Clinicopathological Features of Breast Cancer in Relation to Exposure of Cycling Reproductive Hormones: A Multicenter Retrospective Study of 14,731 Patients Diagnosed with Invasive Breast Cancer.

BACKGROUND Reproductive period for women, begins at menarche and ends at menopause, which represented the total time period of exposure to cycling reproductive hormones. The potential associations between clinicopathological features and the exposure of cycling reproductive hormones has not been extensively studied. The retrospective study enrolled 14,731 patients diagnosed with invasive breast cancer was designed to evaluate factors associated with the reproductive period on breast cancer type and patient outcomes. MATERIAL AND METHODS 14, 731 female breast cancer (BC) patients from Western China Clinical Cooperation Group (WCCCG) between January 1, 2008 to December 31, 2017 were identified. Unconditional logistic regression was performed to assess the associations between clinicopathological features and menarche age, menopause age, and reproductive years. The differences in risk factors between lower and higher number of reproductive years (<35 and ³35 yrs) were examined with the chi-square test. RESULTS First, patients with late menarche age were more likely to present with tumors of higher histological grade and larger sizes. Second, the findings suggested a higher likelihood of smaller tumor sizes in postmenopausal patients with a greater length of reproductive years. Conversely, higher histological grade was associated with this group of patients, compared to their counterparts with shorter reproductive years. Third, in luminal breast cancer, patients with a greater length of reproductive years were more probably present larger tumor. CONCLUSIONS Our findings indicated that several clinicopathologic factors including tumor size and histological grade were associated with the length of reproductive years in patients diagnosed with breast cancer.

Advances in Imaging in Evaluating the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer.

Neoadjuvant chemotherapy (NAC) is increasingly widely used in breast cancer treatment, and accurate evaluation of its response provides essential information for treatment and prognosis. Thus, the imaging tools used to quantify the disease response are critical in evaluating and managing patients treated with NAC. We discussed the recent progress, advantages, and disadvantages of common imaging methods in assessing the efficacy of NAC for breast cancer.

The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is associated with breast cancer subtype susceptibility in southwestern China.

Methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme, is reportedly involved in several cancer types. The MTHFR C677T polymorphism influences many biological processes, including tumorigenesis. However, the association between the MTHFR C677T polymorphism and breast cancer (BC) subtypes is not fully understood. In this study, the MTHFR C677T polymorphism was genotyped in 490 individuals with or without BC from southwestern China. Analysis of the association between the MTHFR C677T polymorphism and BC revealed that there was a significant association between the MTHFR C677T polymorphism and triple-negative breast cancer (TNBC) (OR = 2.83, 95% CI: 1.12-9.51, P = 0.0401). Furthermore, the MTHFR C677T polymorphism can also serve as a protective factor in luminal A breast cancer (OR = 0.57, 95% CI: 0.34-0.94, P = 0.0258). Evaluation of the association between the MTHFR C677T polymorphism and clinical characteristics indicated that people who suffered from hypertension had an increased risk for BC (OR = 2.27; 95% CI: 1.08-4.6; P = 0.0264), especially TNBC (OR = 215.38; 95% CI: 2.45-84430.3; P = 0.0317). Our results suggest that the MTHFR C677T polymorphism is significantly associated with susceptibility to luminal B breast cancer and TNBC.

Overexpression of serum exosomal HOTAIR is correlated with poor survival and poor response to chemotherapy in breast cancer patients.

