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1.
J Cancer Educ ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523407

RESUMO

Growing evidence links adolescent exposures to cancer risk later in life, particularly for common cancers like breast. The adolescent time period is also important for cancer risk reduction as many individual lifestyle behaviors are initiated including smoking and alcohol use. We developed a cancer risk-reduction educational tool tailored for adolescents that focused on five modifiable cancer risk factors. To contextualize risk factors in adolescents' social and physical environments, the intervention also focused on structural barriers to individual- and community-level change, with an emphasis on environmental justice or the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. The educational tool consisted of a 50-min module that included an introduction to cancer biology including genetic susceptibility and environmental interactions, cancer burden in the local community, and risk reduction strategies. The module also included an interactive activity in which adolescent students identify cancer risk factors and brainstorm strategies for risk reduction at both the individual and community level. We administered the module to 12 classes of over 280 high school and college students in New York City. Cancer risk reduction strategies identified by the students included family- or peer-level strategies such as team physical activity and community-level action including improving parks and taxing sugary foods. We developed a novel and interactive cancer risk-reduction education tool focused on multiple cancers that can be adopted by other communities and educational institutions.

2.
Clin Epigenetics ; 13(1): 43, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632303

RESUMO

BACKGROUND: Epigenetic alterations may contribute to early detection of cancer. We evaluated the association of blood DNA methylation with lymphatic-hematopoietic cancers and, for comparison, with solid cancers. We also evaluated the predictive ability of DNA methylation for lymphatic-hematopoietic cancers. METHODS: Blood DNA methylation was measured using the Illumina Infinium methylationEPIC array in 2324 Strong Heart Study participants (41.4% men, mean age 56 years). 788,368 CpG sites were available for differential DNA methylation analysis for lymphatic-hematopoietic, solid and overall cancers using elastic-net and Cox regression models. We conducted replication in an independent population: the Framingham Heart Study. We also analyzed differential variability and conducted bioinformatic analyses to assess for potential biological mechanisms. RESULTS: Over a follow-up of up to 28 years (mean 15), we identified 41 lymphatic-hematopoietic and 394 solid cancer cases. A total of 126 CpGs for lymphatic-hematopoietic cancers, 396 for solid cancers, and 414 for overall cancers were selected as predictors by the elastic-net model. For lymphatic-hematopoietic cancers, the predictive ability (C index) increased from 0.58 to 0.87 when adding these 126 CpGs to the risk factor model in the discovery set. The association was replicated with hazard ratios in the same direction in 28 CpGs in the Framingham Heart Study. When considering the association of variability, rather than mean differences, we found 432 differentially variable regions for lymphatic-hematopoietic cancers. CONCLUSIONS: This study suggests that differential methylation and differential variability in blood DNA methylation are associated with lymphatic-hematopoietic cancer risk. DNA methylation data may contribute to early detection of lymphatic-hematopoietic cancers.

3.
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.

4.
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.

5.
Environ Res ; : 110369, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33131678

RESUMO

BACKGROUND: While animal data support an association between prenatal exposure to endocrine disrupting chemicals (EDCs) and altered mammary gland development and tumorigenesis, epidemiologic studies have only considered a few classes of EDCs in association with pubertal growth and development in girls. Polycyclic aromatic hydrocarbons (PAH) are a class of EDCs that have not been rigorously evaluated in terms of prenatal exposure and pubertal growth and development in girls. OBJECTIVE: In a New York City birth cohort of Black and Hispanic girls (n = 196; recruited 1998-2006), we examined associations of prenatal PAH exposure with self-reported age at growth spurt onset, breast development onset and menarche, and clinical measures of adolescent body composition including body mass index, waist-to-hip ratio, and body fat measured at ages 11-20 years. METHODS: We measured prenatal exposure to PAH using personal air monitoring data collected from backpacks worn by mothers during the third trimester of pregnancy (data available for all 196 girls) and biomarkers of benzo[α]pyrene-DNA adducts in umbilical cord blood (data available for 106 girls). We examined associations of prenatal PAH with the timing of pubertal milestones and adolescent body composition (11-20 years) using multivariable linear regression models adjusted for race/ethnicity, household public assistance status at birth, and age at outcome assessment. We also fit models further adjusted for potential mediators, including birthweight and childhood body size (BMI-for-age z-score measured at 6-8 years). RESULTS: Girls in the highest versus lowest tertile of ambient exposure to PAH, based on a summary measure of eight carcinogenic higher-molecular weight non-volatile PAH compounds (Σ8 PAH), had a 0.90 year delay in growth spurt onset (95% confidence interval (CI) = 0.25, 1.55; n = 196), a 0.35 year delay in breast development onset (95% CI = -0.26, 0.95; n = 193), and a 0.59 year delay in menarche (95% CI = 0.06, 1.11; n = 191) in models adjusted for race/ethnicity and household public assistance at birth. The statistically significant associations for age at growth spurt onset and menarche were not impacted by adjustment for birthweight or childhood body size. No differences in BMI-for-age z-score, waist-to-hip ratio, or percent body fat were found between girls in the highest versus lowest tertile of ambient Σ8 PAH. Results were similar when we evaluated benzo[α]pyrene-DNA adduct levels. DISCUSSION: Our results suggest that prenatal exposure to PAH might delay pubertal milestones in girls, but findings need to be replicated in other cohorts using prospectively collected data on pubertal outcomes.

