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1.
Int J Cancer ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544892

RESUMO

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.

2.
JAMA Oncol ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33630024

RESUMO

Importance: Women with pathogenic variants in BRCA1 and BRCA2 are at high risk of developing breast and ovarian cancers. They usually undergo intensive cancer surveillance and may also consider surgical interventions, such as risk-reducing mastectomy or risk-reducing salpingo-oophorectomy (RRSO). Risk-reducing salpingo-oophorectomy has been shown to reduce ovarian cancer risk, but its association with breast cancer risk is less clear. Objective: To assess the association of RRSO with the risk of breast cancer in women with BRCA1 and BRCA2 pathogenic variants. Design, Setting, and Participants: This case series included families enrolled in the Breast Cancer Family Registry between 1996 and 2000 that carried an inherited pathogenic variant in BRCA1 (498 families) or BRCA2 (378 families). A survival analysis approach was used that was designed specifically to assess the time-varying association of RRSO with breast cancer risk and accounting for other potential biases. Data were analyzed from August 2019 to November 2020. Exposure: Risk-reducing salpingo-oophorectomy. Main Outcomes and Measures: In all analyses, the primary end point was the time to a first primary breast cancer. Results: A total of 876 families were evaluated, including 498 with BRCA1 (2650 individuals; mean [SD] event age, 55.8 [19.1] years; 437 White probands [87.8%]) and 378 with BRCA2 (1925 individuals; mean [SD] event age, 57.0 [18.6] years; 299 White probands [79.1%]). Risk-reducing salpingo-oophorectomy was associated with a reduced risk of breast cancer for BRCA1 and BRCA2 pathogenic variant carriers within 5 years after surgery (hazard ratios [HRs], 0.28 [95% CI, 0.10-0.63] and 0.19 [95% CI, 0.06-0.71], respectively), whereas the corresponding HRs were weaker after 5 years postsurgery (HRs, 0.64 [95% CI, 0.38-0.97] and 0.99 [95% CI; 0.84-1.00], respectively). For BRCA1 and BRCA2 pathogenic variant carriers who underwent RRSO at age 40 years, the cause-specific cumulative risk of breast cancer was 49.7% (95% CI, 40.0-60.3) and 52.7% (95% CI, 47.9-58.7) by age 70 years, respectively, compared with 61.0% (95% CI, 56.7-66.0) and 54.0% (95% CI, 49.3-60.1), respectively, for women without RRSO. Conclusions and Relevance: Although the primary indication for RRSO is the prevention of ovarian cancer, it is also critical to assess its association with breast cancer risk in order to guide clinical decision-making about RRSO use and timing. The results of this case series suggest a reduced risk of breast cancer associated with RRSO in the immediate 5 years after surgery in women carrying BRCA1 and BRCA2 pathogenic variants, and a longer-term association with cumulative breast cancer risk in women carrying BRCA1 pathogenic variants.

3.
N Engl J Med ; 384(5): 440-451, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33471974

RESUMO

BACKGROUND: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Variação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Razão de Chances , Risco , Análise de Sequência de DNA , Adulto Jovem
4.
PLoS One ; 16(1): e0244819, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444363

RESUMO

BACKGROUND: The U.S. has experienced an unprecedented number of orders to shelter in place throughout the ongoing COVID-19 pandemic. We aimed to ascertain whether social distancing; difficulty with daily activities; and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of the nation's first shelter-in-place orders (SIPO) among individuals living in the seven affected counties in the San Francisco Bay Area. METHODS: We conducted an online, cross-sectional social media survey from March 14 -April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area versus elsewhere in the U.S. RESULTS: In this non-representative sample, the percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty obtaining hand sanitizer, medications, and in particular respondents reported increased difficulty obtaining food in the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the announcement. CONCLUSION: This study characterizes early changes in attitudes, behaviors, and difficulties. As states and localities implement, rollback, and reinstate shelter-in-place orders, ongoing efforts to more fully examine the social, economic, and health impacts of COVID-19, especially among vulnerable populations, are urgently needed.


Assuntos
Atividades Cotidianas/psicologia , Isolamento de Pacientes/psicologia , Mídias Sociais/estatística & dados numéricos , Adulto , /prevenção & controle , Estudos Transversais , Transmissão de Doença Infecciosa/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Isolamento de Pacientes/tendências , São Francisco/epidemiologia , Estados Unidos/epidemiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-33420416

RESUMO

BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

6.
Int J Cancer ; 148(1): 99-105, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930425

RESUMO

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.