To investigate the source of serum exosomal HOTAIR, to uncover the diagnostic and prognostic values of serum exosomal HOTAIR, and to discern the expression of serum exosomal HOTAIR between neoadjuvant chemotherapy and response to tamoxifen therapy. Samples were collected from the Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan. Exosomes were isolated from serum, cell culture medium and tumor tissues. We used transmission electron microscopy and western immunoblotting assay to characterize exosomes, and real-time PCR (qPCR) to assess HOTAIR expression. Neoadjuvant chemotherapy and tamoxifen therapy were carried out according to established guidelines. Breast cancer patients expressed higher serum exosomal HOTAIR than did healthy individuals (P\0.001). Serum exosomal HOTAIR levels 3 months after surgery were markedly decreased compared with levels before surgery (P\0.001), and the expression level of exosomal HOTAIR in cell culture medium increased with time in both breast cancer cell lines (72 h greater than 48 h greater than 24 h, 48 h vs 24 h [ [P less than 0.05]; 72 h vs 24 h [P less than 0.01]. Expression of serum exosomal HOTAIR in nude mice was notably greater than in the mock control group (P less than 0.001). The results of the ROC analysis revealed an AUC for serum exosomal HOTAIR of 0.9178 with a 95% CI of 0.8407-1.017 (P less than 0.01). The AUC for the CA15-3 cell line was 0.7378 (95% CI, 0.5585-0.9170; P = 0.03). High expression of exosomal HOTAIR led to a worse disease-free survival (P = 0.0481) and overall survival (P = 0.0463). In the high-expression chemotherapy group, six patients achieved a partial response (PR) and eight demonstrated stable disease (SD) and nine patients achieved PR and two SD in the low-expression group (P = 0.048). In the low-expression tamoxifen group, one patient had a recurrence of breast cancer and another 10 patients exhibited no recurrence, while six showed recurrence, and seven had none in the highexpression group (P = 0.035). We isolated exosomes successfully, and demonstrated that serum exosomal HOTAIR originated from primary breast cancer tissue. We conclude that serum exosomal HOTAIR exhibits the potential to be a diagnostic and prognostic biomarker. High expression of serum exosomal HOTAIR was also correlated with poor neoadjuvant chemotherapy and response to tamoxifen therapy.

Clinicopathologic Factors Related to the Histological Tumor Grade of Breast Cancer in Western China: An Epidemiological Multicenter Study of 8619 Female Patients.

BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2 cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti-HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.

Mithramycin A suppresses basal triple-negative breast cancer cell survival partially via down-regulating Krüppel-like factor 5 transcription by Sp1.

As the most malignant breast cancer subtype, triple-negative breast cancer (TNBC) does not have effective targeted therapies clinically to date. As a selective Sp1 inhibitor, Mithramycin A (MIT) has been reported to have anti-tumor activities in multiple cancers. However, the efficacy and the mechanism of MIT in breast cancer, especially TNBC, have not been studied. In this study, we demonstrated that MIT suppressed breast cancer cell survival in a dosage-dependent manner. Interestingly, TNBC cells were more sensitive to MIT than non-TNBC cells. MIT inhibited TNBC cell proliferation and promoted apoptosis in vitro in time- and dosage-dependent manners. MIT suppressed TNBC cell survival, at least partially, by transcriptionally down-regulating KLF5, an oncogenic transcription factor specifically expressed in basal TNBC. Finally, MIT suppressed TNBC cell growth in a xenograft mouse model. Taken together, our findings suggested that MIT inhibits basal TNBC via the Sp1/KLF5 axis and that MIT may be used for TNBC treatment.

Circular RNA hsa_circ_0001982 Promotes Breast Cancer Cell Carcinogenesis Through Decreasing miR-143.

Circular RNAs (circRNAs) are a type of noncoding RNAs generated from back-splicing, which have been verified to mediate multiple tumorigenesis. With the development of high-throughput sequencing, massive circRNAs are discovered in tumorous tissue. However, the potential physiological effect of circRNAs in breast cancer is still unknown. The purpose of this study is to investigate the expression profile of circRNA in breast cancer tissue and explore the in-depth regulatory mechanism in breast cancer tumorigenesis. In the present study, we screened the circRNA expression profiles in breast cancer tissue using circRNA microarray analysis. Totally 1705 circRNAs were identified to be significantly aberrant. Among these dysregulated circRNAs, hsa_circ_0001982 was markedly overexpressed in breast cancer tissue and cell lines. Bioinformatics analysis predicted that miR-143 acted as target of hsa_circ_0001982, which was confirmed by Dual-luciferase reporter assay. Loss-of-function and rescue experiments revealed that hsa_circ_0001982 knockdown suppressed breast cancer cell proliferation and invasion and induced apoptosis by targeting miR-143. In summary, our study preliminarily investigates the circRNA expression in breast cancer tissue and explores the role of competing endogenous RNA (ceRNA) mechanism in the progression, providing a novel insight for breast cancer tumorigenesis.

Relationship between mammographic calcifications and the clinicopathologic characteristics of breast cancer in Western China: a retrospective multi-center study of 7317 female patients.

BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.

TNF-α -308 A allele is associated with an increased risk of distant metastasis in rectal cancer patients from Southwestern China.

