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1.
Int J Cancer ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36093581

RESUMO

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly attributed to late diagnosis. We assessed the predictive performance of our previously reported urine biomarker panel for earlier detection of PDAC (LYVE1, REG1B, TFF1) in prediagnostic samples, alone and in combination with plasma CA19-9. This nested case-control study included 99 PDAC cases with urine samples prospectively collected up to 5 years prior to PDAC diagnosis and 198 matched controls. The samples were obtained from the Shanghai Women's Health Study (SWHS), the Shanghai Men's Health Studies (SMHS) and the Southern Community Cohort Study (SCCS). The urine biomarkers were measured by ELISA. Plasma CA19-9 was quantified by Luminex. Multiple logistic regression and Wilcoxon rank-sum and Mann-Whitney test were used for analysis. The internal validation approach was applied and the validated AUC estimators are reported on. The algorithm of urinary protein panel, urine creatinine and age named PancRISK, displayed similar AUC as CA19-9 up to 1 year before PDAC diagnosis (AUC=0.79), however the combination enhanced the AUCs to 0.89, and showed good discriminative ability (AUC=0.77) up to 2 years. The combination showed sensitivity (SN) of 72% at 90% specificity (SP), and SP of 59% at 90% SN up to 1 year and 60% SN with 80% SP and 53% SP with 80% SN up to 2 years before PDAC diagnosis. Adding the clinical information on BMI value resulted in the overall improvement in performance of the PancRISK score. When combined with CA19-9, the urinary panel reached a workable model for detecting PDAC cases up to 2 years prior to diagnosis.

2.
Cancer Biomark ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36093688

RESUMO

BACKGROUND: The clinicopathological significance of spatial tumor-infiltrating lymphocytes (TILs) subpopulations is not well studied due to lack of high-throughput scalable methodology for studies with large human sample sizes. OBJECTIVE: Establishing a cyclic fluorescent multiplex immunohistochemistry (mIHC/IF) method coupled with computer-assisted high-throughput quantitative analysis to evaluate associations of six TIL markers (CD3, CD8, CD20, CD56, FOXP3, and PD-L1) with clinicopathological factors of breast cancer. METHODS: Our 5-plex mIHC/IF staining was shown to be reliable and highly sensitive for labeling three biomarkers per tissue section. Through repetitive cycles of 5-plex mIHC/IF staining, more than 12 biomarkers could be detected per single tissue section. Using open-source software CellProfiler, the measurement pipelines were successfully developed for high-throughput multiplex evaluation of intratumoral and stromal TILs. RESULTS: In analyses of 188 breast cancer samples from the Nashville Breast Health Study, high-grade tumors showed significantly increased intratumoral CD3+CD8+ CTL density (P= 0.0008, false discovery rate (FDR) adjusted P= 0.0168) and intratumoral PD-L1 expression (P= 0.0061, FDR adjusted P= 0.0602) compared with low-grade tumors. CONCLUSIONS: The high- and low-grade breast cancers exhibit differential immune responses which may have clinical significances. The multiplexed imaging quantification strategies established in this study are reliable, cost-efficient and applicable in regular laboratory settings for high-throughput tissue biomarker studies, especially retrospective and population-based studies using archived paraffin tissues.

3.
J Nutr Sci ; 11: e62, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992572

RESUMO

The role of dietary factors in osteoporotic fractures (OFs) in women is not fully elucidated. We investigated the associations between incidence of OF and dietary calcium, magnesium and soy isoflavone intake in a longitudinal study of 48 584 postmenopausal women. Multivariable Cox regression was applied to derive hazard ratios (HRs) and 95 % confidence intervals (CIs) to evaluate associations between dietary intake, based on the averages of two assessments that took place with a median interval of 2⋅4 years, and fracture risk. The average age of study participants is 61⋅4 years (range 43⋅3-76⋅7 years) at study entry. During a median follow-up of 10⋅1 years, 4⋅3 % participants experienced OF. Compared with daily calcium intake ≤400 mg/d, higher calcium intake (>400 mg/d) was significantly associated with about a 40-50 % reduction of OF risk among women with a calcium/magnesium (Ca/Mg) intake ratio ≥1⋅7. Among women with prior fracture history, high soy isoflavone intake was associated with reduced OF risk; the HR was 0⋅72 (95 % CI 0⋅55, 0⋅93) for the highest (>42⋅0 mg/d) v. lowest (<18⋅7 mg/d) quartile intake. This inverse association was more evident among recently menopausal women (<10 years). No significant association between magnesium intake and OF risk was observed. Our findings provide novel information suggesting that the association of OF risk with dietary calcium intake was modified by Ca/Mg ratio, and soy isoflavone intake was modified by history of fractures and time since menopause. Our findings, if confirmed, can help to guide further dietary intervention strategies for OF prevention.


