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Background. The relationship between heart rate in CAD patients who underwent percutaneous coronary intervention (PCI) and had long-term outcomes over up to 10 years of follow-up has not been investigated. Methods. All patients were from the CORFCHD-PCI, a retrospective cohort study that included a total of 6050 CAD patients who underwent PCI from January 2008 to December 2016. One patient was excluded due to a lack of heart rate data. Ultimately, 6049 patients were enrolled. The primary outcome was long-term mortality after PCI. Results. Patients were divided into 5 groups according to heart rate quintiles: 1st quintile (heart rate <66 beats/min; n=1123), 2nd quintile (heart rate ≥66 beats/min to 72 beats/min; n=1010), 3rd quintile (heart rate ≥72 beats/min to 78 beats/min; n=1442), 4th quintile (heart rate ≥78 beats/min to 84 beats/min; n=1211), and 5th quintile (heart rate ≥84 beats/min; n=1263). After multivariate Cox regression analyses, the respective risks of ACM, CM, and MACEs were increased 79.1% (hazard risk (HR) = 1.791, 95% CI: 1.207–2.657, P=0.004), 56.9% (HR = 1.569, 95% CI: 1.019–2.416, P=0.041), and 25.5% (HR = 1.255, 95% CI: 0.990–1.590, P=0.060) in the 4th quintile and 98.7% (HR = 1.987, 95% CI: 1.344–2.937, P=0.001), 98.8% (HR = 1.988, 95% CI: 1.310–3.016, P<0.001), and 0.36.1% (HR = 1.361, 95% CI: 1.071–1.730, P=0.012) in the 5th quintile compared with those in the 1st quintile. Patients with a heart rate of ≥80 beats/min had 89.4%, 115.2%, and 39.1% increased risk of ACM, CM, and MACEs, respectively, compared to those patients with a heart rate of <80 beats/min. Conclusion. The present study indicated that the resting heart rate is an independent predictor of adverse long-term outcomes in CAD patients who underwent PCI. [ABSTRACT FROM AUTHOR]

Objectives Data regarding hypertension in elderly adults with chronic kidney disease ( CKD) remains limited. This study aimed to assess the epidemiological characteristics of hypertension in elderly adults with CKD using data from a nationwide survey. Design A nationwide, multicenter, cross-sectional study with a large sample. Setting The Survey of Prevalence, Awareness, and Treatment Rates in Chronic Kidney Disease Patients with Hypertension in China ( PATRIOTIC). Participants Participants in PATRIOTIC (aged ≥60; n = 2,414). Measurements Trained physicians measured blood pressure ( BP) using a standard protocol with a mercury sphygmomanometer at the time of admission. Results The prevalence, awareness, and treatment of hypertension in elderly adults with CKD were 82.0%, 90.7%, and 87.3%, respectively. The control of hypertension at BP less than 140/90 mmHg was 29.6% and at BP less than 130/80 mmHg it was 12.1%. No significant differences were noted in the prevalence, awareness, treatment, or control of hypertension in individuals with CKD divided into the age groups of 60 to 69, 70 to 79, and 80 and older ( P > .05). With increasing age, the proportion of isolated systolic hypertension in elderly adults with CKD with uncontrolled hypertension increased ( P = .02). Obesity ( P = .01), CKD Stages 4 and 5 ( P < .001), and concomitant diabetes mellitus ( P = .002) were significantly associated with uncontrolled hypertension in elderly adults with CKD, using the goal of BP less than 140/90 mmHg. Conclusion The prevalence of hypertension in elderly adults in China with CKD is high, and its control is poor. Most elderly adults with CKD with uncontrolled hypertension have systolic hypertension. Obesity, CKD Stages 4 and 5, and diabetes mellitus were adversely associated with greater uncontrolled hypertension in elderly adults with CKD. [ABSTRACT FROM AUTHOR]

