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Temporal muscle thickness measured on 3D MRI has recently been linked to prognosis in glioblastoma patients and may serve as an independent prognostic indicator. This single-center study looked at temporal muscle thickness and prognosis in patients with primary glioblastoma. Overall survival was the major study outcome. For a retrospective analysis from 2010 to 2020, clinical data from 102 patients with glioblastoma at the Department of Oncology Radiotherapy of the First Affiliated Hospital of Dalian Medical University were gathered. Fifty-five cases from 2016 to 2020 contained glioblastoma molecular typing data, of which 45 were IDH wild-type glioblastomas and were analysed separately. TMT was measured on enhanced T1-weighted magnetic resonance images in patients with newly diagnosed glioblastoma.Overall patient survival (OS) was calculated by the Kaplan–Meier method and survival curves were plotted using the log-rank-sum test to determine differences between groups, and multifactorial analyses were performed using a Cox proportional-risk model.The median TMT for 102 patients was 6.775 mm (range: 4.95–10.45 mm). Patients were grouped according to median TMT, and the median overall survival (23.0 months) was significantly longer in the TMT > median group than in the TMT median group (P 0.001; Log-rank test). Analysing 45 patients with IDH wild type alone, the median overall survival (12 months) of patients in the TMT > median group was significantly longer than that of patients in the TMT ≤ median group (8 months) (P < 0.001; Log-rank test).TMT can serve as an independent prognostic factor for glioblastoma. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea. Thus, TKIs with high selectivity are being developed. TH-4000, a prodrug that generated an active form TH-4000Effector (TH-4000E) under hypoxic condition, was evaluated in this research. We found that TH-4000E ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium) (1–1000 nM) had potent and highly selective toxic effects on HER2+ breast cancer cells and inhibited the phosphorylation of HER family kinases at lower doses than that of Lapatinib and Tucatinib. TH-4000E activated Caspase-3 and induced apoptosis through a reactive oxygen species (ROS)-dependent pathway. The prodrug TH-4000 ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide) (50 mg/kg) effectively suppressed the tumor growth with less liver damage in mouse tumor models. This hypoxia-targeted strategy has possessed advantage in avoiding drug-induced liver damage, TH-4000 could be a promising drug candidate for the treatment of HER2+ breast cancer. [ABSTRACT FROM AUTHOR]

Increasing evidence has demonstrated that enhanced PHF20 expression plays a crucial role in cancer development and progression. However, little is known about the prognostic value of PHF20 expression in breast cancer (BRCA). In this study, we attempted to explore the expression pattern of PHF20 and its associations with prognosis and immune status in BRCA. The gene expression data and clinical information of 1109 BRCA samples were downloaded from TCGA database. The expression level of PHF20 protein was determined using UALCAN and HPA database. Kaplan–Meier method and CIBERSORT algorithm were used to analyze the associations of PHF20 expression with overall survival (OS) and immune microenvironment, respectively. Besides, GSEA analysis was conducted to explore potential biological functions and molecular mechanisms of PHF20 in BRCA. Moreover, starBase database was applied to construct a ceRNA nework. PHF20 was highly expressed in BRCA samples both at the transcriptional and protein level, and was strongly correlated with the OS and immune status. Univariable and multivariate Cox regression analyses identified PHF20 as an independent prognostic factor. Additionally, GSEA analysis showed that high PHF20 expression was closely associated with TGF-β signaling pathway, Wnt signaling pathway, and adherens junction. Furthermore, three ceRNA networks (AC037198.1/hsa-miR-223-3p/PHF20, CBR3-AS1/hsa-miR-223-3p/PHF20, and ZNF561-AS1/hsa-miR-223-3p/PHF20) were identified by starBase analysis. Functional experiments validated that PHF20 knockdown inhibited the cell viability and progression in BRCA cells. PHF20 overexpression was significantly associated with poor prognosis and immune status in BRCA, and could act as a potential novel prognostic biomarker for BRCA. [ABSTRACT FROM AUTHOR]

