and age-related. When told that gene testing may benefit themselves, 92.1% of the patients were willing to be tested. However, when told that gene testing may only benefit their family, only 33.9% of the patients were willing to join the testing. The acceptance was also age-, education- and family income-related. The difference was statistically significant. Moreover, the willingness ratio to participate the gene testing was lower than expected. Overall, 74.1% of the patients were willing to accept cheaper preliminary gene screening, whilst only 19.2% were willing to accept genetic testing of higher price. Despite of being told that testing results will be maintained as confidential, still 43.2% worried about adverse effects. Such patients tended to younger, from low-income families, with a family history of associated cancers, or personal history of other cancers. The difference was statistically significant.

CONCLUSIONThe majorities of patients do not know but are willing to accept genetic counseling and gene testing and recommend their family to participate. Lack of genetic knowledge, cost for the testing and concerns about discrimination are the obstacles for patients to participate in genetic counseling and gene testing. To spread the knowledge about breast cancer and establish a follow-up screening system for high-risk population may improve the tertiary prevention for breast cancer.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; statistics & numerical data ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Breast Neoplasms ; diagnosis ; ethnology ; genetics ; Chi-Square Distribution ; China ; Educational Status ; Female ; Genetic Counseling ; Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Social Class

Accumulating studies explored the clinicopathologic and prognostic value of programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC), but the results were controversial. We therefore conducted a meta-analysis to evaluate the predictive role of PD-L1 in NSCLC patients. We systematically collected relevant studies from PubMed, Embase, Web of Science and China National Knowledge Infrastructure. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), and odd ratios (ORs) with 95% CIs for clinicopathologic factors were calculated. A total of 15 studies involving 3605 patients were included in this meta-analysis. The results showed no prognostic role of PD-L1 in the whole patients (HR=1.60, 95% CI: 0.88-2.89, P=0.123). Subgroup analysis showed that PD-L1 was associated with decreased OS in Asian patients (HR=2.00, 95% CI: 1.55-2.57, P<0.001). Among all the clinicopathologic factors, PD-L1 overexpression was significantly in relevance with poor tumor cell differentiation (HR=1.84, 95% CI: 1.49-2.28, P<0.001), late stage (HR=1.21, 95% CI: 1.02-1.43, P=0.026) and anaplastic lymphoma kinase (ALK) translocation (HR=2.63, 95% CI: 1.08-6.40, P=0.034), but not with other factors. In conclusion, our meta-analysis demonstrated that PD-L1 has a prognostic role in Asian patients with NSCLC.
Asian Continental Ancestry Group ; B7-H1 Antigen ; genetics ; metabolism ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; ethnology ; genetics ; mortality ; European Continental Ancestry Group ; Humans ; Lung Neoplasms ; diagnosis ; ethnology ; genetics ; mortality ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Protein Transport ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism

INTRODUCTIONThe Singapore Polyposis Registry (SPR) was established in 1989 in Singapore General Hospital (SGH). The aims were to provide a central registry service to facilitate identification, surveillance and management of families and individuals at high risk of colorectal cancer.

MATERIALS AND METHODSThis is a review of published literature in the department.

RESULTSThe registry currently has 253 families with several genetic conditions-93 familial adenomatous polyposis (FAP) families, 138 Amsterdam-criteria positive presumed Lynch syndrome (LS) families, 12 families with Peutz Jeghers syndrome, 2 families with Cowden's syndrome, and 8 families with hereditary mixed polyposis syndrome (HMPS). There are also 169 families with a strong family history of colorectal cancer but no abnormal genes yet identified. In FAP, a diagnostic tool developed has allowed a 94% local APC germline detection rate in FAP families. Knowledge obtained studying the phenotype of FAP patients has allowed better choice of surgery between ileal pouch anal anastomosis (IPAA) against an ileal-rectal anastomosis (IRA). In LS, our review has noted a highly heterogenous mutational spectrum and novel variants made up 46.7% (28/60) of all variants identified in this cohort. This may suggest that our Southeast Asian ethnic groups have distinct mutational variants from Western populations. Pathogenic mutations were only confined to MLH1 and MSH2, and identified in 28.8% of families.

