Correlation of miR-155 on formalin-fixed paraffin embedded tissues with invasiveness and prognosis of breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the potential use of miR-155 as novel breast cancer biomarker.</p><p><b>METHODS</b>There were 88 breast cancer patients underwent modified mastectomy and had detailed clinical follow-up information. Extracting RNA from the formalin-fixed paraffin embedded (FFPE) samples, miR-155 levels were quantified by real-time-PCR. miR-155 levels among clinico-pathological variables were accessed by Mann Whitney-U test. Overall survival curve was derived from Kaplan-Meier estimates and the curve was compared by Log-rank test. Cox regression analysis was used for multivariate analysis. All statistical tests were two-sided.</p><p><b>RESULTS</b>Significantly higher miR-155 level was found in tumor tissue compared to paired normal tissue (t = 6.75, P = 0.000). A potential relationship between miR-155 levels and existing clinico-pathological parameters of breast cancer, such as menstrual status, tumor size, nodal involvement, stage of disease, hormone receptor status, HER-2 status, histological grade or tumor subtype was investigated. Up-regulated miR-155 level was observed in breast cancer with lymph node metastasis, pT3+4, advanced TNM stage, HER-2 positive and with vascular invasion (Z = -6.320 to -2.041, P = 0.000 to 0.041). When considering 2(-ΔCt) = 4.87 (median level) as cut-off value, patients with miR-155 up-regulation showed a positive association towards a shorter overall survival (χ(2) = 6.396, P = 0.011). In Cox multivariate analysis, miR-155 expression on FFPE was shown an inverse trend for outcomes of breast cancer (HR = 1.58, 95%CI: 0.87 - 3.16, P = 0.082).</p><p><b>CONCLUSIONS</b>miR-155, as an oncomir, promotes lymph node involvement and vascular invasion and accompanies over-expressed HER-2 on breast cancer FFPE tissue. It suggests that miR-155 could predict the invasiveness.</p>

Correlation of miR-195 with invasiveness and prognosis of breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the potential role of miR-195 on invasiveness and prognosis of breast cancer.</p><p><b>METHODS</b>The RNA in formalin-fixed paraffin embedded (FFPE) of 88 breast cancer patients with primary tumors was extracted, and miR-195 levels were quantified by quantitative real-time polymerase chain reaction (real-time PCR). The relationship of miR-195 levels and clinicopathological variables were assessed by Mann Whitney-U test. Recurrence-free survival and overall survival curves were derived from Kaplan-Meier estimates and the curves were compared by Log-rank tests. Cox regression analysis was used for multivariate analysis. All statistical tests were two-sided.</p><p><b>RESULTS</b>The levels of miR-195 in the breast cancer with histological high grade, tumor size of T3-4, lymph nodal involvement or vessel invasion were significantly down-regulated, compared with those of patients with histological low grade (Z = -2.271, P = 0.023), tumor size of T1-2 (Z = -2.687, P = 0.007), no lymph node metastasis (Z = -1.967, P = 0.049) and vessel invasion (Z = -2.432, P = 0.015). In addition, no statistically significant difference (P > 0.05) was identified between miR-195 levels and hormone receptors status, HER-2 expression, TNM stage, tumor types, recurrence and menstrual status. When considering 2(-ΔCt) = 0.270 (median level) as cut-off value, Kaplan-Meier survival analysis indicated that patients with high miR-195 level showed a positive association towards a longer survival, either recurrence-free survival (χ(2) = 5.985, P = 0.014) or overall survival (χ(2) = 30.05, P = 0.000). In a multivariate analysis, miR-195 expression on FFPE correlated significantly with outcomes of breast cancer (HR = 0.040, 95%CI: 0.009 - 0.179, P = 0.000) and was independent of other prognostic factors.</p><p><b>CONCLUSIONS</b>It suggests that miR-195 expression on FFPE is inversely correlated with histological high grade, bigger tumor size, lymph node involvement, vessel invasion. Furthermore, as independent prognostic factor, low miR-195 significantly contributes to poor outcomes of breast cancer.</p>

Correlation of polymorphism rs1563828 in MDM4 gene with breast cancer risk and onset age / 中华外科杂志

<p><b>OBJECTIVE</b>To explore effect of polymorphism rs1563828 (C > T) in human murine double minute 4 gene (MDM4) on genetic susceptibility for early-onset breast cancer and potential association with age of onset of breast cancer.</p><p><b>METHODS</b>One hundred and twenty-four early-onset breast cancer patients (age ≤ 35 years at time of diagnosis) from independent families admitted from January 2006 to June 2010 and 101 age-matched healthy control subjects were analyzed. Genotype analysis was conducted by polymerase chain reaction and then MALDI-TOF-MS assay. Association of genotype distribution and breast cancer risk was evaluated by χ(2) test. The odd-ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional Logistic regression model. The t test was used to compare the age and demographic differences among groups.</p><p><b>RESULTS</b>The frequency of rs1563828 polymorphism genotypes in control group were CC 43.6% (44/101), CT 42.6% (43/101), TT 13.9% (14/101), and in case group were 42.7% (53/124), 46.0% (57/124), 11.3% (14/124), respectively. No significant difference (χ(2) = 0.449, P = 0.799) was reached by χ(2) test. rs1563828CT or TT genotype does not confer a significantly increased risk for breast cancer compared with CC genotype after adjusting for age, menarche in Logistic regression analysis (OR = 1.024, 95%CI: 0.581 - 1.806, P = 0.934). TT carriers were observed to develop breast cancer earlier than CC/CT carriers [(30 ± 4) years vs. (32 ± 3) years, P = 0.028].</p><p><b>CONCLUSIONS</b>The rs1563828(C > T) polymorphism in MDM4 gene may not confer risk to breast cancer, especially for early-onset breast cancer patients. Homozygous TT of rs1563828 is associated with younger age to develop breast cancer.</p>