Programmed death receptor-1 (PD-1) blockade have achieved some efficacy but only in a fraction of patients with hepatocellular carcinoma (HCC). Programmed cell death 1 ligand 1 (PD-L1) binds to its receptor PD1 on T cells to dampen antigen-tumor immune responses. However, the mechanisms underlying PD-L1 regulation are not fully elucidated. Herein, we identify that tumoral Prdm1 overexpression inhibits cell growth in immune-deficient mouse models. Further, tumoral Prdm1 overexpression upregulates PD-L1 levels, dampening anti-tumor immunity in vivo, and neutralizes the anti-tumor efficacy of Prdm1 overexpression in immune-competent mouse models. Mechanistically, PRDM1 enhances USP22 transcription, thus reducing SPI1 protein degradation through deubiquitination, which enhances PD-L1 transcription. Functionally, PD-1 mAb treatment reinforces the efficacy of Prdm1-overexpressing HCC immune-competent mouse models. Collectively, we demonstrate that the PRDM1-USP22-SPI1 axis regulates PD-L1 levels, resulting in infiltrated CD8+ T cell exhaustion. Furthermore, PRDM1 overexpression combined with PD-(L)1 mAb treatment provides a therapeutic strategy for HCC treatment. Members of the PRDI-BF1 and RIZ homology domain (PRDM) family have been involved in the regulation of several pathological conditions, including cancer. Here the authors show that PRDM1/BLIMP1 promotes immune evasion by regulating PD-L1 expression in hepatocellular carcinoma cells. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloproteinase (ADAM) family members are known to process the target membrane-bound molecules through the quick induction of their protease activities under interaction with other molecules, which have diverse roles in tissue morphogenesis and pathophysiological remodeling. Among these, ADAM17 is a membrane-bound protease that sheds the extracellular domain of various receptors or its ligands from the cell membrane and subsequently activates downstream signaling transduction pathways. Importantly, breast cancer remains a mainspring of cancer-induced death in women, and numerous regulatory pathways have been implicated in the formation of breast cancer. Substantial evidence has demonstrated that an obvious increased in ADAM17 cell surface expression has been discovered in breast cancer and was shown to be associated with mammary tumorigenesis, invasiveness, and drug resistance. Over the last decades, it has received more than its share of attention that ADAM17 plays a potential role in breast cancer, including cell proliferation, invasion, angiogenesis, apoptosis, and trastuzumab resistance. In our review, we discuss the mechanisms through which ADAM17 acts on breast cancer tumorigenesis and progression. Thus, this will provide further impetus for exploiting ADAM17 as a new target for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Previous studies have examined the effect of aspirin intake on the mortality in breast cancer, but the results are inconsistent. A meta-analysis was performed to assess the association with all available studies. Relevant studies were identified by searching PubMed and EMBASE to November 2014. We calculated the summary relative risks (RRs) and 95 % confidence intervals (CIs) using random-effects models. For this meta-analysis, eight cohort studies and two nested case-control studies were included. The analysis included 26,931 participants for postdiagnosis aspirin use and 673,453 participants for prediagnosis aspirin use, followed up over a period of between 2.6 and 30 years. The results showed that patients who used aspirin after diagnosis had a RR of 0.73 (95 % CI = 0.54-0.98, P = 0.04) for breast cancer-specific mortality compared to those who did not use aspirin. Those who used aspirin after diagnosis (vs. non-users) had a RR of 0.84 (95 % CI = 0.63-1.12, P = 0.24) for all-cause mortality. Prediagnostic exposure to aspirin was associated with neither breast cancer-specific mortality (RR = 1.04, 95 % CI = 0.75-1.45, P = 0.80) nor all-cause mortality (RR = 1.04, 95 % CI = 0.61-1.78, P = 0.89). Significant heterogeneity among included studies may be due to a single study, after removing which the significant association between postdiagnosis aspirin use and breast cancer-specific mortality disappeared; however, prediagnosis aspirin use achieved a borderline significant association with risk of all-cause mortality (RR = 0.81, 95 % CI = 0.68-0.97, P = 0.03). In conclusion, aspirin use might has, if any, only a small effect on the survival of breast cancer patients based on current evidence. [ABSTRACT FROM AUTHOR]

