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1.
Urol Oncol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33423934

RESUMO

BACKGROUND: Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs). METHODS: Within the Surveillance Epidemiology and End Results database (2005-2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality. RESULTS: Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40-0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15-1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46-0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27-0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12-6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48-16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively. CONCLUSIONS: This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33355191

RESUMO

BACKGROUND: Limited studies have investigated racial/ethnic survival disparities for breast cancer (BC) defined by estrogen receptor (ER) and progesterone receptor (PR) status in a multiethnic population. METHODS: Using multivariable Cox proportional hazards models, we assessed associations of race/ethnicity with ER/PR-specific BC mortality in 10,366 Californian women diagnosed with BC from 1993-2009. We evaluated joint associations of race/ethnicity, healthcare, sociodemographic, and lifestyle factors with mortality. RESULTS: Among women with ER/PR+ BC, BC-specific mortality was similar among Hispanic and Asian American women, but higher among African American women (hazard ratio (HR) 1.31, 95% confidence interval 1.05-1.63) compared to non-Hispanic White (NHW) women. BC-specific mortality was modified by surgery type, hospital type, education, neighborhood socioeconomic status (SES), smoking history, and alcohol consumption. Among African American women, BC-specific mortality was higher among those treated at non-accredited hospitals (HR 1.57, CI 1.21-2.04) and those from lower SES neighborhoods (HR 1.48, CI 1.16-1.88) compared to NHW women without these characteristics. BC-specific mortality was higher among African American women with at least some college education (HR 1.42, CI 1.11-1.82) compared to NHW women with similar education. For ER-/PR- disease, BC-specific mortality did not differ by race/ethnicity and associations of race/ethnicity with BC-specific mortality varied only by neighborhood SES among African American women. CONCLUSIONS: Racial/ethnic survival disparities are more striking for ER/PR+ than ER-PR- BC. Social determinants and lifestyle factors may explain some of the survival disparities for ER/PR+ BC. IMPACT: Addressing these factors may help reduce the higher mortality of African American women with ER/PR+ BC.

4.
J Natl Cancer Inst ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010161

RESUMO

BACKGROUND: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. METHODS: Among prostate cancer cases diagnosed in 2007 in the U.S. SEER-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). RESULTS: In our case population (n = 55,900), 3,073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM stage and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of stage T4 or N1 or M1 or Gleason score ≥8 prostate cancer, as this definition had one of the higher PPVs (0.23, 95% confidence interval [CI] 0.22-0.24) and reasonable sensitivity (0.66, 95% CI 0.64-0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. CONCLUSIONS: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced stage (T4 or N1 or M1), high grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

5.
Hepatol Commun ; 4(8): 1112-1123, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32766472

RESUMO

The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10-15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10-8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = -0.046; P = 0.04), and sex hormone binding globulin (beta = -0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

6.
Hum Mol Genet ; 29(13): 2275-2284, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32491157

RESUMO

Statistical imputation applied to genome-wide array data is the most cost-effective approach to complete the catalog of genetic variation in a study population. However, imputed genotypes in underrepresented populations incur greater inaccuracies due to ascertainment bias and a lack of representation among reference individuals, further contributing to the obstacles to study these populations. Here we examined the consequences due to the lack of representation by genotyping in a large number of self-reported Native Hawaiians (N = 3693) a functionally important, Polynesian-specific variant in the CREBRF gene, rs373863828. We found the derived allele was significantly associated with several adiposity traits with large effects (e.g. ~ 1.28 kg/m2 per allele in body mass index as the most significant; P = 7.5 × 10-5), consistent with the original findings in Samoans. Due to the current absence of Polynesian representation in publicly accessible reference sequences, rs373863828 or its proxies could not be tested through imputation using these existing resources. Moreover, the association signals at the entire CREBRF locus could not be captured by alternative approaches, such as admixture mapping. In contrast, highly accurate imputation can be achieved even if a small number (<200) of internally constructed Polynesian reference individuals were available; this would increase sample size and improve the statistical evidence of associations. Taken together, our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci such as CREBRF. Yet, they could be easily detected and prioritized with improved representation of diverse populations in sequencing studies.