Objective: Although some studies have linked smoking to mortality after out-of-hospital cardiac arrests (OHCAs), data regarding smoking and mortality after OHCAs have not yet been discussed in a meta-analysis. Thus, this study conducted this systematic review to clarify the association. Methods: The study searched Medline-PubMed, Web of Science, Embase and Cochrane libraries between January 1972 and July 2022 for studies that evaluated the association between smoking and mortality after OHCAs. Studies that reportedly showed relative risk estimates with 95% confidence intervals (CIs) were included. Results: Incorporating a collective of five studies comprising 2477 participants, the analysis revealed a lower mortality risk among smokers in the aftermath of OHCAs compared with non-smokers (odds ratio: 0.77; 95% CI 0.61–0.96; P < 0.05). Egger's test showed no publication bias in the relationship between smoking and mortality after OHCAs. Conclusions: After experiencing OHCAs, smokers had lower mortality than non-smokers. However, due to the lack of data, this 'smoker's paradox' still needs other covariate effects and further studies to be considered valid. [ABSTRACT FROM AUTHOR]

Background. Coronary heart disease (CHD) is caused by the blockage or spasm of coronary arteries. Evidence shows that liver disease is related to CHD. However, the correlation between the Model for End-Stage Liver Disease (MELD) score and outcomes in patients after percutaneous coronary intervention (PCI) was unclear. Method. A retrospective cohort study involved 5373 patients with coronary heart disease after PCI was conducted from January 2008 to December 2016. Participants were classified to four groups according to the MELD score by quartiles. The primary endpoint was long-term mortality including all-case mortality (ACM) and cardiac mortality (CM). Secondary endpoints included bleeding events, readmission, major adverse cardiovascular events (MACE), major adverse cardiovascular, and cerebrovascular events (MACCE). The longest follow-up time was almost 10 years. Results. There were significant differences in the incidences of ACM (p = 0.038) and CM (p = 0.027) among the four MELD groups, but there was no significant difference in MACEs (p = 0.496), MACCEs (p = 0.234), readmission (p = 0.684), and bleeding events (p = 0.232). After adjusting the age, gender, smoking, drinking status, and diabetes by a multivariable Cox regression analysis, MELD remains independently associated with ACM (HR:1.57, 95%CI 1.052–2.354, p = 0.027) and CM (HR:1.434, 95% CI 1.003–2.050, p = 0.048). Conclusion. This study indicated that the MELD score had a strong prediction for long-term mortality in CHD patients who underwent PCI. [ABSTRACT FROM AUTHOR]

Background: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. Methods: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). Results: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60–70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892–0.984 (P = 0.009), 0.971–0.993 (P = 0.002), 0.967–0.999 (P = 0.033), and 0.958–0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938–1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. Conclusions: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly. [ABSTRACT FROM AUTHOR]

Background. In-stent restenosis (ISR) remains a common problem following percutaneous coronary intervention (PCI). However, the best treatment strategy remains uncertain. There is some controversy over the efficacy of drug-eluting balloons (DEBs) and second-generation drug-eluting stents (DESs) for treating ISR. Methods. A meta-analysis was used to compare the efficacy of the DEB and second-generation DES in the treatment of ISR. The primary endpoint is the incidence of target lesion revascularization (TLR). The secondary endpoint is the occurrence of target vessel revascularization (TVR), myocardial infarction (MI), all-cause death (ACM), cardiac death (CD), major adverse cardiac events (MACEs), minimum luminal diameter (MLD), late luminal loss (LLL), binary restenosis (BR), and percent diameter stenosis (DS%). Results. A total of 12 studies (4 randomized controlled trials and 8 observational studies) including 2020 patients with a follow-up of 6–25 months were included in the present study. There was a significant difference in the MLD between the two groups during follow-up (P=0.007, RR = 0.23, and 95% CI: 0.06–0.4 mm). There was no significant difference in LLL, BR, or DS% and the overall incidence of MACEs between the two groups. Subgroup analysis showed no significant difference in the incidence of primary and secondary endpoints when considering RCTs or observational studies only. Conclusions. The efficacy of the DEB and second-generation DES in the treatment of ISR is comparable. However, our results need further verification through multicenter randomized controlled trials. [ABSTRACT FROM AUTHOR]

