OBJECTIVETo investigate the association of p53 polymorphisms with susceptibility to breast cancer in Chinese Han population.

METHODSIn this population-based case-control study, 84 cases with breast cancers and 168 controls, matched to the cases in terms of gender, habitation and age (5 years), were genotyped for codon 72, intron 3, and intron 6 polymorphisms in p53 gene by polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP) methods. The haplotype distribution was estimated and compared by EH linkage software 1. 2.

RESULTSThe distributions of age, alcohol drinking, family history of cancer in first and second relatives were not significantly different between cases and controls. There was significant association between cigarette smoking and breast cancer (chi(2)=6.455, P=0.018), the percentage of ever or current smokers was significantly higher in cases (7.1 %) than that in controls (1.2%). The distributions of allelotype and genotype of codon72, intron 3, and intron 6 were also not significantly different between cases and controls (P>0.05). No significant association was found between the risk of breast cancer and p53 polymorphisms. The genetic linkage disequilibrium existed in these three polymorphic sites in controls, and the Arg-A-G and Pro-A-G were the most common haplotypes both in cases and controls. There was no significant association of p53 haplotype with risk of breast cancer.

CONCLUSIONp53 codon72, intron 3, and intron 6 polymorphisms may not be associated with the susceptibility of breast cancer. The Arg-A-G and Pro-A-G haplotypes are the most common haplotypes in Chinese Han population.

Aged ; Breast Neoplasms ; genetics ; Case-Control Studies ; China ; ethnology ; Female ; Genes, p53 ; genetics ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; Humans ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Risk Factors

The X-ray repair cross-complementing group 1 (XRCC1) gene is believed to play an important role in base excision repair and displays genetic polymorphisms. Data on the role of XRCC1 polymorphisms in cancer susceptibility is inconsistent. In the present study, we investigated the effect of two XRCC1 polymorphisms, Arg194Trp and Arg399Gln, on breast cancer risk in a case- control study involving Turkish breast cancer patients and healthy women. Both alleles exhibited a similar distribution among cases and controls leading to lack of any significant association between the XRCC1 polymorphisms and breast cancer risk, either in homozygotes and heterozygotes or combined. The allele frequency of the codon 194 variant was very low in cases and healthy individuals (5.3 and 3.9%, respectively) compared to that of the variant 399Gln allele (39.7 and 37.4%). Our results do not support evidence for a role of the XRCC1 polymorphism in developing breast cancer.
Alleles ; Breast Neoplasms/ethnology/*genetics ; Comparative Study ; DNA-Binding Proteins/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/ethnology/*genetics ; Heterozygote ; Homozygote ; Humans ; *Polymorphism, Genetic ; Research Support, Non-U.S. Gov't ; Risk ; Turkey

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

OBJECTIVETo investigate the association of polymorphisms of CDT1 and GMNN gene, two important genes participating in DNA replication, with the risk of sporadic breast cancer.

METHODSUsing polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis (PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a case-control study of 427 breast cancer cases and 477 cancer-free controls in a Chinese population.

RESULTSNo significant association of the CDT1 838G/A and GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95% CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a significant association of CDT1 GA+AA genotypes with breast cancer risk among subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20-4.09).

CONCLUSIONThese findings suggest that the CDT1 838G/A and GMNN 387C/A polymorphisms may not play a major role in the etiology of breast cancer, but CDT1 variant may have a potential role only in genetically susceptible women.

Adult ; Asian Continental Ancestry Group ; genetics ; Breast Neoplasms ; ethnology ; genetics ; Case-Control Studies ; Cell Cycle Proteins ; genetics ; China ; Female ; Geminin ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length

OBJECTIVETo study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population.

METHODSThe known BRCA1/2 gene mutations in author's previous studies were reanalyzed by denaturing high performance liquid chromatography and DNA sequencing method in 177 patients with early onset breast cancer or affected relatives and 426 sporadic breast cancer patients from four breast cancer centers in China.

RESULTSThree cases were found with BRCA1 5589del8 mutation out of 247 hereditary-predisposing breast cancer patients (70 patients in previous study and 177 patients in current study) and 2 cases with BRCA1 5589del8 mutation out of 426 sporadic breast cancer patients. They had similar even same haplotype.

CONCLUSIONBRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.

Adult ; Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; China ; Chromatography, High Pressure Liquid ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Mutation

OBJECTIVETo investigate the association between single nucleotide polymorphisms (SNPs) of BARD1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang.

METHODSA case-control study was designed to explore the genotypes of Pro24Ser (C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene, detected by PCR-restriction fragment length polymorphism (PCR-RFLP) assay, in 144 early-onset breast cancer cases of Uygur women (≤ 40 years) and 136 cancer-free controls matched by age and ethnicity. The association between SNPs of BARD1 gene and risk of early-onset breast cancer in Uygur women was analyzed by unconditional logistic regression model.