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To derive a more precise estimation, we carried out not only an updated meta-analysis but also a combined analysis based on all the available studies estimating the association between MTHFR C677T and/or A1298C and breast cancer risk. With respect to C677T polymorphism, the results suggested that 677T allele was associated with significantly elevated breast cancer risk in overall analysis (T vs. C: OR 1.073, 95 % CI 1.028-1.120; TT vs. CC: OR 1.177, 95 % CI 1.072-1.293; TT vs. CC + CT: OR 1.175, 95 % CI 1.073-1.288); Stratifying by ethnicity, significantly increased risk was only found in East Asians (T vs. C: OR 1.150, 95 % CI 1.039-1.273; TT vs. CC: OR 1.441, 95 % CI 1.145-1.814; TT vs. CC + CT: OR 1.413, 95 % CI 1.148-1.739); When stratified by menopausal status, statistically significant association was found for postmenopausal women (CT + TT vs. CC: OR 1.092, 95 % CI 1.011-1.179). In regard to A1298C polymorphism, no significant associations were found between the polymorphism and breast cancer risk. With respect to MTHFR haplotypes, significantly elevated breast cancer risk was associated with 677T-1298C for overall result (OR 1.498, 95 % CI 1.143-1.962) and for Caucasians (OR 2.088, 95 % CI 1.277-3.416) when compared with 677C-1298A; Haplotype 677C-1298C might provide higher protection than 677C-1298A in East Asians (OR 0.840, 95 % CI 0.742-0.949). The combined genotypes for C677T and A1298C produced a significant OR for the 677TT/1298AC relative to 677CC/1298AA in overall population (OR 2.047, 95 % CI 1.275-3.288); When stratified by ethnicity, significant ORs were only found for East Asians (677CC/1298CC vs. 677CC/1298AA: OR 0.686, 95 % CI 0.478-0.985; 677TT/1298AC vs. 677CC/1298AA: OR 2.181, 95 % CI 1.179-4.035). The findings suggest that the MTHFR C677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer. [ABSTRACT FROM AUTHOR]

Previous studies concerning the association between physical activity (PA) and mortality in breast cancer yielded mixed results. We investigated the association by performing a meta-analysis of all available studies. Relevant studies were identified by searching PubMed and EMBASE to January 2014. We calculated the summary relative risk (RR) and 95 % confidence intervals (CIs) using random-effects models. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Sixteen cohort studies involving 42,602 patients of breast cancer were selected for meta-analysis. The analyses showed that patients who participated in any amount of PA before diagnosis had a RR of 0.82 (95 % CI 0.74-0.91) for breast cancer-specific mortality (vs. low PA). Those who participated in high PA and moderate PA before diagnosis had a RR of breast cancer-specific mortality of 0.81 (95 % CI 0.72-0.90) and 0.83 (95 % CI 0.73-0.94), respectively. Similar inverse associations of prediagnosis PA were found for all-cause mortality. Postdiagnosis PA on breast cancer-specific and all-cause mortality also showed the same results. Stratifying by body mass index (<25 vs. ≥25) or menopausal status, all the subgroups experienced benefits with PA, with a stronger mortality reduction among overweight women than normal weight women and among postmenopausal women than premenopausal women. A linear and significant dose-response association was only found for breast cancer-specific or all-cause mortality and prediagnosis PA ( P for nonlinearity = 0.07 and 0.10, respectively). In conclusion, both prediagnosis and postdiagnosis PA were associated with reduced breast cancer-specific mortality and all-cause mortality. [ABSTRACT FROM AUTHOR]