6.
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.

7.
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.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32998947

RESUMO

BACKGROUND: No study has comprehensively examined how the steroid metabolome is associated with breast cancer risk in women with familial risk. METHODS: We examined 36 steroid metabolites across the spectrum of familial risk (5-year risk ranged from 0.14% to 23.8%) in pre- and postmenopausal women participating in the New York site of the Breast Cancer Family Registry (BCFR). We conducted a nested case-control study with 62 cases/124 controls individually matched on menopausal status, age, and race. We measured metabolites using GC-MS in urine samples collected at baseline before the onset of prospectively ascertained cases. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) per doubling in hormone levels. RESULTS: The average proportion of total steroid metabolites in the study sample were glucocorticoids (61%), androgens (26%), progestogens (11%), and estrogens (2%). A doubling in glucocorticoids (aOR = 2.7; 95% CI = 1.3-5.3) and androgens (aOR = 1.6; 95% CI = 1.0-2.7) was associated with increased breast cancer risk. Specific glucocorticoids (THE, THF αTHF, 6ß-OH-F, THA, and α-THB) were associated with 49% to 161% increased risk. Two androgen metabolites (AN and 11-OH-AN) were associated with 70% (aOR = 1.7; 95% CI = 1.1-2.7) and 90% (aOR = 1.9; 95% CI = 1.2-3.1) increased risk, respectively. One intermediate metabolite of a cortisol precursor (THS) was associated with 65% (OR = 1.65; 95% CI = 1.0-2.7) increased risk. E1 and E2 estrogens were associated with 20% and 27% decreased risk, respectively. CONCLUSIONS: Results suggest that glucocorticoids and 11-oxygenated androgens are positively associated with breast cancer risk across the familial risk spectrum. IMPACT: If replicated, our findings suggest great potential of including steroids into existing breast cancer risk assessment tools.

9.
Breast Cancer Res ; 22(1): 109, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092613

RESUMO

BACKGROUND: Insulin-like growth factor 1 (IGF-1) and binding protein 3 (IGFBP-3) are associated with breast cancer in women at average risk of cancer. Less is known whether these biomarkers also predict risk in women with breast cancer family history. METHODS: We conducted a nested case-control study within the New York site of the Breast Cancer Family Registry (BCFR, n = 80 cases, 156 controls), a cohort enriched for breast cancer family history. Using conditional logistic regression, we estimated the association between IGF-1 and IGFBP-3 levels and breast cancer risk and examined whether this risk differed by predicted absolute breast cancer risk based on pedigree models. RESULTS: The overall association between IGF-1 or IGFBP-3 elevation (≥ median in controls) and breast cancer risk was elevated, but not statistically significant (IGF-1 OR = 1.37, 95% CI = 0.66-2.85; IGFBP-3 OR = 1.62, 95% CI = 0.81-3.24). Women with elevated predicted absolute 10-year risk ≥ 3.4% and elevated IGFBP-3 (≥ median) had more than a 3-fold increased risk compared to women with lower predicted absolute 10-year risk (< 3.4%) and low IGFBP-3 (OR = 3.47 95% CI = 1.04-11.6). CONCLUSIONS: These data offer some support that the overall magnitude of the associations between IGF-1 and IGFBP3 seen in average risk cohorts may be similar in women enriched with a strong breast cancer family history.

