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1.
Int J Cancer ; 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33521947

RESUMO

Family history (FH) of ovarian cancer and breast cancer are well-established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first- and second-degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high-grade serous vs others). First-degree FH of ovarian cancer was associated with high-grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First-degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high-grade serous carcinoma only in white women. Associations with second-degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high-grade serous carcinoma in both groups. First-degree FH of ovarian cancer and of breast cancer, and second-degree FH of ovarian cancer is strongly associated with high-grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high-grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.

2.
Aging (Albany NY) ; 13(2): 1692-1717, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468709

RESUMO

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

3.
Br J Nutr ; : 1-9, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33441193

RESUMO

High-quality diets have been found to be beneficial in preventing long-term weight gain. However, concurrent changes in diet quality and body weight over time have rarely been reported. We examined the association between 10-year changes in diet quality and body weight in the Multiethnic Cohort Study. Analyses included 53 977 African Americans, Native Hawaiians, Japanese Americans, Latinos and Whites, who completed both baseline (1993-1996, 45-69 years) and 10-year follow-up (2003-2008) surveys including a FFQ and had no history of heart disease or cancer. Using multivariable regression, weight changes were regressed on changes in four diet quality indexes, Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet and Dietary Approaches to Stop Hypertension scores. Mean weight change over 10 years was 1·2 (sd 6·8) kg in men and 1·5 (sd 7·2) kg in women. Compared with stable diet quality (< 0·5 sd change), the greatest increase (≥ 1 sd increase) in the diet scores was associated with less weight gain (by 0·55-1·17 kg in men and 0·62-1·31 kg in women). Smaller weight gain with improvement in diet quality was found in most subgroups by race/ethnicity, baseline age and baseline BMI. The inverse association was stronger in younger age and higher BMI groups. Ten-year improvement in diet quality was associated with a smaller weight gain, which varied by race/ethnicity and baseline age and BMI. Our findings suggest that maintaining a high-quality diet and improving diet quality over time may prevent excessive weight gain.

4.
Int J Cancer ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33105052

RESUMO

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

5.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2010-2018, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732252

RESUMO

BACKGROUND: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. METHODS: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. RESULTS: Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. CONCLUSIONS: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. IMPACT: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

6.
Curr Dev Nutr ; 4(3): nzaa024, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32190810

RESUMO

Background: Epidemiological data on the role of overall dietary patterns in nonalcoholic fatty liver disease (NAFLD) are limited, especially from population-based prospective studies. Objectives: We investigated the associations between dietary patterns assessed by predefined diet quality indexes (DQIs) and NAFLD risk by cirrhosis status in African Americans, Japanese Americans, Latinos, Native Hawaiians, and whites from the Multiethnic Cohort (MEC). Methods: A nested case-control analysis was conducted within the MEC. NAFLD cases were identified by linkage to 1999-2016 Medicare claims. Four DQIs-Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean diet score, and Dietary Approaches to Stop Hypertension (DASH) score-were calculated from a validated FFQ administered at baseline. Conditional logistic regression was used to estimate the ORs and 95% CIs with adjustment for multiple covariates. Results: Analyses included 2959 NAFLD cases (509 with cirrhosis; 2450 without cirrhosis) and 29,292 matched controls. Higher scores for HEI-2015 (i.e., highest compared with lowest quintile OR: 0.83; 95% CI: 0.73, 0.94; P for trend = 0.002) and DASH (OR: 0.78; 95% CI: 0.69, 0.89; P for trend < 0.001), reflecting favorable adherence to a healthful diet, were inversely associated with NAFLD risk. Whereas there were no differences by sex or race/ethnicity, the inverse association was stronger for NAFLD with cirrhosis than for NAFLD without cirrhosis (P for heterogeneity = 0.03 for HEI-2015 and 0.05 for DASH). Conclusions: Higher HEI-2015 and DASH scores were inversely associated with NAFLD risk in this ethnically diverse population. The findings suggest that having better diet quality may reduce NAFLD risk with more benefit to NAFLD with cirrhosis.