Assuntos
Isoflavonas , Fraturas por Osteoporose , Adulto , Cálcio , Cálcio na Dieta , Ingestão de Alimentos , Feminino , Humanos , Estudos Longitudinais , Magnésio , Fraturas por Osteoporose/prevenção & controle , Pós-Menopausa , Estudos Prospectivos
4.
Am J Clin Nutr ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36041172

RESUMO

BACKGROUND: Epidemiological studies suggest that coffee consumption may be inversely associated with risk of endometrial cancer (EC), the most common gynecological malignancy in developed countries. Furthermore, coffee consumption may lower circulating levels of estrogen and insulin, hormones implicated in endometrial carcinogenesis. Antioxidants and other chemopreventive compounds in coffee may have anticarcinogenic effects. Based on available meta-analyses, the World Cancer Research Fund concluded that consumption of coffee probably protects against EC. OBJECTIVE: Our main aim was to examine the association between coffee consumption and EC risk by combining individual-level data in a pooled analysis. We also sought to evaluate potential effect modification by other risk factors of EC. PATIENTS AND METHODS: We combined individual-level data from 19 epidemiologic studies (6 cohort, 13 case-control) of 12,159 endometrial cancer cases and 27,479 controls from the Epidemiology of Endometrial Cancer Consortium (E2C2). Logistic regression was used to calculate odds ratios (OR) and their corresponding 95% confidence intervals (CI). All models were adjusted for potential confounders including age, race, body mass index, smoking status, diabetes status, study design and study site. RESULTS: Coffee drinkers had a lower risk of EC compared to non-coffee drinkers (multi-adjusted OR = 0.87, 95% CI = 0.79,0.95). There was a dose-response relationship between higher coffee consumption and lower risk of EC: compared to non-coffee drinkers, the adjusted pooled ORs for those who drank 1, 2-3 and more than 4 cups/day were 0.90 (95% CI = 0.82,1.00), 0.86 (95% CI = 0.78,0.95), and 0.76 (95% CI = 0.66,0.87), respectively (p for trend < 0.001). The inverse association between coffee consumption and EC risk was stronger in participants with body mass index (BMI) over 25 kg/m2. CONCLUSION: The results of the largest analysis to date pooling individual-level data further support the potentially beneficial health effects of coffee consumption in relation to EC, especially among females with higher BMI.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36040947

RESUMO

OBJECTIVE: Predicting breast cancer survival and targeting patients at high-risk of mortality is of crucial importance. METHODS: We built a Bayesian Dynamic Cox (BDCox) model for predicting 5-year overall survival in breast cancer patients using data of the SEER Cancer Registry with 12,840 women diagnosed with infiltrating duct and lobular carcinoma breast cancer from 2010-2015. Four feature selection methods were used to identify predictors and enhance parsimony: fast backward variable selection, elastic net, Bayesian Model Average (BMA), and clinical expertise. All resulting models and a baseline full model containing all features were internally validated via bootstrapping and externally validated in the Shanghai Breast Cancer Survival Study. RESULTS: BMA outperformed other feature selection methods in both internal and external validations. The BDCox model with 12 predictors: chemotherapy, N Stage, T Stage, marital status, tumor malignancy, number of positive nodes, radiation, race, age, progesterone receptor, tumor grade, and estrogen receptor, had the best performance. Several predictors showed time-varying associations with survival that are in agreement with previous studies. CONCLUSION: The model developed using BDCox outperformed other prognostic models considered in our study. The internal validation results indicate that the BDCox model is capable of achieving high prediction accuracy (C-statistic: 0.802), and the external validation results showed excellent generalizability of the BDCox model (C-statistic: 0.739). SIGNIFICANCE: We built a dynamic Bayesian model from the large population-based registry SEER for predicting 5-year breast cancer overall survival. The prediction performance of the BDCox model is significantly better than other survival models.