7.
JCO Oncol Pract ; 16(6): e517-e528, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32521220

RESUMO

INTRODUCTION: Racial/ethnic disparities in breast cancer survival are well documented, but the influence of health care institutions is unclear. We therefore examined the effect of hospital characteristics on survival. METHODS: Harmonized data pooled from 5 case-control and prospective cohort studies within the California Breast Cancer Survivorship Consortium were linked to the California Cancer Registry and the California Neighborhoods Data System. The study included 9,701 patients with breast cancer who were diagnosed between 1993 and 2007. First reporting hospitals were classified by hospital type-National Cancer Institute (NCI) -designated cancer center, American College of Surgeons (ACS) Cancer Program, other-and hospital composition of the neighborhood socioeconomic status and race/ethnicity of patients with cancer. Multivariable Cox proportional hazards models adjusted for clinical and patient-level prognostic factors were used to examine the influence of hospital characteristics on survival. RESULTS: Fewer than one half of women received their initial care at an NCI-designated cancer center (5%) or ACS program (38%) hospital. Receipt of initial care in ACS program hospitals varied by race/ethnicity-highest among non-Latina White patients (45%), and lowest among African Americans (21%). African-American women had superior breast cancer survival when receiving initial care in ACS hospitals versus other hospitals (non-ACS program and non-NCI-designated cancer center; hazard ratio, 0.67; 95% CI, 0.55 to 0.83). Other hospital characteristics were not associated with survival. CONCLUSION: African American women may benefit significantly from breast cancer care in ACS program hospitals; however, most did not receive initial care at such facilities. Future research should identify the aspects of ACS program hospitals that are associated with higher survival and evaluate strategies by which to enhance access to and use of high-quality hospitals, particularly among African American women.

8.
Cancer Causes Control ; 31(8): 713-721, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32440828

RESUMO

PURPOSE: Hispanic men in the USA experience the second-highest incidence rate of testicular germ cell tumors (TGCTs), behind non-Hispanic (NH) White men, and have experienced steep increases in TGCT in recent decades. It is unknown whether increases in incidence differ according to neighborhood sociodemographic factors. METHODS: We conducted a population-based study of n = 3759 Hispanic and n = 8469 NH White men (n = 12,228 total) diagnosed with TGCT in California during the three most recent pericensal periods. We calculated incidence rates according to neighborhood socioeconomic status (nSES) and among Hispanics, according to ethnic enclave. We calculated incidence rate ratios to compare rates across nSES and ethnic enclave and to examine changes in rates over pericensal time periods according to these neighborhood factors for major histologic types (i.e., seminoma and nonseminoma). RESULTS: Hispanic men residing in high SES, compared to low SES, neighborhoods had greater incidence of seminoma and nonseminoma testicular cancer across pericensal periods, as did Hispanic men in low enclave (less ethnic), compared to high enclave, neighborhoods. Between the periods 1998-2002 and 2008-2012, Hispanic men residing in low SES neighborhoods experienced a 39% increased incidence of seminoma, while those residing in low and middle SES neighborhoods experienced 87% and 48% increased incidence of nonseminoma, respectively. CONCLUSION: While TGCT incidence has increased among all Hispanic men, incidence increases appear to be driven disproportionately by those residing in lower SES and lower enclave neighborhoods, particularly for nonseminoma.


Assuntos
Hispano-Americanos , Neoplasias Embrionárias de Células Germinativas/etnologia , Seminoma/etnologia , Neoplasias Testiculares/etnologia , Adolescente , Adulto , California/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Características de Residência , Seminoma/epidemiologia , Classe Social , Neoplasias Testiculares/epidemiologia , Adulto Jovem
9.
Cancer ; 126(13): 3013-3020, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32307706

RESUMO

BACKGROUND: Initiating screening at an earlier age based on cancer family history is one of the primary recommended strategies for the prevention and detection of early-onset colorectal cancer (EOCRC), but data supporting the effectiveness of this approach are limited. The authors assessed the performance of family history-based guidelines for identifying individuals with EOCRC. METHODS: The authors conducted a population-based, case-control study of individuals aged 40 to 49 years with (2473 individuals) and without (772 individuals) incident CRC in the Colon Cancer Family Registry from 1998 through 2007. They estimated the sensitivity and specificity of family history-based criteria jointly recommended by the American Cancer Society, the US Multi-Society Task Force on CRC, and the American College of Radiology in 2008 for early screening, and the age at which each participant could have been recommended screening initiation if these criteria had been applied. RESULTS: Family history-based early screening criteria were met by approximately 25% of cases (614 of 2473 cases) and 10% of controls (74 of 772 controls), with a sensitivity of 25% and a specificity of 90% for identifying EOCRC cases aged 40 to 49 years. Among 614 individuals meeting early screening criteria, 98.4% could have been recommended screening initiation at an age younger than the observed age of diagnosis. CONCLUSIONS: Of CRC cases aged 40 to 49 years, 1 in 4 met family history-based early screening criteria, and nearly all cases who met these criteria could have had CRC diagnosed earlier (or possibly even prevented) if earlier screening had been implemented as per family history-based guidelines. Additional strategies are needed to improve the detection and prevention of EOCRC for individuals not meeting family history criteria for early screening.