Tumor necrosis factor-α (TNF-α), an important factor in systematic inflammation, is reportedly involved in several cancer types. The TNF-α -308 G>A (rs1800629) polymorphism in the promoter region influences TNF-α production. The association between TNF-α -308 G>A polymorphism and colorectal cancer (CRC) is not fully understood, especially the connections between TNF-α -308 G>A polymorphism and clinical features of CRC. In this study, TNF-α -308 G>A polymorphism was genotyped in 1140 individuals with or without CRC from Southwestern China. In case-control studies, we found no association between TNF-α -308 G>A polymorphism and CRC risk. Analysis of the correlations between TNF-α -308 G>A polymorphism and clinical features of CRC revealed that TNF-α -308 A allele was associated with higher body mass index (BMI) larger tumor size, and distant tumor metastasis in all CRC patients. Notably, rectal cancer (a subtype of CRC) patients with TNF-α -308 A allele had a very high risk of distant tumor metastasis [odds ratio (OR) = 4.481; 95% confidence interval (CI): 2.072-9.693; P = 0.00025]. The association between TNF-α -308 A allele and distant tumor metastasis remained even significant after adjusting all clinical characteristics (OR = 7.099; 95% CI: 2.482-20.301; P = 0.000256) in rectal cancer patients. Our results suggested that TNF-α -308 A allele was significantly associated with distant tumor metastasis in rectal cancer patients.

A retrospective study of lymphatic transverse rectus abdominis myocutaneous/deep inferior epigastric perforator flaps for breast cancer treatment-induced upper-limb lymphoedema.

Breast cancer-related lymphoedema (BCRL) is a common and intractable complication. To evaluate the possible complications of using lymphatic transverse rectus abdominis myocutaneous/deep inferior epigastric perforator (TRAM/DIEP) flaps for breast reconstruction and BCRL treatment, 20 patients with moderate or severe BCRL were retrospectively enrolled between November 2012 and October 2014. 10 patients had undergone lymphatic TRAM/DIEP flap surgery were assigned to the surgery group. 10 patients unwilling to undergo reconstruction were assigned to the physiotherapy group treated with traditional physical therapy. Upper-limb movement and circumference were measured and patients' subjective assessment was assessed using a questionnaire. In the surgery group, all flaps were successfully transferred. BCRL in 8 patients was improved by one level. The upper-limb circumference returned to normal in 1 case, and only 1 patient did not improve. In the physiotherapy group, a slight improvement was noted in 6 patients and unchanged in four cases. From the questionnaires, patients underwent lymphatic TRAM/DIEP flap surgery reported a significantly greater improvement in the affected limb (p < 0.05). In the physiotherapy group, the limb subjective did not improve as well as in the surgery group. Lymphatic TRAM/DIEP is a safe and effective option for patients who suffer from post-mastectomy lymphoedema.

Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Krüppel-like factor 5 in triple-negative breast cancer.

PURPOSE: Dexamethasone (Dex), a glucocorticoid (GC), is used as a pretreatment drug in cancer patients undergoing chemotherapy. Dex functions by binding to the glucocorticoid receptor (GR) to prevent allergic reactions and severe chemotherapeutic side effects such as nausea and vomiting. However, the mechanisms by which Dex causes chemoresistance remain unknown. METHODS: We used docetaxel and cisplatin to treat triple-negative breast cancer (TNBC) cells with or without Dex and assessed cell proliferation using a sulforhodamine B colorimetric (SRB) assay. Additionally, Western blotting was employed to measure Krüppel-like factor 5 (KLF5), GR and several apoptosis-related proteins. To determine how the GR regulates KLF5, we used qRT-PCR, luciferase reporter assays and ChIP assays. Finally, we detected the involvement of Dex in TNBC chemotherapeutic resistance using HCC1806 xenograft model in vivo. RESULTS: In this study, we demonstrated that Dex induces docetaxel and cisplatin resistance in TNBC cells in vitro and in vivo. Dex up-regulates pro-survival transcription factor KLF5 expression at both mRNA and protein levels dependent on GR. Importantly, Dex failed to promote cancer cell survival and tumor growth when KLF5 induction was blocked. CONCLUSIONS: We conclude that KLF5 is a Dex-induced gene that contributes to Dex-mediated drug chemoresistance, providing a potential novel target for TNBC treatment.

The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene-Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients.