Purpose: To assess the influence of factors related to migration and acculturation on myopia in migrant Indians in Singapore. Design: Population-based cross-sectional study. Methods: A total of 3400 Singaporean Indians (75.6% response rate) aged over 40 years participated in this study. Information regarding country of birth, migration age, and language of interview were collected from interviews. Indians born outside of Singapore were defined as “first-generation” immigrants, while Indians born in Singapore were defined as “second-generation (or higher)” immigrants. Refraction was determined by autorefraction and refined by subjective refraction. Ocular biometry including axial length (AL), anterior chamber depth (ACD), and corneal radius (CR) were measured by partial coherence interferometry. Myopia and high myopia were defined as spherical equivalents (SE) of less than −0.5 diopter (D) for myopia, and < −5 D for high myopia, respectively. Results: The prevalence of myopia (30.2% vs 23.4 %) and high myopia (4.8% vs 2.5%) were higher in second-generation immigrants compared with first-generation immigrants. Second-generation immigrants had longer AL (23.50 mm vs 23.37 mm, P = .004) than first-generation immigrants after multivariate adjustment. The excess prevalence of myopia was reduced by 37.5% but remained statistically significant (P = .02) after further controlling for educational level. Among first-generation immigrants, those migrating to Singapore before the age of 21 had significantly higher prevalence of myopia (odds ratio [OR]: 1.85; 95% confidence interval [CI]: 1.32, 2.59) and longer AL (regression coefficient: 0.27; 95% CI: 0.11, 0.43) than those migrating after 21 years of age. Also, first-generation immigrants interviewed in English had higher prevalence of myopia (OR: 1.46; 95% CI: 1.00, 2.17) than their non-English-interviewed counterparts. Conclusions: The prevalence of myopia among second-generation (or higher) Indian immigrants in Singapore is higher than first-generation immigrants. Country-specific environmental factors may be important for the increasing prevalence of myopia in Asia. [Copyright &y& Elsevier]

Objective. It is not clear which Traditional Chinese Medicine- (TCM-) related elements affect primary IgA nephropathy (IgAN) progression. Here, we explored the risk factors, based on TCM syndrome elements, related to the prognosis of primary IgAN patients. Methods. We analyzed patients with newly diagnosed, biopsy-proven IgAN at a single institution from December 2013 to September 2021. Basic clinical and pathological characteristics were assessed at the time of renal biopsy. The study endpoint was end-stage renal disease (ESRD: eGFR <15 ml/min per 1.73 m2, dialysis, or kidney transplantation) and/or eGFR decreased by >30% from baseline. Kaplan‒Meier survival analysis was used to explore the role of TCM syndrome elements in IgAN progression. Multivariate Cox regression analysis with adjustment for traditional risk factors was performed to explore TCM syndrome elements that may influence patient prognosis. The factors correlated with TCM syndrome elements in IgAN patients were further evaluated by logistic regression analysis. Results. During a median follow-up of 22.0 months, 53 (12.5%) of the 423 included IgAN patients reached the study endpoint. The main IgAN disease location elements were the kidney, liver, and spleen. The main IgAN disease nature elements were Yin-deficiency and Qi-deficiency, dampness, Yang-deficiency, phlegm, and Blood-deficiency. Kaplan‒Meier analysis identified three disease locations (liver, spleen, and kidney) and four disease natures (Qi-deficiency, Yang-deficiency, phlegm, and dampness) as elements associated with poor renal survival in IgAN patients. In multivariate Cox regression analysis, baseline Yang-deficiency was an independent risk predictor of poor prognosis in primary IgAN patients (hazard ratio 2.338; 95% confidence interval [CI]: 1.208–4.525; P = 0.012) after adjustment for traditional risk factors. Furthermore, logistic regression analysis identified being female (odds ratio [OR] 2.518; 95% CI: 1.538–4.122; P < 0.001), older age (OR 1.043; 95% CI: 1.022–1.065; P < 0.001), low hemoglobin levels (OR 0.984; 95% CI: 0.971–0.996; P = 0.013), and cellular/fibrocellular crescents (OR 1.706; 95% CI: 1.068–2.728; P = 0.026) as factors affecting Yang-deficiency in IgAN patients. Conclusions. Yang-deficiency independently predicts the risk of poor prognosis in primary IgAN patients. Being female, older age, low hemoglobin levels, and cellular/fibrocellular crescents were independently associated with Yang-deficiency in IgAN patients. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have suggested an association between the polymorphisms AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val and endometriosis, but results have been inconclusive. The aim of the present study was to assess these associations by meta-analysis. Methods: Eligible literatures were retrieved from PubMed, ISI Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were calculated with a random or fixed-effect model. Results: A total of six eligible studies were included. Regarding the AhR Arg554Lys and ARNT Val189Val polymorphisms, no obvious associations were found in either overall analysis or subgroup analysis based on the country, source of control, sample size, and genotyping method. For the AhRR Pro185Ala polymorphism, overall results suggested a marginal association with endometriosis susceptibility under the dominant model (OR = 1.65, 95 % CI = 1.00-2.72). Furthermore, a significantly increased risk for endometriosis was found in the subgroups which used the TaqMan method for genotype analysis or had a sample size ≥200. Conclusions: This meta-analysis suggested that the polymorphisms of AhR Arg554Lys and ARNT Val189Val are not associated with endometriosis, while the AhRR Pro185Ala polymorphism may be associated with endometriosis risk. However, further case-control studies with larger sample sizes are needed to confirm our results. [ABSTRACT FROM AUTHOR]