6.
J Cancer Surviv ; 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35963975

RESUMO

PURPOSE: Chronic pain is a common symptom affecting quality of life for breast cancer survivors. However, its prevalence and correlate factors in long-term breast cancer survivors, particularly Asian women, are understudied. The reported study is to address these knowledge gaps. METHODS: We evaluated pain severity and frequency, and their associations with clinical features and lifestyle factors among 3640 5-year breast cancer survivors who participated in the Shanghai Breast Cancer Survival Study. Demographic, clinical, and lifestyle information was collected at study enrollment, which occurred 6 months post-diagnosis, and pain was assessed at the 5-year post-diagnosis follow-up survey. RESULTS: In total, 42% of participants reported experiencing pain. Pain is more prevalent among survivors with low educational attainment or low income. Multivariable polytomous regression analyses showed that pain was positively associated with metastasis or recurrence (moderate pain OR: 2.17, 95% CI: 1.45, 3.26, frequent pain OR: 1.92, 95% CI: 1.37, 2.70), triple negative status (infrequent pain OR: 1.36, 95% CI: 1.04, 1.78), obesity (frequent pain OR: 1.80, 95% CI: 1.41, 2.31), and multiple comorbidities. Exercise (OR: 0.65, 95%: 0.49, 0.88), chemotherapy (OR: 0.59, 95% CI: 0.41, 0.849), and HER2-positive and ER/PR-negative status (OR: 0.64, 95% CI: 0.43, 0.97) were inversely associated with moderate pain. CONCLUSIONS: Chronic pain is highly prevalent among long-term breast cancer survivors in China and was associated with obesity, physical inactivity, and several clinical factors. IMPLICATIONS FOR CANCER SURVIVORS: This study highlights the importance of promoting weight control and exercise to alleviate chronic pain.

7.
Cancers (Basel) ; 14(14)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35884451

RESUMO

Importance: The reasons underlying racial/ethnic mortality disparities for cancer patients remain poorly understood, especially regarding the role of access to care. Participants: Over five million patients with a primary diagnosis of lung, breast, prostate, colon/rectum, pancreas, ovary, or liver cancer during 2004-2014, were identified from the National Cancer Database. Cox proportional hazards models were applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for total mortality associated with race/ethnicity, and access to care related factors (i.e., socioeconomic status [SES], insurance, treating facility, and residential type) for each cancer. Results: Racial/ethnic disparities in total mortality were observed across seven cancers. Compared with non-Hispanic (NH)-white patients, NH-black patients with breast (HR = 1.27, 95% CI: 1.26 to 1.29), ovarian (HR = 1.20, 95% CI: 1.17 to 1.23), prostate (HR = 1.31, 95% CI: 1.30 to 1.33), colorectal (HR = 1.11, 95% CI: 1.10 to 1.12) or pancreatic (HR = 1.03, 95% CI: 1.02 to 1.05) cancers had significantly elevated mortality, while Asians (13-31%) and Hispanics (13-19%) had lower mortality for all cancers. Racial/ethnic disparities were observed across all strata of access to care related factors and modified by those factors. NH-black and NH-white disparities were most evident among patients with high SES or those with private insurance, while Hispanic/Asian versus NH-white disparities were more evident among patients with low SES or those with no/poor insurance. Conclusions and Relevance: Racial/ethnic mortality disparities for major cancers exist across all patient groups with different access to care levels. The influence of SES or insurance on mortality disparity follows different patterns for racial/ethnic minorities versus NH-whites. Impact: Our study highlights the need for racial/ethnic-specific strategies to reduce the mortality disparities for major cancers.