10.
Breast Cancer Res ; 22(1): 99, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933550

RESUMO

BACKGROUND: Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. METHODS: Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40-61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported "ever" use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. RESULTS: We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (ß = - 6.56, 95% CI = - 9.05 to - 4.06), and dense area (DA) (ß = - 9.05, 95% CI = - 14.89 to - 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., ß = - 6.86, 95% CI: - 9.67, - 4.05 and ß = - 7.07, 95% CI: - 10.97, - 3.17, respectively, for PD) and higher NDA (ß = 25.05, 95% CI: 14.06, 36.03; ß = 29.76, 95% CI: 14.55, 44.96, respectively). CONCLUSIONS: Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease.

11.
JAMA Netw Open ; 3(8): e2013226, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32804214

RESUMO

Importance: Breast cancer incidence trends by age and race/ethnicity have been documented; it is less clear whether incidence trends of breast cancer molecular subtypes, which differ in risk factors and prognosis, also vary by age and race/ethnicity. Objective: To estimate annual percentage changes and trends in breast cancer molecular subtype-specific incidence rates by age at diagnosis and race/ethnicity in the US. Design, Setting, and Participants: This population-based cross-sectional study included data from 18 cancer registries in the Surveillance, Epidemiology and End Results database, capturing 27.8% of the US population. Hispanic and non-Hispanic White, Black, and Asian/Pacific Islander women aged 25 to 84 years who were diagnosed with invasive breast cancer from 2010 to 2016 were included. Data were analyzed from September 2019 to February 2020. Exposures: Age and racial/ethnic groups. Main Outcomes and Measures: Annual percentage change (APC) and 95% CIs for age-standardized breast cancer incidence rates stratified by 15-year age groups at diagnosis and race/ethnicity. Results: Of 320 124 women diagnosed with breast cancer from 2010 to 2016, 232 558 (72.6%) had luminal A, 35 869 (11.2%) had luminal B, 15 472 (4.8%) had ERBB2-enriched, and 36 225 (11.3%) had triple-negative breast cancer subtypes. Luminal A breast cancer incidence rates increased in non-Hispanic White (APC from 2010-2014, 2.3%; 95% CI, 0.3% to 4.2%) and non-Hispanic Asian/Pacific Islander (APC from 2010-2016, 2.5%; 95% CI, 0.6% to 4.5%) women aged 40 to 54 years, and in non-Hispanic Black women aged 55 to 69 years women (APC from 2010-2012, 4.9%; 95% CI, 4.0% to 5.7%). Luminal B breast cancer incidence rates increased in all age groups for non-Hispanic White women (age 25-39 years: APC, 4.3%; 95% CI, 1.5% to 7.%2; age 40-54 years: APC, 3.5%; 95% CI, 1.4% to 5.6%; age 55-69 years: APC, 3.3%; 95% CI, 1.6% to 5.0%; age 70-84 years: APC, 3.9%; 95% CI, 1.9% to 6.0%) and Hispanic women (age 25-39 years: APC, 8.4%; 95% CI, 5.8% to 11.2%; age 40-54 years: APC, 6.1%; 95% CI, 4.2% to 8.0%; age 55-69 years: APC, 5.1%; 95% CI, 1.5% to 8.8%; age 70-84 years: APC, 7.1%; 95% CI, 4.6% to 9.6%) and in non-Hispanic Asian/Pacific Islander women aged 55 to 69 years (APC, 6.1%; 95% CI, 3.2% to 9.0%). ERBB2-enriched breast cancer incidence rates increased in non-Hispanic White women aged 25 to 39 years (APC, 4.7%; 95% CI, 1.5% to 8.0%). Triple-negative breast cancer incidence rates decreased in non-Hispanic White women aged 40 to 54 years (APC, -2.3%; 95% CI, -3.8% to -0.7%) and 55 to 69 years (APC, -3.6%; 95% CI, -5.1% to -2.1%) and in non-Hispanic Black women aged 55 to 69 years (APC, -1.4%; 95% CI, -2.2% to -0.7%). Conclusions and Relevance: The findings of this cross-sectional study suggest that between 2010 and 2016, luminal A and luminal B breast cancer incidence rates increased for many racial/ethnic and age groups, with the largest increases observed for luminal B breast cancer. ERBB2-enriched breast cancer incidence rates increased for young non-Hispanic White women, while triple-negative breast cancer incidence rates decreased for midlife non-Hispanic White and non-Hispanic Black women. These trends may suggest changes in breast cancer risk factor profiles across age and racial/ethnic groups.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32731638