Folate-mediated one-carbon metabolism (FMOCM) is linked to DNA synthesis, methylation, and cell proliferation. Vitamin B6 (B6) is a cofactor, and genetic polymorphisms of related key enzymes, such as serine hydroxymethyltransferase (SHMT), methionine synthase reductase (MTRR), and methionine synthase (MS), in FMOCM may govern the bioavailability of metabolites and play important roles in the maintenance of genomic stability and cell viability (GSACV). To evaluate the influences of B6, genetic polymorphisms of these enzymes, and gene-nutrient interactions on GSACV, we utilized the cytokinesis-block micronucleus assay (CBMN) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques in the lymphocytes from female breast cancer cases and controls. GSACV showed a significantly positive correlation with B6 concentration, and 48 nmol/L of B6 was the most suitable concentration for maintaining GSACV in vitro. The GSACV indexes showed significantly different sensitivity to B6 deficiency between cases and controls; the B6 effect on the GSACV variance contribution of each index was significantly higher than that of genetic polymorphisms and the sample state (tumor state). SHMT C1420T mutations may reduce breast cancer susceptibility, whereas MTRR A66G and MS A2756G mutations may increase breast cancer susceptibility. The role of SHMT, MS, and MTRR genotype polymorphisms in GSACV is reduced compared with that of B6. The results appear to suggest that the long-term lack of B6 under these conditions may increase genetic damage and cell injury and that individuals with various genotypes have different sensitivities to B6 deficiency. FMOCM metabolic enzyme gene polymorphism may be related to breast cancer susceptibility to a certain extent due to the effect of other factors such as stress, hormones, cancer therapies, psychological conditions, and diet. Adequate B6 intake may be good for maintaining genome health and preventing breast cancer.

Comparison of Clinicopathological Features and Treatments between Young (≤40 Years) and Older (>40 Years) Female Breast Cancer Patients in West China: A Retrospective, Epidemiological, Multicenter, Case Only Study.

The incidence of young cases of breast cancer is higher in China compared to the western world. We aimed to explore differences in risk factors, clinicopathological features and treatment modes of young female breast cancer compared to older patients in West China. We collected clinical information from 12,209 female breast cancer patients in West China, including risk factors, clinicopathological features and treatment modes, from January 2010 to December 2012. Chi-square tests and the multivariate logistic regression analysis were applied for statistical analysis. There were 2,682 young (≤40 years) cases and 9,527 older cases at the time of breast cancer diagnosis. Young patients had a greater tumor diameter at diagnosis, and a higher probability of axillary lymph node and distant metastasis (P < 0.05). The progesterone receptor positive expression rate, estrogen receptor/progesterone receptor double positive expression rate, and human epidermal growth factor receptor 2 (HER2) negative expression rate was higher in young patients compared to older patients (P < 0.05). For young patients, the age at menarche was earlier, they had lower marriage rates, fewer pregnancies and births, and a lower breastfeeding rate (P < 0.05). A higher proportion of young patients underwent advanced operations, neoadjuvant and adjuvant chemotherapy, radiotherapy, and endocrine therapy compared to older patients (P < 0.05). We found significant differences in the clinicopathological features, risk factors and treatment modes between young (≤40 years) and older (>40 years) female breast cancer patients in West China. As some of these results differ from those found in the western female population, it is likely that the mechanism of tumorigenesis of young female breast cancer patients in West China may differ from that in western developed countries. Further investigation into the regional differences in breast cancer tumorigenesis is warranted.

Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Krüppel-like factor 5 (KLF5).

The Krüppel-like factor 5 (KLF5) has been suggested to promote breast cell proliferation, survival and tumorigenesis. KLF5 protein degradation is increased by several E3 ubiquitin ligases, including WWP1 and SCFFbw7, through the ubiquitin-proteasome pathway. However, the deubiquitinase (DUB) of KLF5 has not been demonstrated. In this study, we identified ATXN3L as a KLF5 DUB by genome-wide siRNA screening. ATXN3L directly binds to KLF5, decreasing its ubiquitination and thus degradation. Functionally, knockdown of ATXN3L inhibits breast cancer cell proliferation partially through KLF5. These findings reveal a previously unrecognized role of ATXN3L in the regulation of KLF5 stability in breast cancer. ATXN3L might be a therapeutic target for breast cancer.

WWOX suppresses KLF5 expression and breast cancer cell growth.