8.
Br J Cancer ; 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35882941

RESUMO

BACKGROUND: The aetiologic role of circulating proteins in the development of breast cancer subtypes is not clear. We aimed to examine the potential causal effects of circulating proteins on the risk of breast cancer by intrinsic-like subtypes within the Mendelian randomisation (MR) framework. METHODS: MR was performed using summary statistics from two sources: the INTERVAL protein quantitative trait loci (pQTL) Study (1890 circulating proteins and 3301 healthy individuals) and the Breast Cancer Association Consortium (BCAC; 106,278 invasive cases and 91,477 controls). The inverse-variance (IVW)-weighted method was used as the main analysis to evaluate the associations between genetically predicted proteins and the risk of five different intrinsic-like breast cancer subtypes and the weighted median MR method, the Egger regression, the MR-PRESSO, and the MRLocus method were performed as secondary analysis. RESULTS: We identified 98 unique proteins significantly associated with the risk of one or more subtypes (Benjamini-Hochberg false discovery rate < 0.05). Among them, 51 were potentially specific to luminal A-like subtype, 14 to luminal B/Her2-negative-like, 11 to triple negative, 3 to luminal B-like, and 2 to Her2-enriched-like breast cancer (ntotal = 81). Associations for three proteins (ICAM1, PLA2R1 and TXNDC12) showed evident heterogeneity across the subtypes. For example, higher levels of genetically predicted ICAM1 (per unit of increase) were associated with an increased risk of luminal B/HER2-negative-like cancer (OR = 1.06, 95% CI = 1.03-1.08, BH-FDR = 2.43 × 10-4) while inversely associated with triple-negative breast cancer with borderline significance (OR = 0.97, 95% CI = 0.95-0.99, BH-FDR = 0.065, Pheterogeneity < 0.005). CONCLUSIONS: Our study found potential causal associations with the risk of subtypes of breast cancer for 98 proteins. Associations of ICAM1, PLA2R1 and TXNDC12 varied substantially across the subtypes. The identified proteins may partly explain the heterogeneity in the aetiology of distinct subtypes of breast cancer and facilitate the personalised risk assessment of the malignancy.

9.
Front Oncol ; 12: 895479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814479

RESUMO

Background: Previous studies conducted among European and Asian decedents reported inverse associations of serum total bilirubin and albumin with lung cancer risk. Yet, no study has been conducted among African Americans or low-income European Americans. Methods: This study included 522 incident lung cancer cases and 979 matched controls nested in the Southern Community Cohort Study, a cohort of predominantly low-income African and European Americans. Serum levels of total bilirubin and albumin, collected up to 11 years prior to case diagnoses, were measured by a clinical chemistry analyzer. Conditional logistic regression models were applied to evaluate the associations of total bilirubin and albumin with lung cancer risk. Results: Overall, serum levels of total bilirubin (ORT3 vs. T1 = 0.96, 95% CI: 0.66-1.39) were not significantly associated with lung cancer risk. However, higher levels of serum total bilirubin were significantly associated with decreased risk of lung cancer among participants who were diagnosed within two years following sample collection (ORT3 vs. T1 = 0.36, 95% CI: 0.15-0.87) and among former/never smokers (ORT3 vs. T1 = 0.54, 95% CI: 0.32-0.93). Serum levels of albumin were significantly associated with decreased risk of lung cancer overall (ORT3 vs. T1 = 0.70, 95% CI: 0.50-0.98) and among African Americans (ORT3 vs. T1 = 0.62, 95% CI: 0.41-0.96), but not among European Americans. Conclusion: Our results indicate that in a low-income African American and European American population, serum levels of total bilirubin may be related to lung cancer progression and differ by smoking status. Meanwhile, the association of serum albumin levels with lung cancer risk may differ by race. Further studies are warranted to confirm these results.

10.
BMJ Open ; 12(7): e052630, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35788076

RESUMO

OBJECTIVES: This study aimed to examine the association of high-sensitivity C reactive protein (hsCRP) with mortality risk and the attenuated effect of non-communicable disease history (NCD history ) on the association. DESIGN: Prospective cohort study. SETTING: Health Examinees cohort. PARTICIPANTS: A total of 41 070 men and 81 011 women aged ≥40 years were involved (follow-up: 6.8 years). OUTCOME MEASURES: Data and cause of death occurring until 31 December 2015 were confirmed by death statistics from the National Statistical Office. We conducted advanced analysis after stratification by NCD history and sensitivity analysis after excluding death before 1 or 2 years from recruitment. Cox proportional hazard and restricted cubic spline models were used to assess the association. RESULTS: The association between serum hsCRP and risk of all-cause mortality was observed with strong linearity in both genders and was not influenced by NCD history . The association of serum hsCRP with risk of cancer mortality was not observed in women with NCD history , but the association with risk of cardiovascular disease (CVD) mortality was predominantly observed in men with NCD history . CONCLUSIONS: This study suggests a dose-response association of hsCRP with mortality risk, including cancer and CVD mortality, in Koreans with low serum hsCRP, although the association with cancer and CVD mortality risk could be influenced by gender and NCD history .