Breast cancer during lactation is very rare, accounting for <3 % of all breast cancers. Its diagnosis and treatment is often delayed during pregnancy. We report a case of female lactating breast carcinoma in a 29-year old patient. The disease was stage IIIB (T4N1M0). The patient received preoperative induction chemotherapy and high-dose chemotherapy with peripheral blood stem cell support, followed by adjuvant chemotherapy and endocrine therapy. The metastases were detected 17 months after operation, palliative treatment including different chemotherapy for 60 cycles, locoregional radiotherapy and endocrine therapy. The total number of cycles of chemotherapy was 67, and the survival time was 118 months. We discuss the diagnosis and treatment options for breast cancer during lactation, based on a literature review. [ABSTRACT FROM AUTHOR]

Background: Regorafenib is a novel multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). Hypertension is one of the major adverse events of this agent, but to date the incidence and risk of hypertension with regorafenib have not been systematically investigated. We have conducted a systematic review and meta-analysis of published clinical trials to determine its overall incidence and risk. Methods: PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies published up to September 9, 2013. Eligible studies were prospective phase II or III clinical trials using regorafenib in cancer patients with data on hypertension available. The incidence and relative risk (RR) of hypertension were calculated using a random-effects model. Results: Data from a total of 1,069 patients (regorafenib n = 750; controls n = 319) from five clinical trials were included for analysis. The overall incidence of all-grade and high-grade hypertension were 44.4 % [95 % confidence interval (CI) 30.8-59.0 %) and 12.5 % (95 % CI 5.2-27.1 %), respectively. The use of regorafenib in cancer patients was associated with a significantly increased risk of all-grade (RR 3.76, 95 % CI 2.35-5.99) and high-grade (RR, 8.39, 95 % CI 3.10-22.71) hypertension. The risk might vary with tumor types ( P = 0.000). Conclusions: Patients with cancer receiving regorafenib have a significantly higher risk of developing hypertension. Close monitoring and appropriate management of this hypertension are strongly recommended. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the efficacy and safety of docetaxel plus cyclophosphamide (TC) compared with docetaxel, anthracycline, and cyclophosphamide (TEC) in neoadjuvant treatment of triple negative or HER2 positive breast cancer. Eligible breast cancer patients were randomized to receive six cycles of TC or TEC. The primary end point was pathological complete remission (pCR). Secondary end points included safety, clinical response rate, and survival outcome. One hundred and two patients were initially randomized and 96 patients were available for efficacy analysis. 96.9 % patients were treated with epirubicin as an anthracycline agent. pCR rates were 6.8 % (3/45) and 17.6 % (9/51) in TC and TEC group, respectively, P = 0.113. After a mean follow up of 20 (3–36) months, non-anthracycline-containing TC regimen treatment resulted in a worse event-free survival (adjusted hazard ratio [HR] 2.42; 95 % CI 1.11–5.30) and disease-free survival (HR 2.85; 95 % CI 1.21–6.74) compared with TEC regimen, which was more apparent in triple negative subtype. Severe adverse event rates were similar, except that patients treated with TEC had a higher rate of neutropenia and leucopenia. TEC treatment had a superior survival outcome and trend of higher pCR rate compared with TC in this trial setting, especially in triple negative subtype, which deserves further validation. [ABSTRACT FROM AUTHOR]