The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor in a variety of cancers, including breast cancer. Reduced WWOX expression is associated with the basal-like subtype and a relatively poor disease-free survival rate among breast cancer patients. Though several WWOX partners have been identified, the functional mechanisms of WWOX's role in cancers have not been fully addressed to date. In the current study, we found WWOX suppresses expression of KLF5-an oncogenic transcription factor-at protein level, and suppresses cancer cell proliferation in both bladder and breast cancer cell lines. Furthermore, we demonstrated that WWOX physically interacts with KLF5 via the former's WW domains and the latter's PY motifs. Interestingly, we found the expression of WWOX negatively correlates with KLF5 expression in a panel of breast cancer cell lines. Taken together, we conjecture that WWOX may suppress cancer cell proliferation partially by reducing the expression of KLF5.

Simultaneous breast reconstruction and treatment of breast cancer-related upper arm lymphedema with lymphatic lower abdominal flap.

BACKGROUND: This study was designed to introduce the key points about the transplantation of lower abdominal flap with vascularized lymph node and to evaluate the effect of breast restoration, breast reconstruction, and lymphatic transplantation to treat upper limb lymphedema after breast cancer surgery. MATERIALS AND METHODS: The study was based on the retrospective study on 10 cases of postmastectomy lymphedema during January 2008 to March 2011. All patients, aged 36 to 50 years, have had one-side upper-limb lymphedema for 3 to 5 years. Six patients had accepted radiotherapy. Four patients had a diagnosis of severe lymphedema, and 2 patients had moderate lymphedema. The isotope radiography before the operation showed obstruction of lymphatic return, and the multidetector computed tomography that followed delivered a clear picture of the abdominal flap blood supply and the blood vessels in the breasts. During the operation, the scar contracture of the axilla was completely relaxed, and all patients accepted abdominal transplantation of lower abdominal flap with vascularized lymph node. After the operation, the elastic bandages were applied for one year as an adjuvant therapy. The follow-up visits were conducted 1, 3, 6, and 12 months after the surgery. The measurement indexes included mid-upper arm circumference, clinical symptoms, and lymphoscintigraphy. RESULTS: All flaps worked well. One patient was found to have delayed wound healing; one patient saw no obvious improvement in lymphedema; 7 patients with lymphedema were relieved with apparent improvement in the affected limbs' mean perimeter and clinical symptoms; one patient recovered; and another patient was lost to follow-up. The mean reduction was 2.122±2.331 cm, and the reduction of the lymphedematous limb was statistically significant between the preoperative and 12-month postoperative groups (P<0.05). The results were good in 4 patients and excellent in one patient. CONCLUSIONS: The transplantation of abdominal flap with vascularized lymph node and breast reconstruction, accompanied by the treatment to upper limb lymphedema and using elastic bandages as an adjuvant therapy, is considered to be an effective method to restore the configuration and function of breasts. Long-term follow-up visits are undergoing, especially the lymphoscintigraphy, 2 years after the operation.

Plasma homocysteine levels and genetic polymorphisms in folate metablism are associated with breast cancer risk in chinese women.

BACKGROUND: Folate plays a pivotal role in DNA synthesis, repair, methylation and homocysteine (Hcy) metabolism. Therefore, alterations in the folate-mediated one-carbon metabolism may lead to abnormal methylation proliferation, increases of tumor/neoplasia and vein thrombosis/cardiovascular risk. The serine hydroxymethyhransferase (SHMT), methionine synthase (MS), methionine synthase reductase (MTRR) and cystathionine beta synthase (CBS) regulate key reactions in the folate and Hcy metabolism. Therefore, we investigated whether the genetic variants of the SHMT, MS, MTRR and CBS gene can affect plasma Hcy levels and are associated with breast cancer risk. METHODS: Genotyping was performed by PCR-RFLP method. Plasma Hcy levels were measured by the fluorescence polarization immunoassay on samples of 96 cases and 85 controls. RESULTS: (a) The SHMT 1420 T, MS 2756G, MTRR 66G allele frequency distribution showed significant difference between case and controls (p < 0.01 ~ 0.05). (b) The concentration of plasma Hcy levels of SHMT 1420TT was significantly lower than that of the wild type, while the plasma Hcy levels of MS 2756GG, CBS 699TT/1080TT significantly higher than that of the wild type both in case and controls. The plasma Hcy levels of MTRR 66GG was significantly higher than that of wild type in cases. The plasma Hcy levels of the same genotype in cases were significantly higher than those of controls except SHMT 1420CC, MS 2756AA, MTRR 66GG; (c) Multivariate Logistic regression analysis showed that SHMT C1420T (OR = 0.527, 95% CI = 0.55 ~ 1.24), MS A2756G (OR = 2.32, 95% CI = 0.29 ~ 0.82), MTRR A66G (OR = 1.84, 95% CI = 0.25 ~ 1.66) polymorphism is significantly associated with breast cancer risk. And elevated plasma Hcy levels were significantly linked to increased risk of breast cancer (adjusted OR = 4.45, 95% CI = 1.89-6.24 for the highest tertile as compared with the lowest tertile). CONCLUSIONS: The current study results seem to suggest a possibility that SHMT C1420T mutation may be negatively correlated with breast cancer susceptibility; while MS A2756G and MTRR A66G mutation may be positively associated with breast cancer risk. SHMT C1420T, MS A2756G, MTRR A66G, CBS C1080T, CBS C699T locus mutation may be factors affecting plasma levels of Hcy. The plasma Hcy levels could be metabolic risk factor for breast cancer risk to a certain extent.