7.
JNCI Cancer Spectr ; 4(2): pkz107, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32211584

RESUMO

Background: There are increasing concerns about the potential impact of air pollution on chronic brain inflammation and microglia cell activation, but evidence of its carcinogenic effects is limited. Methods: We used kriging interpolation and land use regression models to estimate long-term air pollutant exposures of oxides of nitrogen (NOx, NO2), kriging interpolation for ozone (O3), carbon monoxide, and particulate matter (PM2.5, PM10), and nearest monitoring station measurements for benzene for 103 308 men and women from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993-1996) through 2013. We used Cox proportional hazards models to examine the associations between time-varying pollutants and risk of malignant brain cancer (94 men, 116 women) and meningioma (130 men, 425 women) with adjustment for sex, race and ethnicity, neighborhood socioeconomic status, smoking, occupation, and other covariates. Stratified analyses were conducted by sex and race and ethnicity. Results: Brain cancer risk in men increased in association with exposure to benzene (hazard ratio [HR] = 3.52, 95% confidence interval [CI] = 1.55 to 7.55) and PM10 (HR = 1.80, 95% CI = 1.00 to 3.23). Stronger associations with PM10 (HR = 3.02, 95% CI = 1.26 to 7.23), O3 (HR = 2.93, 95% CI = 1.09 to 7.88), and benzene (HR = 4.06, 95% CI = 1.17 to 18.2) were observed among Latino men. Air pollution was unrelated to risk of meningioma except that O3 exposure was associated with risk in men (HR = 1.77, 95% CI = 1.02 to 3.06). Brain cancer risk in women was unrelated to air pollution exposures. Conclusions: Confirmation of these sex differences in air pollution-brain cancer associations and the stronger findings in Latino men in additional diverse populations is warranted.

8.
Cancer Res ; 80(5): 1210-1218, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31932455

RESUMO

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.


Assuntos
Neoplasias Ovarianas/epidemiologia , Ovário/imunologia , Ovulação/imunologia , Idoso , Anticoncepcionais/administração & dosagem , Tubas Uterinas/imunologia , Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/prevenção & controle , Ovário/patologia , Ovulação/efeitos dos fármacos , Modelos de Riscos Proporcionais , Estudos Prospectivos , História Reprodutiva , Medição de Risco , Fatores de Risco
9.
Int J Cancer ; 146(3): 664-670, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30895617

RESUMO

Breast cancer is the most common cancer and the second-leading cause of cancer-related death among women. Inconsistent findings for the relationship between melatonin levels, sleep duration and breast cancer have been reported. We investigated the association of sleep duration at cohort entry and its interaction with body mass index (BMI) with risk of developing breast cancer in the large population-based Multiethnic Cohort study. Among the 74,481 at-risk participants, 5,790 breast cancer cases were identified during the study period. Although we detected no significant association between sleep duration and breast cancer incidence, higher risk estimates for short (HR = 1.03; 95% CI: 0.97-1.09) and long sleep (HR = 1.05; 95% CI: 0.95-1.15) compared to normal sleep (7-8 hr) were found. The patterns for models stratified by age, BMI, ethnicity and hormone receptor status were similar but did not indicate significant interaction effects. When examining the combined sleep duration and BMI interaction effect, in comparison to the normal BMI-normal sleep group, risk estimates for underweight, overweight and obesity were similar across categories of sleep duration (≤6, 7-8, and ≥9 hr). The underweight-normal sleep group had lower breast cancer incidence (HR = 0.66, 95% CI: 0.50-0.86), whereas the overweight-short sleep, overweight-normal sleep group and all obese women experienced elevated breast cancer incidence. The respective HRs for short, normal and long sleep among obese women were 1.35 (95% CI: 1.20-1.53), 1.27 (95% CI: 1.15-1.42) and 1.46 (95% CI: 1.21-1.76). Future perspectives need to examine the possibility that sleep quality, variations in circadian rhythm and melatonin are involved in breast cancer etiology.


Assuntos
Neoplasias da Mama/epidemiologia , Sobrepeso/epidemiologia , Sono/fisiologia , Magreza/epidemiologia , Idoso , Índice de Massa Corporal , Neoplasias da Mama/etiologia , California/epidemiologia , Ritmo Circadiano/fisiologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Sobrepeso/complicações , Medição de Risco , Fatores de Risco , Magreza/complicações , Fatores de Tempo
10.
Nature ; 570(7762): 514-518, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31217584

RESUMO

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions13-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudo de Associação Genômica Ampla/métodos , Hispano-Americanos/genética , Grupos Minoritários , Herança Multifatorial/genética , Saúde da Mulher , Estatura/genética , Estudos de Coortes , Feminino , Genética Médica/métodos , Equidade em Saúde/tendências , Disparidades nos Níveis de Saúde , Humanos , Masculino , Estados Unidos
12.
Breast Cancer Res Treat ; 173(3): 637-645, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30367331