Assuntos
Doenças Cardiovasculares , Neoplasias , Doenças não Transmissíveis , Proteína C-Reativa/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
11.
Cancer Epidemiol Biomarkers Prev ; 31(9): 1727-1734, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-35793701

RESUMO

BACKGROUND: This study was performed to investigate the association between body mass index (BMI) and gastric cancer in East and Southeast Asia where most of gastric cancer is non-cardia gastric cancer. METHODS: On the basis of 8,997 gastric cancer cases among the Asia Cohort Consortium participants from China, Japan, Korea, and Singapore (N = 538,835), we assessed gastric cancer risk according to BMI by calculating hazard ratios (HR) and 95% confidence intervals (CI) using the Cox proportional hazard regression model. RESULTS: A U-shaped associations between BMI and gastric cancer risk were observed. Gastric cancer risks in underweight group (<18.5 kg/m2) and in obesity group (≥27.5 kg/m2) were higher than reference BMI group (23-24.9 kg/m2; HR, 1.15; 95% CI, 1.05-1.25 for underweight; HR, 1.12; 95% CI, 1.03-1.22 for obesity, respectively). The associations of underweight and obesity with gastric cancer risk were consistent in the analyses for non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer. No significant association of underweight and obesity with the risk of cardia gastric cancer, diffuse-type gastric cancer, and early-onset gastric cancer was observed. In addition, we found that the U-shaped association between BMI and gastric cancer risk remained in nonsmokers, while only underweight was related to increased gastric cancer risk in smokers. CONCLUSIONS: BMI has a U-shaped association with gastric cancer risk in East and Southeast Asian population, especially for the non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer. IMPACT: Future studies with consideration of anatomic location and histology of gastric cancer are needed to establish the association of underweight as well as obesity with gastric cancer risk.


Assuntos
Neoplasias Intestinais , Neoplasias Gástricas , Índice de Massa Corporal , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Magreza
12.
Cancers (Basel) ; 14(13)2022 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35805033

RESUMO

BACKGROUND: Proteomics-based technologies are emerging tools used for cancer biomarker discovery. Limited prospective studies have been conducted to evaluate the role of circulating proteins in colorectal cancer (CRC) development. METHODS: A two-stage case-control proteomics study nested in the Shanghai Women's Health Study was conducted. A total of 1104 circulating proteins were measured in the discovery phase, consisting of 100 incident CRC cases and 100 individually matched controls. An additional 60 case-control pairs were selected for validation. Protein profiling at both stages was completed using the Olink platforms. Conditional logistic regression was used to evaluate the associations between circulating proteins and CRC risk. The elastic net method was employed to develop a protein score for CRC risk. RESULTS: In the discovery set, 27 proteins showed a nominally significant association with CRC risk, among which 22 were positively and 5 were inversely associated. Six of the 27 protein markers were significantly associated with CRC risk in the validation set. In the analysis of pooled discovery and validation sets, odds ratios (ORs) per standard deviation (SD) increase in levels of these proteins were 1.54 (95% confidence interval (CI): 1.15-2.06) for CD79B; 1.71 (95% CI: 1.24-2.34) for DDR1; 2.04 (95% CI: 1.39-3.01) for EFNA4; 1.54 (95% CI: 1.16-2.02) for FLRT2; 2.09 (95% CI: 1.47-2.98) for LTA4H and 1.88 (95% CI: 1.35-2.62) for NCR1. Sensitivity analyses showed consistent associations for all proteins with the exclusion of cases diagnosed within the first two years after the cohort enrollment, except for CD79B. Furthermore, a five-protein score was developed based on the six proteins identified and showed significant associations with CRC risk in both discovery and validation sets (Discovery: OR1-SD = 2.46, 95% CI: 1.53-3.95; validation: OR1-SD = 4.16, 95% CI: 1.92-8.99). CONCLUSIONS: A panel of five protein markers was identified as potential biomarkers for CRC risk. Our findings provide novel insights into the etiology of CRC and may facilitate the risk assessment of the malignancy.