The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by the hormone receptor status of tumors among Chinese women. The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996–1998 (phase I) and 2002–2005 (phase II); 2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models. Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67–0.95; P trend = 0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend < 0.05), whereas intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the 4 tumor subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, whereas high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status. [ABSTRACT FROM PUBLISHER]

Background: Little is known about the prognostic advantage of sex for pulmonary adenocarcinoma among Chinese patients. In this study, we aimed to investigate the true sex differences in prognosis by adjusting for confounders and to explore whether the differences were time‐varying. Methods: We identified 4438 lung adenocarcinoma patients who underwent surgery at a regional Cancer Center of China from 2008 to 2016, retrospectively. Sex, age group, smoking history, year of diagnosis and pathological stage were collected. Time‐dependent Cox regression models with inverse probability of treatment weighting (IPTW) based on propensity score were used to assess the effect of sex and account for confounders. Landmark analyses were conducted to assess survival before, and after, five years. Results: Of these patients, 1761 (39.7%) were men and 2677 (60.3%) were women. Median follow‐up time was 52.6 months. After IPTW adjustment, women were found to have significantly better survival than men varying with time in both crude and IPTW models (hazard ratio [HR] [t] = 0.453*1.015t, where t is the length of time from treatment and its unit is month, p < 0.001). Women had significantly better survival than men within 0–5 years after surgery (HR = 0.763, 95% CI: 0.649–0.897, p = 0.001), whereas there was no difference after five years (HR = 1.135, 95% CI: 0.803–1.605, p = 0.472). In subgroup analysis, women in the 61–71+ age group, in the more than 20 year packs group, pathological stage 0–IB group, and 2013–2016 diagnosis period group revealed the same prognostic pattern. Conclusions: Compared with men, women had better survival after surgical resection of lung adenocarcinoma, especially those who were older and nonsmokers or heavy‐smokers and were pathological stage 0–IB in early years, while the advantage for women diminished with time. [ABSTRACT FROM AUTHOR]