RESUMO

Measuring systemic chronic inflammatory markers in the blood may be one way of understanding the role of inflammation in breast cancer risk, and might provide an intermediate outcome marker in prevention studies. Here, we present the results of a systematic review of prospective epidemiologic studies that examined associations between systemic inflammatory biomarkers measured in blood and breast cancer risk. From 1 January 2014 to 20 April 2020, we identified 18 unique studies (from 16 publications) that examined the association of systemic inflammatory biomarkers measured in blood with breast cancer risk using prospectively collected epidemiologic data. Only one marker, C-reactive protein, was studied extensively (measured in 13 of the 16 publications), and had some evidence of a positive association with breast cancer risk. Evidence associating other inflammatory biomarkers and more comprehensive panels of markers with the development of breast cancer is limited. Future prospective evidence from expanded panels of systemic blood inflammatory biomarkers is needed to establish strong and independent links with breast cancer risk, along with mechanistic studies to understand inflammatory pathways and demonstrate how breast tissue responds to chronic inflammation. This knowledge could ultimately support the development and evaluation of mechanistically driven interventions to reduce inflammation and prevent breast cancer.


Assuntos
Neoplasias da Mama/epidemiologia , Biomarcadores/metabolismo , Proteína C-Reativa , Feminino , Humanos , Inflamação/epidemiologia , Estudos Prospectivos
13.
Free Radic Res ; 54(6): 431-441, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32686531

RESUMO

Puberty is a time of intense growth and differentiation of breast tissue and a window of susceptibility (WOS) for breast cancer. Although oxidative stress markers have been associated with breast cancer risk, it is unclear whether oxidative stress levels are different during the pubertal WOS, and if so, whether these differences are related to breast cancer susceptibility. We measured urinary biomarkers of whole body oxidative stress (urinary F2-Isoprostanes and 8-oxodeoxyguanosine (8-oxodG)) in 158 girls (ages 6-13 years), 71 with and 87 without a breast cancer family history (BCFH) from a cohort of adolescent girls from the New York site of the LEGACY cohort (Lessons in Epidemiology and Genetics in Adults Cancer from Youth). We compared levels of urinary oxidative stress biomarkers (F2-Isoprostanes and 8-oxodG) across the pubertal window, defined by Tanner Stage (TS) of breast development, both cross-sectionally and longitudinally within girls over an 18-month follow up period. Urinary oxidative stress biomarkers were unrelated to pubertal stages in cross-sectional analyses after considering adjustments for body mass index (BMI) and BCFH. In our longitudinal analysis, we found that urinary 8-oxodG levels, but not F2-Isoprostane levels, increased with age in BCFH + girls (ß = 6.12, 95% CI = 0.08-12.16) compared to BCFH-girls. Higher BMI was associated with higher level of F2-Isoprostane in both cross-sectional (ß = 0.02, 95% CI = 0.0004-0.05) and longitudinal analysis (ß = 0.02, 95% CI = 0.0002-0.05). These findings support that higher BMI increases oxidative stress biomarkers over the pubertal window and that there are changes in 8-oxodG oxidative stress biomarkers in girls with a BCFH compared to girls without a BCFH.