CONCLUSIONThe impact of predictive gene testing for hereditary cancer risk in clinical practice has allowed evolution of care. Risk-reducing surgery and aggressive surveillance allows reduction in morbidity and mortality of patients. The SPR will continue to grow and improve outcomes in hereditary colorectal cancer patients and families.

Adaptor Proteins, Signal Transducing ; genetics ; Colorectal Neoplasms ; diagnosis ; ethnology ; genetics ; surgery ; Disease Management ; Female ; Genetic Testing ; methods ; Humans ; Male ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; Mutation ; Neoplastic Syndromes, Hereditary ; classification ; diagnosis ; ethnology ; genetics ; surgery ; Nuclear Proteins ; genetics ; Registries ; statistics & numerical data ; Singapore ; epidemiology

Many studies have reported the relationship between CXCL12 G801A polymorphism and cancer risk, with conflicting results. In this study, we tried to clarify the possibility that this polymorphism may increase cancer risk by conducting an updated meta-analysis. PubMed and EMbase were searched for case-control studies regarding the association of the gene polymorphism and cancer risk. Data were extracted and odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Heterogeneity among articles and publication bias was also assessed. Significantly increased risk for cancer was found (A vs. G: OR=1.26, 95% CI=1.13-1.40, P<0.01; AA+AG vs. GG: OR=1.33, 95% CI=1.16-1.52, P<0.01). In subgroup analysis, statistically elevated cancer risk was found in both Asian and Caucasian populations (for Asian, AA+AG vs. GG: OR=1.74, 95% CI=1.22-2.47, P<0.01; for Caucasian, AA+AG vs. GG: OR=1.24, 95% CI=1.09-1.42, P<0.01). Our result indicated that CXCL12 G801A polymorphism is a risk factor for cancer. To validate the finding, further large-size case-control studies are warranted.
Asian Continental Ancestry Group ; genetics ; Chemokine CXCL12 ; genetics ; European Continental Ancestry Group ; genetics ; Genetic Predisposition to Disease ; Humans ; Neoplasms ; ethnology ; genetics ; pathology ; Odds Ratio ; Polymorphism, Single Nucleotide

OBJECTIVETo evaluate the role of germline mutations of TP53 gene among a Chinese population with high risk for breast cancer.

METHODSA total of 81 BRCA-negative breast cancer probands from cancer families were analyzed using targeted capture and next-generation sequencing. Candidate mutations were verified with Sanger sequencing. Co-segregation analyses were carried out to explore the likely pathogenicity of the mutation.

RESULTSOf the 81 BRCA-negative patients, 3 exonic mutations in the TP53 gene were identified in 3 breast cancer patients. Of these, 2 mutations were previously reported and 1 was novel. One family with TP53 mutation has met the criteria for Li-Fraumeni syndrome (LFS) and accounted for 9.1% of all families who fulfilled the diagnostic criteria for LFS. Two of the carriers were diagnosed with breast cancer under the age of 30, and have accounted for 11.8% (2/17) of all very young (≤30 years) breast cancer patients in our study.

CONCLUSIONThe TP53 germline mutation is more common in Chinese population with a high risk for breast cancer than previously thought. TP53 gene mutation screening should be considered particularly for patients with a family history of LFS and very young age of onset.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; China ; DNA Mutational Analysis ; Exons ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Germ-Line Mutation ; Heterozygote ; Humans ; Li-Fraumeni Syndrome ; ethnology ; genetics ; Male ; Middle Aged ; Pedigree ; Risk Factors ; Tumor Suppressor Protein p53 ; genetics ; Young Adult