MiR-424 plays an important role via promoting the monocytic differentiation in many human leukemia cell lines. Here, we report that miR-424 decreased miR-125b expression to 36 % by directly targeting caudal type homeobox 2. However, miR-424 also decreased expression of Fes, PU.1 and colony-stimulating factor receptor (MCSFR). As Fes, PU.1 and MCSFR were down-regulated by over-expression of miR-125b (unpublished work), a similar effect of miR-424 and Fes siRNA on CD64, Egr-1, Egr-2 and CEBPA indicates that Fes may be an important downstream target of miR-424. We hypothesize that miR-424 promotes monocytic differentiation by regulating other critical factors and miR-424 has high affinity for these factors. For the first time, the molecular mechanism of miR-424 during monocytic differentiation of U937 cells has been elucidated in this study. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the impact of the negative lymph node (LN) count on the survival of the breast cancer patients in early stage after the axillary dissection. Methods: The breast cancer patients with TNM stage between January 2001 and December 2005 in Jiangsu Cancer Hospital, who underwent the axillary LNs dissection, were enrolled in this study. We analyzed the data of these patients including information of follow-up and postoperative pathological results. All patients were divided into two groups according to the axillary LN status and each group was divided into four subgroups according to the negative LN count. Cox regression analysis was performed to screen the pathological factor including the negative LN count on the survival and to compare the different negative LN count on the survival. Results: COX proportional hazard regression model showed that the survival of the breast cancer was significantly associated with the negative LN count. In TN group, when the negative LN count was 3 or less, 4 to 5, 6 to 9 and 10 or more, the median survival time was (82.6 ± 4.1) months, (101.5 ± 1.3) months, (104.7 ± 1.0) months, and (110.5 ± 0.9) months respectively ( P < 0.05). In TN group, when the negative LN count was 6 or less, 7 to 8, 9 to 10 and 11 or more, the median survival time was (95.4 ± 1.9) months, (101.8 ± 1.1) months, (104.9 ± 1.0) months, and (106.5 ± 0.9) months respectively ( P< 0.05). Conclusion: The negative LN count can reflect the adequacy of the axillary dissection. Increasing negative LN count is independently associated with improved survival in pTNM or pTNM staging breast cancer patients. The negative LN count should be considered for incorporation into staging for breast cancer with the axillary LN dissection. [ABSTRACT FROM AUTHOR]

Ultraconserved elements (UCEs) are the most extreme representatives of conserved non-coding sequences. Recent studies have indicated that UCEs are not mutation cold regions and likely to be concerned with cancers, including breast cancer (BC). In this study, we first screened common single-nucleotide polymorphisms (SNPs) (minor allele frequency, MAF > 0.05) in Chinese population located in 481 UCEs sequences and selected seven SNPs (rs17049105, rs13020355, rs2682406, rs2056116, rs11190870, rs9572903, and rs8004379) of uc.51, uc.82, uc.133, uc.140, uc.302, uc.353, and uc.368, respectively. A two-stage case-control study of BC with a total of 1,497 cases and 1,497 controls in Chinese population was conducted to test the hypothesis that these SNPs of UCEs are associated with BC risk. Stage I with 735 cases and 735 controls was designed to discover the risk variants, followed by stage II with 762 cases and 762 controls to validate the significant variants. In stage I, although the genotype distributions of all seven SNPs were not significantly different between BC cases and controls, logistic regression analyses revealed that the variant genotypes of rs8004379 were significantly associated with the increased risk of BC (dominant model: adjusted OR = 1.27, 95% CI = 1.01-1.58, P = 0.039). We then selected two SNPs, rs8004379 A/C and rs2056116 A/G, with lowest P values of the associations into the stage II analysis. However, none of above two SNPs were significantly associated with BC risk in both stage II and pooled set (rs8004379 AC/CC vs. AA: adjusted OR = 0.88, 95% CI = 0.68-1.13 for stage II and adjusted OR = 1.09, 95% CI = 0.92-1.29 for the pooled set; rs2056116 AG/GG vs. AA: adjusted OR = 1.12, 95% CI = 0.87-1.45 for stage II and adjusted OR = 1.11, 95% CI = 0.94-1.31 for the pooled set). These findings did not support a significant association between UCEs SNPs and the risk of BC in Chinese population. [ABSTRACT FROM AUTHOR]

Disruption of the circadian rhythm has been reported to increase the risk of breast cancer. A single nucleotide polymorphism (SNP) rs2305160 in Neuronal PAS domain protein 2 ( NPAS2), the largest circadian gene, was identified as a breast cancer susceptibility locus. In the current study, we found a novel functional SNP (rs3739008) located at 3′UTR of NPAS2 and the C to T changing of the SNP may disrupt the binding of microRNA- (miR-) 17-5p and miR-519e to the 3′UTR of NPAS2. We then typed this SNP in case-control studies of both Chinese and Germany populations to test its putative associations with breast cancer risk. However, we failed to find any significant associations by different genetic models (dominant genetic model, adjusted OR = 1.13, 95% CI = 0.95-1.35 for the Chinese population and adjusted OR = 0.99, 95% CI = 0.85-1.16 for the Germany population). Although we did not find significant associations at population levels from both Chinese and Germany case-control studies, due to the functional relevance of rs3739008 on NASP2 expression, it will be promising to investigate the influence of this variant on clinical characteristics of breast cancer and breast cancer survival. [ABSTRACT FROM AUTHOR]