13.
Int J Cancer ; 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35765848

RESUMO

Several polygenic risk scores (PRSs) have been developed to predict the risk of colorectal cancer (CRC) in European descendants. We used genome-wide association study (GWAS) data from 22 702 cases and 212 486 controls of Asian ancestry to develop PRSs and validated them in two case-control studies (1454 Korean and 1736 Chinese). Eleven PRSs were derived using three approaches: GWAS-identified CRC risk SNPs, CRC risk variants identified through fine-mapping of known risk loci and genome-wide risk prediction algorithms. Logistic regression was used to estimate odds ratios (ORs) and area under the curve (AUC). PRS115-EAS , a PRS with 115 GWAS-reported risk variants derived from East-Asian data, validated significantly better than PRS115-EUR derived from European descendants. In the Korea validation set, OR per SD increase of PRS115-EAS was 1.63 (95% CI = 1.46-1.82; AUC = 0.63), compared with OR of 1.44 (95% CI = 1.29-1.60, AUC = 0.60) for PRS115-EUR . PRS115-EAS/EUR derived using meta-analysis results of both populations slightly improved the AUC to 0.64. Similar but weaker associations were found in the China validation set. Individuals among the highest 5% of PRS115-EAS/EUR have a 2.52-fold elevated CRC risk compared with the medium (41-60th) risk group and have a 12% to 20% risk of developing CRC by age 85. PRSs constructed using results from fine-mapping and genome-wide algorithms did not perform as well as PRS115-EAS and PRS115-EAS/EUR in risk prediction, possibly due to a small sample size. Our results indicate that CRC PRSs are promising in predicting CRC risk in East Asians and highlights the importance of using population-specific data to build CRC risk prediction models.

14.
Neurology ; 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697505

RESUMO

OBJECTIVE: While the importance of healthy lifestyles for preventing Alzheimer's disease and related dementias (ADRD) has been recognized, epidemiologic evidence remains limited for non-White or low-income individuals who bear disproportionate burdens of ADRD. This population-based cohort study aims to investigate associations of lifestyle factors, individually and together, with the risk of ADRD among socioeconomically disadvantaged Americans. METHODS: In the Southern Community Cohort Study, comprising two-thirds self-reported Black and primarily low-income Americans, we identified incident ADRD using claims data among participants enrolled in Medicare for at least 12 consecutive months after age 65. Five lifestyle factors-tobacco smoking, alcohol consumption, leisure-time physical activity (LTPA), sleep hours, and diet quality- were each scored 0 (unhealthy), 1 (intermediate), or 2 (healthy) based on health guidelines. A composite lifestyle score was created by summing all scores. Cox regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD, treating death as a competing risk. RESULTS: We identified 1,694 patients with newly diagnosed ADRD among 17,209 participants during a median follow-up of 4.0 years in claims data; the mean age at ADRD diagnosis was 74.0 years. Healthy lifestyles were individually associated with 11%-25% reduced risk of ADRD: multivariable-adjusted HR (95% CI) was 0.87 (0.76-0.99) for never vs. current smoking, 0.81 (0.72-0.92) for low-to-moderate vs. no alcohol consumption, 0.89 (0.77-1.03) for ≥150 minutes of moderate or ≥75 minutes of vigorous LTPA each week vs. none, 0.75 (0.64-0.87) for 7-9 hours vs. >9 hours of sleep, and 0.85 (0.75-0.96) for the highest vs. lowest tertiles of Healthy Eating Index. The composite lifestyle score showed a dose-response association with up to 36% reduced risk of ADRD: multivariable-adjusted HRs (95% CIs) across quartiles were 1 (ref), 0.88 (0.77-0.99), 0.79 (0.70-0.90), and 0.64 (0.55-0.74); p-trend<0.001. The beneficial associations were observed regardless of participants' sociodemographics (e.g., race, education, and income) and health conditions (e.g., history of cardiometabolic diseases and depression). CONCLUSION: Our findings support significant benefits of healthy lifestyles for ADRD prevention among socioeconomically disadvantaged Americans, suggesting that promoting healthy lifestyles and reducing barriers to lifestyle changes are crucial to tackling the growing burden and disparities posed by ADRD.