10.
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.

11.
Cancer Epidemiol Biomarkers Prev ; 29(5): 966-973, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32132150

RESUMO

BACKGROUND: Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies. METHODS: We developed a VAT prediction score by regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case-control studies of postmenopausal breast (950 case-control pairs) and colorectal (831 case-control pairs) cancer in an independent sample in MEC. Abdominal MRI-derived VAT; circulating biomarkers of metabolic, hormonal, and inflammation dysfunctions; and ORs for incident cancer adjusted for BMI and other risk factors were assessed. RESULTS: The final score, composed of nine biomarkers, BMI, and height, explained 11% and 15% more of the variance in VAT than BMI alone in men and women, respectively. The area under the receiver operator curve for VAT >150 cm2 was 0.90 in men and 0.86 in women. The VAT score was associated with risk of breast cancer [OR (95% confidence interval [CI]) by increasing tertiles: 1.00, 1.09 (0.86-1.39), 1.48 (1.16-1.89); P trend = 0.002] but not with colorectal cancer (P = 0.84), although an association [1.00, 0.98 (0.68-1.39), 1.24 (0.88-1.76); P trend = 0.08] was suggested for this cancer after excluding cases that occurred within 7 years of blood draw (P heterogeneity = 0.06). CONCLUSIONS: The VAT score predicted risks of postmenopausal breast cancer and can be used for risk assessment in diverse populations. IMPACT: These findings provide specific evidence for a role of VAT in breast cancer.

12.
Am J Clin Nutr ; 111(6): 1226-1234, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32055828

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well understood and few human studies have investigated microbes involved in its production. OBJECTIVES: Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO. METHODS: We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60-77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1-V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution. RESULTS: Median (IQR) concentration of plasma TMAO was 3.05 µmol/L (2.10-4.60 µmol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate < 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter smithii. CONCLUSIONS: Plasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways.


Assuntos
Betaína/sangue , Doenças Cardiovasculares/sangue , Carnitina/sangue , Colina/sangue , Microbioma Gastrointestinal , Metilaminas/sangue , Adiposidade , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biomarcadores/sangue , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/microbiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Metilaminas/metabolismo , Pessoa de Meia-Idade
13.
Nat Commun ; 11(1): 27, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911640

RESUMO

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10-8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10-12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21-1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01-1.35) and lung cancer in never smokers (OR = 1.56, 1.05-2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.


Assuntos
Neoplasias Pulmonares/genética , Pulmão/fisiopatologia , Adulto , Idoso , Feminino , Volume Expiratório Forçado , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Testes de Função Respiratória , Capacidade Vital
14.
SSM Popul Health ; 10: 100532, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31909167

RESUMO

Background: Neighborhood environment has been associated with health behaviors. Despite the evidence of the influence of neighborhood social and physical factors on cancer risk, no research has evaluated whether changes in the neighborhood obesogenic environment, either by physical moves to different neighborhoods or experiencing neighborhood redevelopment or neglect, affect cancer risk. Methods: The association of change in neighborhood environment attributes (socioeconomic status, population density, restaurant and retail food environments, numbers of recreational facilities and businesses, commute patterns, traffic density, and street connectivity) with colorectal cancer (CRC) risk was examined among 95,472 Los Angeles, CA, Multiethnic Cohort participants, including 2295 invasive CRC cases diagnosed between 1993 and 2010 using Cox proportional hazards regression, adjusting for age, race/ethnicity, other risk factors including BMI and physical activity, and baseline levels of neighborhood attributes. Stratified analyses were conducted by racial/ethnic group and moving status. Results: 40% of participants moved (changed physical residence) during follow-up. Across all races/ethnicities, upward change in population density was statistically significantly associated with higher CRC risk among male and female non-movers (HR: 1.35 and 1.41, respectively). The same association was also observed separately among female African American and Japanese American non-movers, male Latino non-movers, female African American and male White movers. Downward change in population density was significantly related to higher CRC risk among female non-movers (HR: 1.33). Downward change in traffic density was associated with lower CRC risk among male non-movers but with higher CRC risk among female movers (HR: 0.66 and 1.43, respectively). Downward changes in street connectivity or the number of recreational facilities were associated with higher CRC risk (HR: 1.34 and 1.54, respectively). Upward change in the number of recreational facilities was associated with lower CRC risk among female non-movers (HR: 0.70). Changes in the other neighborhood attributes did not exhibit significant associations with CRC risk within more than one racial/ethnic group. Conclusion: Changes over time in neighborhood attributes have an effect on the risk of colorectal cancer, which is separate from the baseline levels of the same attributes and individual-level risk factors, and differs between sexes, movers and non-movers and across racial/ethnic groups.