RESUMO

PURPOSE: The purpose of the study was to investigate the association of type 2 diabetes (T2D) with survival of breast cancer (BC) patients across five ethnic groups within the Multiethnic Cohort study. METHODS: Between recruitment in 1993-1996 and 2013, 7570 incident BC cases were identified through SEER cancer registries in Hawaii and California. T2D diagnosed before BC was ascertained in 1013 women from self-reports and confirmed by administrative data sources. Covariate information was collected by questionnaire. Cox regression analysis with age as the time metric and BMI as time-varying exposure was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BC-specific and all-cause survival while adjusting for known prognostic factors. RESULTS: In total, 2119 all-cause and 730 BC-specific deaths were recorded with corresponding 5-year survival rates of 86 and 93%. T2D was not a significant predictor of BC-specific survival (HR 0.84; 95% CI 0.65-1.09), but mortality was 36% lower for those with < 7 years of T2D than a longer history of T2D. On the other hand, all-cause mortality was higher in women with T2D (HR 1.23; 95% CI 1.08-1.40), especially in women with T2D of ≥ 7 years duration (HR 1.27; 95% CI 1.07-1.49). In women receiving none or either chemotherapy or radiation but not both, T2D predicted higher all-cause mortality (Pinteraction = 0.004). Variations in the association of T2D with mortality across ethnic groups were small. CONCLUSIONS: T2D was associated with higher all-cause but not BC-specific mortality among women with BC in the Multiethnic Cohort study. However, T2D affected survival in cases who did not receive both radiation and chemotherapy.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Diabetes Mellitus Tipo 2/complicações , Idoso , Neoplasias da Mama/epidemiologia , California/epidemiologia , Causas de Morte , Estudos de Coortes , Comorbidade , Diabetes Mellitus Tipo 2/epidemiologia , Grupos Étnicos , Feminino , Hawaii/epidemiologia , Humanos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Programa de SEER , Inquéritos e Questionários , Taxa de Sobrevida
13.
Eur J Clin Nutr ; 73(5): 671-678, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29795238

RESUMO

BACKGROUND/OBJECTIVES: As cocoa products may be protective against chronic disease due to their polyphenol content, the current study determined the association of chocolate consumption and flavanol intake with type-2 diabetes (T2D) incidence in the Multiethnic Cohort (MEC) Study. SUBJECTS/METHODS: The analysis included 151,691 participants of Native Hawaiian, Japanese American, Latino, African American, and white ancestry with 8487 incident T2D cases after 7.8 ± 3.5 years of follow-up. T2D status was based on three self-reports and confirmed by at least one of three administrative data sources. Dietary intake was assessed using a validated quantitative food frequency questionnaire, and flavanols from cocoa products were estimated from self-reported consumption of chocolate candy and drinks. Cox hazard regression, adjusted for potential confounders was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: For chocolate candy, both the highest vs. lowest (≥10 vs. <1 g/day) consumption (HR = 0.90; 95% CI, 0.83-0.97; ptrend = 0.01) and the frequency (≥4/week vs. <1/month) of intake (HR = 0.81; 95% CI, 0.72-0.91; ptrend = 0.0002) were inversely associated with T2D. The estimated flavanol intake from cocoa products (≥3 vs. <1 mg/day) also showed an inverse association with T2D risk (HR = 0.93; 95% CI, 0.88-0.99; ptrend = 0.02). Significant interaction terms indicated that the inverse relation was limited to Japanese Americans, normal-weight individuals, and to those without comorbidities. CONCLUSIONS: The current study confirms previous reports that participants with high intake of chocolate products and cocoa-derived flavanols experience a reduced risk of developing T2D even after controlling for sugar intake, diet quality, and other aspects of the diet.