Effects of folic acid deficiency and MTHFRC677T polymorphisms on cytotoxicity in human peripheral blood lymphocytes.

Apoptosis (APO) and necrosis (NEC) are two different types of cell death occurring in response to cellular stress factors. Cells with DNA damage may undergo APO or NEC. Folate is an essential micronutrient associated with DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) regulates intracellular folate metabolism. Folate deficiency and MTHFR C677T polymorphisms have been shown to be related to DNA damage. To verify the cytotoxic effects of folate deficiency on cells with different MTHFR C677T genotypes, 15 human peripheral lymphocyte cases with different MTHFR C677T genotypes were cultured in folic acid (FA)-deficient and -sufficient media for 9 days. Cytotoxicity was quantified using the frequencies of APO and NEC as endpoints, the nuclear division index (NDI), and the number of viable cells (NVC). These results showed that FA is an important factor in reducing cytotoxicity and increasing cell proliferation. Lymphocytes with the TT genotype proliferated easily under stress and exhibited different responses to FA deficiency than lymphocytes with the CC and CT genotypes. A TT individual may accumulate more cytotoxicity under cytotoxic stress, suggesting that the effects of FA deficiency on cytotoxicity are greater than the effects in individuals with the other MTHFR C677T variants.

Development and validation of the system of quality of life instruments for cancer patients: breast cancer (QLICP-BR).

GOALS: To develop and validate a quality of life (QOL) instrument for patients with breast cancer, QLICP-BR, which is one of the system of QOL instruments for cancer patients in China. METHODS: Using the programmed decision methods of instrument development, the quality of life instrument for cancer patients-breast cancer (QLICP-BR) with considering Chinese cultural background was developed, and evaluated on the data from 186 inpatients with breast cancer. The statistical methods used in this research included statistical description, Pearson correlation, factor analysis, and paired t test. RESULTS: The test-retest reliability for the overall scale and five domains are all above 0.75. Internal consistency alpha for each domain is higher than 0.65 except social domain (0.58). Most correlation coefficients between each item and it's domain are above 0.60. The scores differences between pretreatment and post-treatment for overall scale, general module, physical domain, psychological domain and social domain have statistical significance. CONCLUSIONS: The QLICP-BR is of good validity, reliability, and reasonable responsiveness, and can be used to assess quality of life for patients with breast cancer in China.

[Development of the system of quality of life instruments for patients with breast cancer (QLICP-BR)].

BACKGROUND & OBJECTIVE: The general module of the system of quality of life instruments for cancer patients, QLICP-GM, has been developed by us. Based on it, this study was to develop and evaluate the quality of life instrument for patients with breast cancer (QLICP-BR). METHODS: Using the structured group methods of instrument development, the instrument with Chinese cultural background was developed, and evaluated by analyzing the data from 186 breast cancer patients. RESULTS: The test-retest reliability for the overall scale and 5 domains were all above 0.75. The internal consistency alpha for each domain was higher than 0.65 except social domain (0.58). Most correlation coefficients between each item and the domain (that the item belongs to) were above 0.60. The differences between the scores before treatment and the scores after treatment for overall scale, general module, physical domain, psychologic domain, and social domain were significant. CONCLUSION: The QLICP-BR is of good validity, reliability and reasonable responsiveness, and can be used to assess quality of life for breast cancer patients.