15.
Int J Cancer ; 146(3): 699-711, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30924138

RESUMO

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NOx , NO2 , PM10 , PM2.5 ), land use regression (LUR, NOx , NO2 ) and California Line Source Dispersion model (CALINE4, NOx , PM2.5 ) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993-1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NOx (per 50 parts per billion [ppb]) and NO2 (per 20 ppb) determined by kriging and LUR and with PM2.5 and PM10 (per 10 µg/m3 ) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NOx (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02-1.79), NO2 (HR = 1.44, 95% CI: 1.04-1.99), PM10 (HR = 1.29, 95% CI: 1.07-1.55) and PM2.5 (HR = 1.85, 95% CI: 1.15-2.99) determined by kriging and NOx (HR = 1.21, 95% CI:1.01-1.45) and NO2 (HR = 1.26, 95% CI: 1.00-1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NOx and NO2 among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Neoplasias da Mama/epidemiologia , Material Particulado/efeitos adversos , Afro-Americanos/estatística & dados numéricos , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Americanos Asiáticos/estatística & dados numéricos , Neoplasias da Mama/etiologia , California/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Material Particulado/análise , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
16.
PLoS One ; 14(10): e0222284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31577800

RESUMO

BACKGROUND: The mitochondrial genome encodes for thirty-seven proteins, among them thirteen are essential for the oxidative phosphorylation (OXPHOS) system. Inherited variation in mitochondrial genes may influence cancer development through changes in mitochondrial proteins, altering the OXPHOS process and promoting the production of reactive oxidative species. METHODS: To investigate the association between mitochondrial genetic variation and breast cancer risk, we tested 314 mitochondrial SNPs (mtSNPs), capturing four complexes of the mitochondrial OXPHOS pathway and mtSNP groupings for rRNA and tRNA, in 2,723 breast cancer cases and 3,260 controls from the Multiethnic Cohort Study. RESULTS: We examined the collective set of 314 mtSNPs as well as subsets of mtSNPs grouped by mitochondrial OXPHOS pathway, complexes, and genes, using the sequence kernel association test and adjusting for age, sex, and principal components of global ancestry. We also tested haplogroup associations using unconditional logistic regression and adjusting for the same covariates. Stratified analyses were conducted by self-reported maternal race/ethnicity. No significant mitochondrial OXPHOS pathway, gene, and haplogroup associations were observed in African Americans, Asian Americans, Latinos, and Native Hawaiians. In European Americans, a global test of all genetic variants of the mitochondrial genome identified an association with breast cancer risk (P = 0.017, q = 0.102). In mtSNP-subset analysis, the gene MT-CO2 (P = 0.001, q = 0.09) in Complex IV (cytochrome c oxidase) and MT-ND2 (P = 0.004, q = 0.19) in Complex I (NADH dehydrogenase (ubiquinone)) were significantly associated with breast cancer risk. CONCLUSIONS: In summary, our findings suggest that collective mitochondrial genetic variation and particularly in the MT-CO2 and MT-ND2 may play a role in breast cancer risk among European Americans. Further replication is warranted in larger populations and future studies should evaluate the contribution of mitochondrial proteins encoded by both the nuclear and mitochondrial genomes to breast cancer risk.


Assuntos
Neoplasias da Mama/genética , Grupos Étnicos/genética , Predisposição Genética para Doença , Variação Genética , Mitocôndrias/genética , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genoma Mitocondrial , Haplótipos/genética , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Adulto Jovem
17.
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
18.
Annu Rev Genomics Hum Genet ; 20: 181-200, 2019 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-30978304

RESUMO

The past decade has seen a technological revolution in human genetics that has empowered population-level investigations into genetic associations with phenotypes. Although these discoveries rely on genetic variation across individuals, association studies have overwhelmingly been performed in populations of European descent. In this review, we describe limitations faced by single-population studies and provide an overview of strategies to improve global representation in existing data sets and future human genomics research via diversity-focused, multiethnic studies. We highlight the successes of individual studies and meta-analysis consortia that have provided unique knowledge. Additionally, we outline the approach taken by the Population Architecture Using Genomics and Epidemiology (PAGE) study to develop best practices for performing genetic epidemiology in multiethnic contexts. Finally, we discuss how limiting investigations to single populations impairs findings in the clinical domain for both rare-variant identification and genetic risk prediction.