RESULTSEarly age at menarche, late age at first pregnancy, and positive family history of cancer may be important risk factors of early-onset breast cancer in Uygur women in Xinjiang. The frequencies of genotypes of Pro24Ser (C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene showed significant differences between the cancer cases and cancer-free controls (P < 0.05). Compared with wild-type genotype Pro24Ser CC, it showed a lower incidence of early-onset breast cancer in Uygur women with variant genotypes of Pro24Ser TT (OR = 0.117, 95%CI = 0.058 - 0.236), and dominance-genotype CT+TT (OR = 0.279, 95%CI = 0.157 - 0.494), or Arg378Ser CC (OR = 0.348, 95%CI = 0.145 - 0.834) and Val507Met AA(OR = 0.359, 95%CI = 0.167 - 0.774). Furthermore, SNPS in three polymorphisms would have synergistic effects on the risk of breast cancer. In addition, the SNP-SNP interactions of dominance-genotypes (CT+TT, GC+CC and GA+AA) showed a 52.1% lower incidence of early-onset breast cancer in Uygur women (OR = 0.479, 95%CI = 0.230 - 0.995). Stratified analysis indicated that the protective effect of carrying T variant genotype (CT/TT) in Pro24Ser and carrying C variant genotype (GC/CC) in Arg378Ser were more evident in subjects with early age at menarche and negative family history of cancer. With an older menarche age, the protective effect was weaker.

CONCLUSIONSSNPs of Pro24Ser(C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene are associated with significantly decreased risk of early-onset breast cancer in Uygur women in Xinjiang. Early age at menarche and negative family history of cancer can enhance the protective effect of mutant allele.

Adult ; Age Factors ; Age of Onset ; Breast Neoplasms ; epidemiology ; genetics ; Carcinoma, Ductal, Breast ; epidemiology ; genetics ; Case-Control Studies ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Risk Factors ; Tumor Suppressor Proteins ; genetics ; Ubiquitin-Protein Ligases ; genetics

OBJECTIVETo investigate the prevalence of CHEK2 c.1100delC mutation among non-BRCA1/BRCA2 familial/early-onset breast cancer patients in Shanghai.

METHODSOne hundred and fourteen non-BRCA1/BRCA2 hereditary breast cancer patients were analyzed, among whom 76 cases had at least one first-degree relative affected with breast cancer and 38 cases were diagnosed as breast cancer below the age of 40 years without family history. The mutation genotyping of CHEK2 c.1100delC were carried out through long-range PCR amplifying of exons 10-14, and followed by amplification of exon 10 and then DNA direct sequencing.

RESULTSNo c.1100delC frame-shift mutation was identified in our studied population. One novel missense mutation 1111C>T (p.His371Tyr), located in kinase catalytic domain, was found in 3 familial breast cancer cases but no one in control group.

CONCLUSIONCHEK2 c.1100delC is rare variant for Chinese population and may not contribute to predisposition for hereditary breast cancer in Shanghai. Novel variant -1111C>T could be in association with genetic susceptibility to breast cancer. A further study is needed to confirm the results.

Adult ; Aged ; Apoptosis Regulatory Proteins ; Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; Checkpoint Kinase 2 ; China ; DNA Mutational Analysis ; Female ; Frameshift Mutation ; Genetic Predisposition to Disease ; genetics ; Humans ; Middle Aged ; Mutation, Missense ; Protein-Serine-Threonine Kinases ; genetics ; Sequence Deletion ; Young Adult

OBJECTIVEAromatase, encoded by CYP19A1, play an important role in estrogens biosynthesis from androgens. The present study is to investigate effect of R264C single nucleotide polymorphism in CYP19A1 gene on genetic susceptibility for hereditary breast cancer without BRCA1/2 mutant.

METHODSOne hundred and fourteen BRCA1/2 -negative hereditary breast cancer patients from independent families and 121 age-matched healthy control subjects were analyzed. Genotype analysis was performed through polymerase chain reaction (PCR) and then DNA direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional Logistic regression model.

RESULTSThe frequency of R264C single nucleotide polymorphism CC, CT and TT genotype in case group and controls was 84(77.8%), 22(20.4%), 2(1.8%) and 87(77.7%), 24(21.4%), 1(0.9%), respectively. CT genotype (OR=1.16, 95%CI: 0.53-2.55) and TT genotype (OR=1.44, 95%CI: 0.12-17.15) did not confer a significantly increased risk for breast cancer. No significant association was found between T allele and susceptibility for breast cancer under analysis according to menopausal status and body mass index.

CONCLUSIONR264C polymorphism in CYP19A1 gene is not a candidate locus for low penetrance breast cancer susceptibility in Shanghai group of Chinese population and not recommended in clinical genetic test. Homozygous T allele of R264C is not common in Shanghai group of Chinese population.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; BRCA2 Protein ; genetics ; Base Sequence ; Breast Neoplasms ; genetics ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; Molecular Sequence Data ; Mutation ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Steroid 17-alpha-Hydroxylase ; genetics ; Young Adult

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