7.
Cancer Epidemiol Biomarkers Prev ; 30(2): 351-363, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33355191

RESUMO

BACKGROUND: Limited studies have investigated racial/ethnic survival disparities for breast cancer 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 breast cancer mortality in 10,366 California women diagnosed with breast cancer from 1993 to 2009. We evaluated joint associations of race/ethnicity, health care, sociodemographic, and lifestyle factors with mortality. RESULTS: Among women with ER/PR+ breast cancer, breast cancer-specific mortality was similar among Hispanic and Asian American women, but higher among African American women [HR, 1.31; 95% confidence interval (CI), 1.05-1.63] compared with non-Hispanic White (NHW) women. Breast cancer-specific mortality was modified by surgery type, hospital type, education, neighborhood socioeconomic status (SES), smoking history, and alcohol consumption. Among African American women, breast cancer-specific mortality was higher among those treated at nonaccredited hospitals (HR, 1.57; 95% CI, 1.21-2.04) and those from lower SES neighborhoods (HR, 1.48; 95% CI, 1.16-1.88) compared with NHW women without these characteristics. Breast cancer-specific mortality was higher among African American women with at least some college education (HR, 1.42; 95% CI, 1.11-1.82) compared with NHW women with similar education. For ER-/PR- disease, breast cancer-specific mortality did not differ by race/ethnicity and associations of race/ethnicity with breast cancer-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- breast cancer. Social determinants and lifestyle factors may explain some of the survival disparities for ER/PR+ breast cancer. IMPACT: Addressing these factors may help reduce the higher mortality of African American women with ER/PR+ breast cancer.

8.
J Natl Cancer Inst ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33301022

RESUMO

BACKGROUND: Clinical guidelines often use predicted lifetime risk from birth to define criteria for making decisions regarding breast cancer screening rather than thresholds based on absolute 5-year risk from current age. METHODS: We used the Prospective Family Cohort Study of 14,657 women without breast cancer at baseline in which, during a median follow-up of 10 years, 482 women were diagnosed with invasive breast cancer. We examined the performances of the IBIS and BOADICEA risk models when using alternative thresholds by comparing predictions based on 5-year risk with those based on lifetime risk from birth and remaining lifetime risk. All statistical tests were two-sided. RESULTS: Using IBIS, the areas under the receiver-operating characteristic curves were 0.66 (95% confidence interval = 0.63 to 0.68) and 0.56 (95% confidence interval = 0.54 to 0.59) for 5-year and lifetime risks, respectively (Pdiff<0.001). For equivalent sensitivities, the 5-year incidence almost always had higher specificities than lifetime risk from birth. For women aged 20-39 years, 5-year risk performed better than lifetime risk from birth. For women aged 40 years or more, receiver-operating characteristic curves were similar for 5-year and lifetime IBIS risk from birth. Classifications based on remaining lifetime risk were inferior to 5-year risk estimates. Results were similar using BOADICEA. CONCLUSIONS: Our analysis shows that risk stratification using clinical models will likely be more accurate when based on predicted 5-year risk compared with risks based on predicted lifetime and remaining lifetime, particularly for women aged 20-39 years.

9.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158149

RESUMO

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

10.
Am J Epidemiol ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128063

RESUMO

Earlier pubertal development is only partially explained by childhood body mass index (BMI); the role of other factors like childhood infections is less understood. Using data from the LEGACY Girls Study (2011 - 2016), we prospectively examined the associations between childhood viral infections (Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Herpes Simplex Virus 1 (HSV1), HSV2 and pubertal timing. We measured exposures based on seropositivity in pre-menarcheal girls (n=490). Breast and pubic hair development were classified based on mother-reported Tanner Stage (TS: TS2+ compared with TS1), adjusting for age, BMI, and sociodemographic factors. The average age at first blood draw was 9.8 years (Stdev=1.9 years). The prevalences were 31% CMV+, 37% EBV+, 14% HSV1+, 0.4% HSV2+, and 16% for both CMV+/EBV+. CMV+ infection without co-infection was associated with developing breasts an average of 7 months earlier (Hazard Ratio (HR)=2.12, 95% CI 1.32, 3.40). CMV+ infection without co-infection and HSV1+ and/or HSV2+ infection were associated with developing pubic hair 9 months later (HR 0.41, 95% CI 0.24, 0.71, HR 0.42, 95% CI 0.22, 0.81, respectively). Infection was not associated with menarche. If replicated in larger cohorts with blood collection prior to any breast development, this study supports that childhood infections may play a role in altering pubertal timing.