Assuntos
Grupos de Populações Continentais/genética , Grupos Étnicos/genética , Variação Genética , Genética Humana/tendências , Metagenômica/tendências , Epidemiologia Molecular/tendências , Viés , Bases de Dados Factuais , Genoma Humano , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fenótipo
19.
Neuro Oncol ; 21(4): 498-507, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30615143

RESUMO

BACKGROUND: Meningioma is the most common intracranial tumor in the US and its etiology remains poorly understood. Meningioma has been predominantly studied among white populations. The aim of this study was to evaluate the associations of anthropometric, comorbidity, and hormonal factors with meningioma in an ethnically diverse population. METHODS: A nested case-control analysis was performed within the Multiethnic Cohort (MEC). Meningioma cases were identified via linkage with Medicare and the California Office of Statewide Health Planning and Development Hospital Discharge data and were matched to up to 10 controls. Anthropometric, comorbidities, physical activity level, and hormonal factors at baseline based on questionnaires were evaluated for association with meningioma. RESULTS: A total of 894 cases and 8918 matched controls were included in this study. Increasing body mass index (BMI) (P-trend = 0.041) and weight increases since age 21 (P-trend = 0.0052) were positively associated with meningioma. Hormonal factors including oral contraceptive use (odds ratio [OR]: 1.24; 95% CI: 1.01-1.51) and estrogen hormonal therapy use (per 5 years, OR: 1.07; 95% CI: 1.01-1.15) were associated with meningioma risk. Hypertension was positively associated with meningioma (OR: 1.26; 95% CI: 1.09-1.47), with individuals who reported a history of both hypertension and diabetes showing a stronger association (OR: 1.54; 95% CI: 1.17-2.03). The tests for heterogeneity across race/ethnicity were not statistically significant (P heterogeneity ≥ 0.17); however, the association of BMI with meningioma was mainly observed in Japanese Americans (P-trend = 0.0036) and hypertension in Japanese Americans (OR: 1.63; 95% CI: 1.17-2.27) and Native Hawaiians (OR: 1.86; 95% CI: 1.02-3.40). CONCLUSION: Obesity, hormonal factors, and hypertension were associated with meningioma in an ethnically diverse population.


Assuntos
Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Anticoncepcionais Orais Hormonais/efeitos adversos , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Neoplasias Meníngeas/etiologia , Meningioma/etiologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco
20.
Cancer Epidemiol Biomarkers Prev ; 28(1): 154-162, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30206059

RESUMO

BACKGROUND: Measurement reliability and biological stability need to be considered when developing sampling protocols for population-based fecal microbiome studies. METHODS: Stool samples were collected biannually over a 2-year period and sequenced for the V1-V3 region of the 16S rRNA gene in 50 participants from the Multiethnic Cohort Study. We evaluated the temporal stability of the fecal microbiome on a community level with permutational multivariate analysis of variance (PERMANOVA), as well as on taxa and diversity measures with intraclass correlation coefficients. RESULTS: Interindividual differences were the predominant source of fecal microbiome variation, and variation within individual was driven more by changing abundances than by the complete loss or introduction of taxa. Phyla and diversity measures were reliable over the 2 years. Most genera were stable over time, although those with low abundances tended to be more dynamic. Reliability was lower among participants who used antibiotics, with the greatest difference seen in samples taken within 1 month of reported use. CONCLUSIONS: The fecal microbiome as a whole is stable over a 2-year period, although certain taxa may exhibit more temporal variability. IMPACT: When designing large epidemiologic studies, a single sample is sufficient to capture the majority of the variation in the fecal microbiome from 16S rRNA gene sequencing, while multiple samples may be needed for rare or less-abundant taxa.


Assuntos
Bactérias/isolamento & purificação , Variação Biológica da População , Fezes/microbiologia , Microbioma Gastrointestinal , Fatores de Tempo , Idoso , Estudos de Coortes , Grupos de Populações Continentais , Código de Barras de DNA Taxonômico , DNA Bacteriano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S , Reprodutibilidade dos Testes
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