We aimed to determine whether treatment effect size differed between randomised controlled phase II trials and subsequent phase III trials and examine potential predictor of positive phase III trials. We searched MEDLINE for randomised controlled phase II studies published from January 2006 to December 2015. Matched phase III trials that investigated same intervention in the same setting of the same cancer were identified through Web of Science, ClinicalTrials.gov and conference proceedings. For each pair of phase II and phase III trials, we extracted hazard ratios (HRs) with 95% confidence intervals (CIs) for both overall survival (OS) and progression-free survival (PFS) and evaluated the differences by ratio of HRs (rHRs): the HR for phase II trial to that for phase III trial. A summary rHR was obtained through a random-effect meta-analysis. Univariable analyses were conducted to identify predictors of positive phase III trials. We identified 57 pairs of phase II and phase III trials. Compared with phase III trials, treatment effect sizes of PFS were, on average, 26% larger in phase II trials (rHR = 0.74, P < 0.001, 95% CI: 0.68–0.80). Treatment effect sizes of OS were 27% greater in phase II trials than in phase III trials (rHR = 0.73, P < 0.001, 95% CI: 0.66–0.79). Fifteen (26.3%) phase III trials were positive, and the only predictor of positive phase III trials was positive phase II trials Treatment effects in randomised controlled phase II trials were greater than those in matched phase III trials. Caution must be taken when interpreting promising results from randomised controlled phase II trials. • Progression-free survival benefit was 26% larger in phase II than phase III trial. • Overall survival benefits was 27% larger in phase II than phase III trial. • The only predictor of positive phase III trials was positive phase II trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumors of head and neck cancer are a heterogenous collection of malignancies affecting the upper aerodigestive tract, the majority of which are head and neck squamous cell carcinomas (HNSCCs). Development of immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HNSCCs, albeit only in a minority of patients. Due to the low clinical response rates for HNSCCs and the potential for immune-related adverse side effects, predictive biomarkers are necessary to characterize patients who are most likely to respond to treatment. Previous studies have indicated that patient nutritional status may impact immune response. However, the effects of pretreatment nutritional status, specifically on immunotherapy-treated HNSCC patients, remains unclear. The aim of our study is to explore the associations between baseline prognostic nutritional index and pretreatment body mass index trends on the outcomes of HNSCC patients treated with anti-PD-1 or anti-CTLA-4 immunotherapy, or both. The association between pretreatment nutritional status and immunotherapy response in patients with advanced head and neck cancer is unclear. We retrospectively analyzed a cohort of 99 patients who underwent treatment with anti-PD-1 or anti-CTLA-4 antibodies (or both) for stage IV HNSCC between 2014 and 2020 at the Johns Hopkins Hospital. Patient demographics and clinical characteristics were retrieved from electronic medical records. Baseline prognostic nutritional index (PNI) scores and pretreatment body mass index (BMI) trends were calculated. Associations between PNI and BMI were correlated with overall survival (OS), progression-free survival (PFS), and immunotherapy response. In univariate analysis, there was a significant correlation between OS and PFS with baseline PNI (OS: HR: 0.464; 95% CI: 0.265–0.814; PFS: p = 0.007 and HR: 0.525; 95% CI: 0.341–0.808; p = 0.003). Poor OS was also associated with a greater decrease in pretreatment BMI trend (HR: 0.42; 95% CI: 0.229–0.77; p = 0.005). In multivariate analysis, baseline PNI but not BMI trend was significantly associated with OS and PFS (OS: log (HR) = −0.79, CI: −1.6, −0.03, p = 0.041; PFS: log (HR) = −0.78, CI: −1.4, −0.18, p = 0.011). In conclusion, poor pretreatment nutritional status is associated with negative post-immunotherapy outcomes. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have identified approximately 20 susceptibility loci for breast cancer. A cumulative genetic risk score (GRS) was constructed from 10 variants with replicated associations among participants of the Shanghai Breast Cancer Genetics Study (Shanghai, China, 1996–1998 and 2002–2005). Interactions between the GRS and 11 breast cancer risk factors were evaluated. Among the 6,408 study participants, no evidence of effect modification was found with the GRS for age at menarche, age at menopause, age at first live birth/parity, total months of breastfeeding, family history of breast cancer, history of benign breast disease, hormone replacement therapy, body mass index, waist/hip ratio, or regular physical activity. The effect of the GRS was least homogeneous by duration of menstruation; further analysis indicated a nominally significant interaction with one genetic variant. The mitochondrial ribosomal protein S30 gene (MRPS30) rs10941679 was associated with breast cancer risk only among women with more than 30 years of menstruation (odds ratio = 1.15, 95% confidence interval: 1.05, 1.26). Although this multiplicative interaction reached a nominal significance level (P = 0.037), it did not withstand correction for multiple comparisons. In conclusion, this study revealed no apparent interactions between genome-wide association study-identified genetic variants and breast cancer risk factors in the etiology of this common cancer.Abbreviations: CI, confidence interval; GRS, genetic risk score; OR, odds ratio; SNP, single nucleotide polymorphism. [ABSTRACT FROM PUBLISHER]