11.
Am J Epidemiol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057572

RESUMO

Stressful environments have been associated with earlier menarche. We hypothesized that anxiety, and possibly other internalizing symptoms, are also associated with earlier puberty in girls. The LEGACY Girls Study (2011-2016) includes 1040 girls aged 6 to 13 years at recruitment with growth and development assessed every 6 months. Pre-pubertal maternal reports of daughter's internalizing symptoms were available for breast onset (N=447), pubic hair onset (N=456), and menarche (N=681). Using Cox Proportional Hazard Regression, we estimated prospective hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between one standard deviation of the percentiles of pre-pubertal anxiety, depression, and somatization symptoms and the timing of each pubertal outcome. Multivariable models included age, race/ethnicity, study center, maternal education, body mass index percentile, and breast cancer family history. Additional models included maternal self-reported anxiety. One standard deviation increase of maternally-reported anxiety in girls at baseline was associated with earlier subsequent onset of breast (HR 1.22, 95% CI 1.09-1.36) and pubic hair (HR 1.15, 95% CI 1.01-1.30) development, but not menarche (HR 0.94, 95% CI 0.83-1.07). The association of anxiety with earlier breast development persisted after adjustment for maternal anxiety. Increased anxiety in young girls may indicate risk for earlier pubertal onset.

12.
NPJ Breast Cancer ; 6: 44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964118

RESUMO

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03-6.30, P = 3.1 × 10-9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

13.
Breast ; 54: 62-69, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32927238

RESUMO

OBJECTIVE: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC). METHODS: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity). RESULTS: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast. CONCLUSION: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman's risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.

14.
Nat Commun ; 11(1): 3833, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737321

RESUMO

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Ásia/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Risco
15.
Nat Commun ; 11(1): 3905, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764609

RESUMO

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Ilhas de CpG , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Modelos Genéticos , Fatores de Risco
16.
medRxiv ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32637974

RESUMO

BACKGROUND: The U.S. has experienced an unprecedented number of shelter-in-place orders throughout the COVID-19 pandemic. There is limited empirical research that examines the impact of these orders. We aimed to rapidly ascertain whether social distancing; difficulty with daily activities (obtaining food, essential medications and childcare); and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of shelter-in-place orders for seven counties in the San Francisco Bay Area. METHODS: We conducted an online, cross-sectional social media survey from March 14 - April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area and elsewhere in the U.S. RESULTS: The percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty with obtaining food, hand sanitizer, and medications, particularly with obtaining food for both respondents from the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the shelter-in-place announcement. CONCLUSION: These results capture early changes in attitudes, behaviors, and difficulties. Further research that specifically examines social, economic, and health impacts of COVID-19, especially among vulnerable populations, is urgently needed. =.

17.
JAMA Oncol ; 6(8): 1218-1230, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32614418

RESUMO

Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population. Objective: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers. Design, Setting, and Participants: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. Main Outcomes and Measures: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. Results: Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P < .001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P < .001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P < .001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P < .001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P = .008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P = .001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P = .003) of being a BRCA2 PV carrier. Conclusions and Relevance: Significant differences in the cancer spectrum were observed in male BRCA2, compared with BRCA1, PV carriers. These data may inform future recommendations for surveillance of BRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men with BRCA1/2 PVs.

18.
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.

19.
PLoS One ; 15(6): e0233904, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479509

RESUMO

Racial and ethnic minorities are at higher risk for a variety of diseases. While sociodemographic and lifestyle factors contribute to racial/ethnic health disparities, the biological processes underlying these associations remain poorly understood. Stress and its biological consequences through the glucocorticoid receptor (GR) have been hypothesized to mediate adverse disease outcomes. In fasting morning samples of 503 control women from the San Francisco Bay Area Breast Cancer Study, we used a sensitive Chemical-Activated LUciferase gene eXpression (CALUX) assay to examine the association of sociodemographic and lifestyle factors with plasma glucocorticogenic (G) activity in three racial/ethnic groups. The G activity is a sensitive measure that reflects biological activity of total plasma glucocorticoids including cortisol and glucocorticoid-like compounds. Associations between G activity and sociodemographic and lifestyle factors were examined using multivariable linear regression models. Latina and non-Latina Black (NLB) women had 9% (P = 0.053) and 14% (P = 0.008) lower morning G activity than non-Latina White (NLW) women, respectively. Additionally, we replicated a previously reported association between G activity and alcohol intake (women who drank >10gms had 19% higher G activity than non-drinkers, P = 0.004) in Latina and NLB women. Further research should assess the association between G activity and health outcomes in a prospective cohort so as to characterize the relationship between total plasma G activity in pre-disease state and disease outcomes across different racial/ethnic populations.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Disparidades nos Níveis de Saúde , Estilo de Vida/etnologia , Receptores de Glucocorticoides/sangue , Saúde da Mulher/estatística & dados numéricos , Afro-Americanos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Estudos Prospectivos , São Francisco/epidemiologia , Fatores Socioeconômicos , Inquéritos e Questionários/estatística & dados numéricos
20.
Eur Urol ; 78(3): 316-320, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409115

RESUMO

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

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