Assuntos
Cacau , Chocolate , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/etnologia , Grupos Étnicos , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia
14.
Front Cardiovasc Med ; 5: 19, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29740590

RESUMO

Background: Coronary heart disease (CHD) is the most common cause of death worldwide. Previous studies have identified numerous common CHD susceptibility loci, with the vast majority identified in populations of European ancestry. How well these findings transfer to other racial/ethnic populations remains unclear. Methods and Results: We examined the generalizability of the associations with 71 known CHD loci in African American, Latino and Japanese men and women in the Multiethnic Cohort (6,035 cases and 11,251 controls). In the combined multiethnic sample, 78% of the loci demonstrated odds ratios that were directionally consistent with those previously reported (p = 2 × 10-6), with this fraction ranging from 59% in Japanese to 70% in Latinos. The number of nominally significant associations across all susceptibility regions ranged from only 1 in Japanese to 11 in African Americans with the most statistically significant association observed through locus fine-mapping noted for rs3832016 (OR = 1.16, p = 2.5×10-5) in the SORT1 region on chromosome 1p13. Lastly, we examined the cumulative predictive effect of CHD SNPs across populations with improved power by creating genetic risk scores (GRSs) that summarize an individual's aggregated exposure to risk variants. We found the GRSs to be significantly associated with risk in African Americans (OR = 1.03 per allele; p = 4.1×10-5) and Latinos (OR = 1.03; p = 2.2 × 10-8), but not in Japanese (OR = 1.01; p = 0.11). Conclusions: While a sizable fraction of the known CHD loci appear to generalize in these populations, larger fine-mapping studies will be needed to localize the functional alleles and better define their contribution to CHD risk in these populations.

15.
J Natl Cancer Inst ; 110(12): 1342-1351, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29741696

RESUMO

Background: Endometrial cancer is the second most common cancer among female cancer survivors in the United States. Cardiovascular disease is the leading cause of death among endometrial cancer survivors. Studies that examine long-term cardiovascular outcomes among endometrial cancer survivors are critical. Methods: Cohorts of 2648 endometrial cancer survivors diagnosed between 1997 and 2012 and 10 503 age-matched women from the general population were identified. Cardiovascular disease diagnoses were identified from electronic medical records and statewide ambulatory surgery and statewide inpatient data. Cox regression models were used to estimate hazard ratios (HRs) at one to five years, more than five to 10 years, and more than 10 years after cancer diagnosis. Results: Between one and five years after diagnosis, increased cardiovascular risks among endometrial cancer survivors were observed for phlebitis, thrombophlebitis, and thromboembolism (HR = 2.07, 99% confidence interval [CI] = 1.57 to 2.72), pulmonary heart disease (HR = 1.74, 99% CI = 1.26 to 2.40), and atrial fibrillation (HR = 1.50, 99% CI = 1.07 to 2.11). At more than five to 10 years, some elevated risk persisted for cardiovascular diseases. Compared with patients who had surgery, patients who additionally had radiation therapy and/or chemotherapy were at increased risk for heart and circulatory system disorders between one and five years after cancer diagnosis. Older age and obesity were also risk factors for hypertension and heart disease among endometrial cancer survivors. Conclusions: Endometrial cancer survivors are at higher risk for various adverse long-term cardiovascular outcomes compared with women from the general population. This study suggests that increased monitoring for cardiovascular diseases may be necessary for endometrial cancer patients for 10 years after cancer diagnosis.


Assuntos
Sobreviventes de Câncer , Doenças Cardiovasculares/epidemiologia , Neoplasias do Endométrio/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Vigilância da População , Modelos de Riscos Proporcionais , Programa de SEER
16.
Int J Cancer ; 143(2): 263-268, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29441528

RESUMO

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre-existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all-cause and 678 CRC-specific deaths after a mean follow-up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC-specific and all-cause survival while adjusting for known confounders. Overall, CRC-specific survival was not associated with pre-existing T2D (HR = 0.84; 95% CI = 0.67-1.07). However, a significant interaction was seen for comorbidity (pinteraction  = 0.03) with better survival among those without pre-existing conditions (HR = 0.49; 95% CI = 0.25-0.96) while no association was seen in patients with comorbid conditions. All-cause mortality was also not related to pre-existing T2D (HR = 1.11; 95% CI = 0.98-1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19-1.56). Stratification by T2D duration suggested higher CRC-specific and all-cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre-existing T2D had no influence on disease-specific and all-cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.