15.
Carcinogenesis ; 43(6): 538-546, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35605986

RESUMO

Helicobacter pylori infection has been suggested to be associated with lung cancer risk. However, information is lacking on whether the association differs by H. pylori antigen. We conducted a nested case-control study within the Southern Community Cohort Study, including 295 incident lung cancer cases and 295 controls. Helicobacter pylori multiplex serology assay was performed to detect antibodies to 15 H. pylori proteins. Conditional logistic regression was used to estimate odds ratios (ORs) and confidence intervals (95% CIs) after adjustment for covariates. Overall H. pylori+ was associated with a non-statistically significant increased risk of lung cancer (OR: 1.29; 95% CI: 0.85-1.95). Significant associations, however, were observed for H. pylori+ VacA+ (OR: 1.64; 95% CI: 1.02-2.62) and H. pylori+ Catalase+ (OR: 1.75; 95% CI: 1.11-2.77). The positive association of H. pylori+ Catalase+ with lung cancer risk was predominantly seen among African Americans (OR: 2.09; 95% CI: 1.11-3.95) but not European Americans (OR: 1.20; 95% CI: 0.56-2.54). Among participants who smoked ≥ 30 pack-years, overall H. pylori+ (OR: 1.85; 95% CI: 1.02-3.35), H. pylori+ CagA+ (OR: 2.77; 95% CI: 1.35-5.70), H. pylori+ VacA+ (OR: 2.53; 95% CI: 1.25-5.13) and H. pylori+ HP1564+ (OR: 2.01; 95% CI: 1.07-3.77) were associated with increased risk of lung cancer. Our study provides novel evidence that associations of H. pylori infection with lung cancer risk differ by H. pylori biomarker, may be more evident among African Americans and may be modified by smoking habits. Furthermore, studies are warranted to confirm our findings.


Assuntos
Infecções por Helicobacter , Neoplasias Pulmonares , Antígenos de Bactérias , Proteínas de Bactérias , Biomarcadores , Estudos de Casos e Controles , Catalase , Estudos de Coortes , Infecções por Helicobacter/complicações , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Fatores de Risco
16.
Breast Cancer ; 29(5): 869-879, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35543923

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) genes play critical roles in immune surveillance, an important defence against tumors. Imputing HLA genotypes from existing single-nucleotide polymorphism datasets is low-cost and efficient. We investigate the relevance of the major histocompatibility complex region in breast cancer susceptibility, using imputed class I and II HLA alleles, in 25,484 women of Asian ancestry. METHODS: A total of 12,901 breast cancer cases and 12,583 controls from 12 case-control studies were included in our pooled analysis. HLA imputation was performed using SNP2HLA on 10,886 quality-controlled variants within the 15-55 Mb region on chromosome 6. HLA alleles (n = 175) with info scores greater than 0.8 and frequencies greater than 0.01 were included (resolution at two-digit level: 71; four-digit level: 104). We studied the associations between HLA alleles and breast cancer risk using logistic regression, adjusting for population structure and age. Associations between HLA alleles and the risk of subtypes of breast cancer (ER-positive, ER-negative, HER2-positive, HER2-negative, early-stage, and late-stage) were examined. RESULTS: We did not observe associations between any HLA allele and breast cancer risk at P < 5e-8; the smallest p value was observed for HLA-C*12:03 (OR = 1.29, P = 1.08e-3). Ninety-five percent of the effect sizes (OR) observed were between 0.90 and 1.23. Similar results were observed when different subtypes of breast cancer were studied (95% of ORs were between 0.85 and 1.18). CONCLUSIONS: No imputed HLA allele was associated with breast cancer risk in our large Asian study. Direct measurement of HLA gene expressions may be required to further explore the associations between HLA genes and breast cancer risk.