Trinucleotide repeat-containing 9 (TNRC9), a high mobility group chromatin-associated protein, has been implicated in breast cancer metastasis to the bone. Recently, several single nucleotide polymorphisms (SNPs) of TNRC9 were identified as novel breast cancer susceptibility loci by whole genome association studies, especially in estrogen receptor (ER) positive tumors. In the present case-control study of 1,049 breast cancer patients and 1,073 cancer-free controls in a Chinese population, we genotyped three polymorphisms (rs3803662C/T, rs12443621A/G, and rs8051542C/T) of the TNRC9 gene using the SNPstream 12-plex platform to test the hypothesis that these SNPs are associated with breast cancer risk in this population. None of the three polymorphisms was significantly associated with breast cancer risk in the whole data set ( P = 0.151, 0.644, and 0.737 for rs3803662, rs12443621. and rs8051542, respectively). However, rs12443621 AG/GG genotypes were significantly associated with increased risk of ER positive breast cancer (OR = 1.38, 95% CI = 1.01-1.88), compared with homozygote AA. In addition, a borderline significantly increased risk was also observed for the variant genotypes (CT/TT) of rs8051542 C/T compared with the wild-type genotype (CC) (adjusted OR = 1.26, 95% CI = 0.99-1.60). Interestingly, a significant interaction was detected between rs12443621A/G and ER status on breast cancer risk in a case-only analysis ( P for interaction = 0.004). These findings suggest that genetic variants of TNRC9 may contribute to the development of ER positive breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent cancer worldwide. Many published articles have evaluated the association between the transforming growth factor beta 1 (TGFB1) T29C polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 12 studies including 10,417 breast cancer cases and 11,455 controls were identified. Overall, no significant associations between the TGFB1 T29C polymorphism and breast cancer risk were found for CC versus TT (OR = 1.00, 95% CI = 0.92-1.09), TC versus TT (OR = 0.98, 95% CI = 0.93-1.05), CC/TC versus TT (OR = 0.99, 95% CI = 0.93-1.05), and CC versus TC/TT (OR = 1.00, 95% CI = 0.93-1.08). In the subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in all genetic models. In conclusion, the present meta-analysis suggests that the TGFB1 T29C polymorphism is not a low-penetrant risk factor for developing breast cancer. [ABSTRACT FROM AUTHOR]

RecQ helicases play a central role in maintaining genome stability and may interact with some important cancer-related proteins such as BRCA1. Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature aging and cancer predisposition, including breast cancer. In this case–control study of 1,004 breast cancer cases and 1,008 controls, we tested the hypothesis that non-conservative amino acid exchanges in WRN (leu1074Phe), BLM (Met298Thr) and BRCA1 (Pro871Leu) are independently or jointly associated with the risk of breast cancer in Chinese women. We found that the variant genotype of WRN Leu1074Phe was associated with a 1.36-fold significantly increased risk of breast cancer (OR = 1.36, 95% CI = 1.06–1.74). Moreover, a significant gene–environment interaction was evident between WRN leu1074Phe and age at menarche ( Pint = 0.02). Subjects carrying Phe/Phe genotype and with earlier age at menarche had 3.58-fold increased risk of breast cancer (OR = 3.58, 95% CI = 2.54–5.05). However, we did not find the significant main effect of polymorphisms in BLM and BRCA1 and also no locus–locus interactions were identified between WRN, BLM and BRCA1. These findings indicate that WRN leu1074Phe variant may contribute to the susceptibility of breast cancer in Chinese women. [ABSTRACT FROM AUTHOR]