PURPOSE: Dermatofibrosarcoma protuberans (DFSP) carries a translocation resulting in the collagen type I alpha 1 (COL1A1)-platelet-derived growth factor beta (PDGFB) fusion gene, which is responsible for PDGFB activation. The purpose of this study is to evaluate the clinicopathological, genetic, and therapeutic features of DFSP in Korean patients. MATERIALS AND METHODS: Clinicopathological features of 37 patients with DFSP were reviewed. Multiplex reverse transcriptase-polymerase chain reaction (PCR) was carried out in 16 patients using formalin-fixed, paraffin-embedded tissues and specific primers for COL1A1 and PDGFB. RESULTS: The mean age of 37 patients was 37.4 years old. The most common tumor location was the trunk. All patients were treated primarily with surgery: 34 (91.7%) cases with Mohs micrographic surgery (MMS) and 3 (8.3%) cases with wide local excision. The median follow-up time was 33.7 months. Two patients, one in each treatment group, demonstrated local recurrence during the follow-up period. The COL1A1-PDGFB fusion gene was expressed in 14 (87.5%) cases, demonstrated by reverse transcriptase PCR analysis. No association was found among the different COL1A1-PDGFB fusion transcripts, the various histological subtypes and clinical features. CONCLUSION: Our results support the effectiveness of MMS in treating DFSP. The COL1A1-PDGFB fusion transcript was observed in 87.5% of patients. Therefore, COL1A1-PDGFB is a useful and accurate tool in diagnosing DFSP in Koreans.
Adolescent ; Adult ; Asian Continental Ancestry Group/*genetics ; Collagen Type I/*genetics ; DNA Primers ; Dermatofibrosarcoma/ethnology/*genetics/*pathology/surgery ; Female ; Humans ; Male ; Middle Aged ; Mohs Surgery ; Multiplex Polymerase Chain Reaction ; Neoplasm Recurrence, Local ; Oncogene Proteins, Fusion/*genetics ; Proto-Oncogene Proteins c-sis/*genetics ; Republic of Korea ; Reverse Transcriptase Polymerase Chain Reaction ; Skin Neoplasms/ethnology/*genetics/*pathology/surgery ; Treatment Outcome

PURPOSE: Dermatofibrosarcoma protuberans (DFSP) carries a translocation resulting in the collagen type I alpha 1 (COL1A1)-platelet-derived growth factor beta (PDGFB) fusion gene, which is responsible for PDGFB activation. The purpose of this study is to evaluate the clinicopathological, genetic, and therapeutic features of DFSP in Korean patients. MATERIALS AND METHODS: Clinicopathological features of 37 patients with DFSP were reviewed. Multiplex reverse transcriptase-polymerase chain reaction (PCR) was carried out in 16 patients using formalin-fixed, paraffin-embedded tissues and specific primers for COL1A1 and PDGFB. RESULTS: The mean age of 37 patients was 37.4 years old. The most common tumor location was the trunk. All patients were treated primarily with surgery: 34 (91.7%) cases with Mohs micrographic surgery (MMS) and 3 (8.3%) cases with wide local excision. The median follow-up time was 33.7 months. Two patients, one in each treatment group, demonstrated local recurrence during the follow-up period. The COL1A1-PDGFB fusion gene was expressed in 14 (87.5%) cases, demonstrated by reverse transcriptase PCR analysis. No association was found among the different COL1A1-PDGFB fusion transcripts, the various histological subtypes and clinical features. CONCLUSION: Our results support the effectiveness of MMS in treating DFSP. The COL1A1-PDGFB fusion transcript was observed in 87.5% of patients. Therefore, COL1A1-PDGFB is a useful and accurate tool in diagnosing DFSP in Koreans.
Adolescent ; Adult ; Asian Continental Ancestry Group/*genetics ; Collagen Type I/*genetics ; DNA Primers ; Dermatofibrosarcoma/ethnology/*genetics/*pathology/surgery ; Female ; Humans ; Male ; Middle Aged ; Mohs Surgery ; Multiplex Polymerase Chain Reaction ; Neoplasm Recurrence, Local ; Oncogene Proteins, Fusion/*genetics ; Proto-Oncogene Proteins c-sis/*genetics ; Republic of Korea ; Reverse Transcriptase Polymerase Chain Reaction ; Skin Neoplasms/ethnology/*genetics/*pathology/surgery ; Treatment Outcome