Assuntos
Neoplasias da Mama , Antígenos HLA , Alelos , Asiáticos/genética , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA/genética , Humanos , Polimorfismo de Nucleotídeo Único
17.
J Am Heart Assoc ; 11(11): e024388, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35621206

RESUMO

Background Elevated plasma levels of alpha-aminoadipic acid (2-AAA) have been associated with the development of type 2 diabetes and atherosclerosis. However, the nature of the association remains unknown. Methods and Results We identified genetic determinants of plasma 2-AAA through meta-analysis of genome-wide association study data in 5456 individuals of European, African, and Asian ancestry from the Framingham Heart Study, Diabetes Prevention Program, Jackson Heart Study, and Shanghai Women's and Men's Health Studies. No single nucleotide polymorphisms reached genome-wide significance across all samples. However, the top associations from the meta-analysis included single-nucleotide polymorphisms in the known 2-AAA pathway gene DHTKD1, and single-nucleotide polymorphisms in genes involved in mitochondrial respiration (NDUFS4) and macrophage function (MSR1). We used a Mendelian randomization instrumental variable approach to evaluate relationships between 2-AAA and cardiometabolic phenotypes in large disease genome-wide association studies. Mendelian randomization identified a suggestive inverse association between increased 2-AAA and lower high-density lipoprotein cholesterol (P=0.005). We further characterized the genetically predicted relationship through measurement of plasma 2-AAA and high-density lipoprotein cholesterol in 2 separate samples of individuals with and without cardiometabolic disease (N=98), and confirmed a significant negative correlation between 2-AAA and high-density lipoprotein (rs=-0.53, P<0.0001). Conclusions 2-AAA levels in plasma may be regulated, in part, by common variants in genes involved in mitochondrial and macrophage function. Elevated plasma 2-AAA associates with reduced levels of high-density lipoprotein cholesterol. Further mechanistic studies are required to probe this as a possible mechanism linking 2-AAA to future cardiometabolic risk.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Ácido 2-Aminoadípico/genética , Aterosclerose/genética , China , HDL-Colesterol , LDL-Colesterol , Feminino , Estudo de Associação Genômica Ampla , Humanos , Complexo Cetoglutarato Desidrogenase/genética , Análise da Randomização Mendeliana , Nucleotídeos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Triglicerídeos
18.
JAMA Netw Open ; 5(5): e2214181, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35639382

RESUMO

Importance: Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited. Objective: To examine the association of marital status with total and cause-specific mortality. Design, Setting, and Participants: This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021. Exposures: Marital status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 623 140 participants (326 397 women [52.4%] and 296 743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123 264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years. Conclusions and Relevance: This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.


Assuntos
Estudos de Coortes , Ásia/epidemiologia , Causas de Morte , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Cancers (Basel) ; 14(10)2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35626036

RESUMO

Epidemiological evidence on tooth loss and lung cancer risk remains limited, especially for smoking-specific associations. To investigate the association between tooth loss and lung cancer risk by smoking status, we first analyzed data from the Shanghai Men's Health Study (n = 49,868) and the Shanghai Women's Health Study (n = 44,309). Cox regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer risk in relation to tooth loss. We also conducted a meta-analysis to summarize epidemiologic findings to date, incorporating results from the current study and six previously published studies. For 7.3 median follow-up years, 973 incident lung cancer cases (613 men and 360 women) were ascertained. After adjustment for major covariates, tooth loss was associated with an increased risk of lung cancer among men (HR [95% CI] for >10 teeth vs. none = 1.59 [1.21-2.11]) but not among women (0.86 [0.50-1.46]). The positive association was stronger among male current smokers (1.75 [1.26-2.45], p-interaction by smoking status = 0.04). In a meta-analysis incorporating 4052 lung cancer cases and 248,126 non-cases, tooth loss was associated with a 1.64-fold increased risk of developing lung cancer (relative risk [RR, 95% CI] for the uppermost with the lowest category = 1.64 [1.44-1.86]). The positive association was more evident among current smokers (1.86 [1.41-2.46]), but no significant associations were found among never or former smokers. Our findings suggest that tooth loss may be associated with an increased risk of lung cancer, and the association could be modified by smoking status.

20.
JNCI Cancer Spectr ; 6(2)2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35603841

RESUMO

BACKGROUND: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients. METHODS: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer-specific mortality after adjustment for major prognostic factors and lifetime smoking history. RESULTS: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer-specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer-specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer-specific mortality. CONCLUSIONS: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer.


Assuntos
Atividades de Lazer , Neoplasias Pulmonares , Exercício Físico , Humanos , Neoplasias Pulmonares/diagnóstico , Atividade Motora , Estudos Prospectivos , Estados Unidos/epidemiologia
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