Purpose: Nine previously reported associations between single nucleotide polymorphisms (SNPs) and breast cancer outcomes from the Shanghai Breast Cancer Study (Stage 1) were further evaluated in relation to disease-free survival (DFS) and overall survival (OS) among 5,192 additional breast cancer patients (Stage 2). Methods: Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by proportional hazards regression in models adjusted for age, disease stage, estrogen and progesterone receptor status, and treatment regimens. Results: Two SNPs had generally consistent results and significant associations with OS in combined analyses. Compared to women with MMP7 rs11225297 AA genotypes, OS was moderately better for women with AT genotypes (HR: 0.8, 95% CI: 0.7-1.0) and much better for women with TT genotypes (HR: 0.4, 95% CI: 0.2-0.8). Compared to women with MMP8 rs11225395 CC genotypes, OS was slightly better for women with CT genotypes (HR: 0.9, 95% CI: 0.7-1.1) and moderately better for women with TT genotypes (HR: 0.6, 95% CI: 0.4-0.9). Joint analysis showed significant dose-response relationships with increasing numbers of rare alleles for both OS ( p < 0.001) and DFS ( p = 0.001). Conclusions: A functional variant in MMP8 and a SNP in high linkage disequilibrium with a functional variant in MMP7 were significantly associated with breast cancer survival in a large two-stage survival study among Chinese women. This supports the hypothesis that SNPs in matrix metalloproteinase genes may influence breast cancer prognosis; additional research on these and other SNPs in genes important in metastasis, angiogenesis, and the regulation of the tumor microenvironment is warranted. [ABSTRACT FROM AUTHOR]

Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER−)/PR-negative (PR−) cases, 301 ER+/PR− cases, 254 ER−/PR+ cases, and 3,474 controls aged 20–70 years in Shanghai, China (phase I, 1996–1998; phase II, 2002–2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)2) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER−/PR− subtype (for parity, Pheterogeneity = 0.02; for BMI, Pheterogeneity < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR− subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR− tumors and ER−/PR+ tumors. [ABSTRACT FROM PUBLISHER]

In previous studies among 1,144 cases and 1,256 controls recruited in stage 1 of the Shanghai Breast Cancer Study (SBCS I; 1996–1998), 18 known or potentially functional single nucleotide polymorphisms (SNPs) in 16 genes were found to be associated with breast cancer risk. The authors evaluated these associations among 1,918 cases and 1,819 controls recruited in stage 2 of the SBCS (SBCS II; 2002–2005) using genetic effect models and subgroup analyses predetermined from SBCS I results. Five SNPs (AHR rs2066853, ATM rs1003623, ESR1 rs2234693, GSTP1 rs1695, and SHBG rs6259) showed generally consistent results in SBCS I and SBCS II and statistically significant associations with breast cancer risk in combined analyses, mostly in subgroups defined by age or menopausal status. Further, the relation between breast cancer risk and SHBG rs6259 was found to vary by body mass index (weight (kg)/height (m)2) (P for interaction = 0.003). The strongest reduction in risk associated with SHBG rs6259 was found for lean (body mass index <23) postmenopausal minor allele carriers (odds ratio = 0.6, 95% confidence interval: 0.5, 0.8; P = 4.6 × 10−4). This biologically plausible and highly significant finding provides strong evidence for a true association among Asian women. This study also highlights the value of gene-environment interaction analyses in evaluating genetic factors for complex diseases. [ABSTRACT FROM PUBLISHER]

The fibroblast growth factor receptor 2 gene (FGFR2) has been associated with the risk of breast cancer in multiple ethnic populations, and its effect has been suggested to be hormone-dependent. A large, 2-stage, population-based case-control study was conducted in urban Shanghai, China, during the periods of 1996–1998 and 2002–2005. Exposure and genotyping information from 2,073 patients with breast cancer and 2,084 age-matched population controls was available for evaluation of the interactions between FGFR2 polymorphisms and exogenous estrogen exposure in the development of breast cancer. A logistic regression model was used to compute adjusted odds ratios and 95% confidence intervals. Of 20 genotyped and 25 imputed single nucleotide polymorphisms (SNPs), 22 were significantly associated with breast cancer. Three genotyped SNPs in close linkage disequilibrium, rs2303568, rs3135730, and rs1078806, and an imputed SNP of rs755793 in complete linkage disequilibrium with other 8 SNPs were observed to interact significantly with oral contraceptive (OC) use. The SNP-cancer association was evident only among OC users, and the OC use was only associated with the risk of breast cancer among carriers of these minor alleles at these loci. These findings suggest that genetic variants in FGFR2 may modify the role of OC use in causing breast cancer in Chinese women. [ABSTRACT FROM PUBLISHER]