Assuntos
Neoplasias Colorretais/etnologia , Neoplasias Colorretais/mortalidade , Diabetes Mellitus Tipo 2/etnologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Comorbidade , Feminino , Hawaii/etnologia , Humanos , Los Angeles/etnologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida
17.
Sleep Health ; 4(1): 27-32, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29332675

RESUMO

OBJECTIVES: As an emerging risk factor for the rising incidence of type 2 diabetes, we examined sleep duration in relation to type 2 diabetes and several biomarkers. DESIGN: Prospective cohort recruited 1993-1996. SETTING: The Multiethnic Cohort in Hawaii and California. PARTICIPANTS: A cohort of 151,691 White, African American, Japanese American, Native Hawaiian, and Latino participants; 9695 cohort members had biomarker measurements. MEASUREMENTS: Sleep duration was self-reported at cohort entry. Diabetes status was obtained from 3 questionnaires and confirmed by 3 administrative data sources. Biomarkers were measured by standard assays 9.6±2.1 years after cohort entry. We estimated diabetes risk as a time-varying outcome using Cox regression adjusted for body mass index assessed at 3 time points and other known confounders and computed adjusted means of biomarkers by sleep hours. RESULTS: During 7.9±3.5 years of follow-up, 8487 new diabetes cases were diagnosed. Long sleep duration (≥9 hours), as compared with 7-8 hours, was significantly associated with higher incidence (hazard ratio, 1.12; 95% confidence interval 1.04-1.21), but the 4% elevated incidence for short sleep duration (≤6 hours) did not reach significance (95% confidence interval 0.99-1.09). After stratification, the associations appeared stronger in Japanese American than other ethnic groups and in participants without comorbidity. Hours of sleep were positively associated with C-reactive protein and triglycerides and inversely related to high-density lipoprotein cholesterol and adiponectin but not with leptin levels and homeostatic model assessment of insulin resistance. CONCLUSION: In this multiethnic population, the 12% higher diabetes risk for long sleep hours may be mediated through inflammation, a poor lipid profile, and lower adiponectin levels.


Assuntos
Afro-Americanos/estatística & dados numéricos , Americanos Asiáticos/estatística & dados numéricos , Diabetes Mellitus Tipo 2/etnologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Hispano-Americanos/estatística & dados numéricos , Sono , Idoso , Biomarcadores/sangue , California/epidemiologia , Feminino , Hawaii/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Autorrelato , Fatores de Tempo
18.
Cancer Epidemiol Biomarkers Prev ; 26(6): 854-861, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28087607

RESUMO

Background: Obesity has been more consistently associated with breast cancer than type II diabetes. This analysis examined the combination of the two factors in the Multiethnic Cohort (MEC).Methods: Women ages 45-75 years entered the MEC in 1993-1996 by completing a questionnaire. Type II diabetes status was self-reported at baseline, two follow-up questionnaires, and confirmed by administrative data. Cancers were identified from tumor registries and deaths through vital records until 2010. Cox regression was applied to estimate HRs and 95% confidence intervals (CI) for BMI and type II diabetes status alone and in combination.Results: Among 103,721 (25,146 white, 20,255 African American, 7,681 Native Hawaiian, 28,012 Japanese American, 22,627 Latina) women with 14,558 type II diabetes cases, 6,692 women developed breast cancer during 14.8 ± 4.1 years of follow-up. Type II diabetes was significantly associated with breast cancer risk (HR, 1.15; 95% CI, 1.07-1.23), but including body mass index (BMI) lowered the HR to 1.08 (95% CI, 1.00-1.16). Ethnic-specific BMI-adjusted models showed elevated risks for type II diabetes in Latinas only (HR, 1.30; 95% CI, 1.11-1.52). In contrast, obesity predicted statistically significant 21%-46% higher risks, after type II diabetes adjustment, in all ethnic groups except Latinas (HR, 1.17; 95% CI, 0.99-1.38).Conclusions: As reported previously, inclusion of BMI weakened the association of type II diabetes with breast cancer. Type II diabetes status, but not BMI, was primarily associated with higher breast cancer risk in Latinas.Impact: The role of obesity and type II diabetes in breast cancer etiology may differ by ethnicity suggesting metabolic differences related to obesity. Cancer Epidemiol Biomarkers Prev; 26(6); 854-61. ©2017 AACR.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/etiologia , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Idoso , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
19.
PLoS One ; 10(11): e0143256, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26606540

RESUMO

Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10-5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.


Assuntos
Índice de Massa Corporal , Neoplasias do Endométrio/etiologia , Predisposição Genética para Doença , Obesidade/complicações , Obesidade/genética , Idoso , Estudos de Casos e Controles , Neoplasias do Endométrio/epidemiologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco
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