5589del8: the recurrent mutation of BRCA1 gene in Chinese breast cancer patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Three 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.</p><p><b>CONCLUSION</b>BRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.</p>

CHEK2 c.1100delC may not contribute to genetic background of hereditary breast cancer from Shanghai of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of CHEK2 c.1100delC mutation among non-BRCA1/BRCA2 familial/early-onset breast cancer patients in Shanghai.</p><p><b>METHODS</b>One 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.</p><p><b>RESULTS</b>No 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.</p><p><b>CONCLUSION</b>CHEK2 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.</p>

Prevalence of Val158Met polymorphism in COMT gene on non-BRCA1/2 hereditary breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the prevalence of Val158Met polymorphism in Catechol-O-methyltransferase (COMT) gene and its effect on genetic susceptibility for breast cancer in Shanghai population.</p><p><b>METHODS</b>A total of 114 patients with BRCA1/BRCA 2 negative hereditary breast cancer from independent families and 121 age-matched healthy controls were analyzed. Genotype analysis was conducted by 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.</p><p><b>RESULTS</b>The frequency of Val158Met polymorphism GG, GA and AA genotype in case group and control was 0.58 (65), 0.32 (36), 0.10 (11) and 0.60 (66), 0.35 (41), 0.03 (3), respectively. The frequency of allele-containing genotypes is significantly higher in early-onset breast cancer patients (0.57) than in familial ones (0.35). Compared with GG (Val/Val) genotype, AA (Met/Met) genotype confers a significantly increased risk for breast cancer (adjusted OR = 3.15; 95% CI, 0.70 - 14.19), especially among premenopausal women (adjusted OR = 9.98; 95% CI, 1.00 - 99.64). Borderline significantly association was found between AA genotype (adjusted OR = 7.57; 95% CI, 0.57 - 101.28) and susceptibility for breast cancer in BMI < or = 23 kg/m(2) group.</p><p><b>CONCLUSIONS</b>Val158Met polymorphism in COMT gene could be a candidate for low penetrance breast cancer susceptibility in Shanghai population, especially among premenopausal women and early-onset breast cancer patients.</p>

BRCA1 and BRCA2 gene mutations of familial breast cancer from Shanghai in China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of BRCA1 and BRCA2 gene mutations among breast cancer patients with affected relatives in Shanghai of China.</p><p><b>METHODS</b>Thirty-five breast cancer patients who had at least one first-degree relative affected were analyzed, among whom 13 patients suffered from breast cancer at age of less than 40 years. A comprehensive BRCA1 and BRCA2 mutation analysis was performed through denaturing high-performance liquid chromatography (DHPLC) and subsequent DNA direct sequencing.</p><p><b>RESULTS</b>Four mutations in BRCA1 gene, including 2 novel splice-site mutations (IVS17-1G>T, IVS21+1G>C) and 2 frameshift mutations (1100delAT; 5640delA) were identified. One frameshift mutation (5802delAATT) was detected in exon 11 of BRCA2. Additional 12 novel single nucleotide polymorphisms(SNPs) were detected, including a novel unclassified variant and 7 novel intronic variants in BRCA1, and 4 novel intronic variants in BRCA2, with which all caused no alteration of amino acid coding. The mutation frequency of BRCA1 and BRCA2 in patients with family history was 11.4% and 2.9%, respectively.</p><p><b>CONCLUSION</b>Two novel mutations in BRCA1 may be mutations characterized to familial breast cancer of Chinese Shanghai population. The BRCA2 may contribute to mutation less than BRCA1 in familial breast cancer. Our data contribute to information on mutation spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing policy in China.</p>

Effect of R264C polymorphism in CYP19A1 gene on BRCA1/2-negative hereditary breast cancer from Shanghai population of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Aromatase, 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.</p><p><b>METHODS</b>One 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>R264C 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.</p>

Association of -160(C-->A) polymorphism in CDH1 gene with gastric cancer risk in Fujian Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>CDH1, encoding E-cadherin, is an important tumor suppressor gene. The present study aims to investigate the association of -160(C-->A) polymorphism in CDH1 gene with susceptibility to gastric cancer in Fujian province.</p><p><b>METHODS</b>One hundred and two patients from independent families and 101 healthy control subjects were analyzed. Genotype analysis was performed through polymerase chain reaction-based denaturing high performance liquid chromatography. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression model.</p><p><b>RESULTS</b>The frequencies of -160(C-->A) polymorphism CC, CA and AA genotype in case group and controls were 58(56.9%), 38(37.3%)ì6(5.9%) and 55(54.5%), 41(40.6%), 5(5%), respectively. AA genotype did not present a significantly increased risk for gastric cancer (OR=1.12; 95% CI:0.32-3.95). No association was found between A allele and clinicopathological characteristics of gastric cancer.</p><p><b>CONCLUSION</b>-160(C-->A) polymorphism in CDH1 gene promoter region may not be in association with genetic susceptibility to gastric cancer in Chinese population from Fujian.</p>