14.
Int J Cancer ; 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32588422

RESUMO

Previous studies have observed a reduced mortality risk associated with menopausal hormone therapy (MHT) use among breast cancer survivors. We sought to clarify whether such association could be explained by tumor heterogeneity, specific causes of death, confounding from comorbidities or health behaviors, and a comparison group of women without breast cancer. We interviewed 1508 women newly diagnosed with first primary breast cancer in 1996 to 1997 (~3 months after diagnosis), and 1556 age-matched women without breast cancer, about MHT use history. The National Death Index was used to ascertain vital status after a median of 17.6 years of follow-up (N = 597 deaths for breast cancer subjects). Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality, and cause-specific HR (cHR) for breast cancer and cardiovascular disease (CVD). The Fine-Gray model was used to account for competing causes of death. Among women with breast cancer, ever vs never MHT use was inversely associated with all-cause (HR = 0.77, 95%CI = 0.62-0.95), breast cancer-specific (cHR = 0.69, 95%CI = 0.48-0.98), and CVD-specific mortality (cHR = 0.57, 95%CI = 0.38-0.85). Difference of the association was observed in breast cancer-specific mortality according to hormone receptor status (negative tumors: cHR = 0.44, 95%CI = 0.19-1.01; positive tumors: cHR = 0.96, 95%CI = 0.60-1.53). Among the comparison group, we observed similar, but more modest inverse associations for all-cause and CVD-specific mortality. MHT use was inversely associated with mortality after breast cancer, even after accounting for competing causes of death and multiple confounders, and was evident among women without breast cancer. Potential heterogeneity by hormone receptor status requires more study.

15.
JNCI Cancer Spectr ; 4(3): pkaa014, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32455334

RESUMO

Background: Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer. Methods: This population-based study was initiated in 1996-1997 with spot urine samples obtained shortly after diagnosis (mean = 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE1 and 16-OHE1 using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n = 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided. Results: Urinary concentrations of the 2-OHE1 to 16-OHE1 ratio (>median of 1.8 vs ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95% CI = 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95% CI = 0.45 to 1.17) and cardiovascular diseases mortality (HR = 0.76, 95% CI = 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n = 118, HR = 0.42, 95% CI = 0.22 to 0.81) than among those who had not (n = 559, HR = 0.98, 95% CI = 0.72 to 1.34; P interaction = .008). Conclusions: The urinary 2-OHE1 to 16-OHE1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection.

16.
Environ Res ; 187: 109346, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32445942

RESUMO

BACKGROUND: The evidence evaluating environmental chemical exposures (ECE) and breast cancer (BC) risk is heterogeneous which may stem in part as few studies measure ECE during key BC windows of susceptibility (WOS). Another possibility may be that most BC studies are skewed towards individuals at average risk, which may limit the ability to detect signals from ECE. OBJECTIVES: We reviewed the literature on ECE and BC focusing on three types of studies or subgroup analyses based on higher absolute BC risk: BC family history (Type 1); early onset BC (Type 2); and/or genetic susceptibility (Type 3). METHODS: We systematically searched the PubMed database to identify epidemiologic studies examining ECE and BC risk published through June 1, 2019. RESULTS: We identified 100 publications in 56 unique epidemiologic studies. Of these 56 studies, only 2 (3.6%) were enriched with BC family history and only 11% of studies (6/56) were specifically enriched with early onset cases. 80% of the publications from these 8 enriched studies (Type 1: 8/10 publications; Type 2: 8/10 publications) supported a statistically significant association between ECE and BC risk including studies of PAH, indoor cooking, NO2, DDT; PCBs, PFOSA; metals; personal care products; and occupational exposure to industrial dyes. 74% of Type 3 publications (20/27) supported statistically significant associations for PAHs, traffic-related air pollution, PCBs, phthalates, and PFOSAs in subgroups of women with greater genetic susceptibility due to variants in carcinogen metabolism, DNA repair, oxidative stress, cellular apoptosis and tumor suppressor genes. DISCUSSION: Studies enriched for women at higher BC risk through family history, younger age of onset and/or genetic susceptibility consistently support an association between an ECE and BC risk. In addition to measuring exposures during WOS, designing studies that are enriched with women at higher absolute risk are necessary to robustly measure the role of ECE on BC risk.


Assuntos
Neoplasias da Mama , Exposição Ambiental , Poluentes Ambientais , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Culinária , Poluentes Ambientais/toxicidade , Feminino , Humanos , Bifenilos Policlorados , Hidrocarbonetos Policíclicos Aromáticos
17.
Eur J Gastroenterol Hepatol ; 32(7): 821-826, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32243343

RESUMO

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) are increasing in adults under 50 years. Risk factors associated with early-onset colorectal neoplasia (CRN) are uncertain. We aimed to identify clinical predictors associated with the presence of CRN detected by diagnostic colonoscopy in symptomatic individuals under 50 years of age. METHODS: We used a single-center endoscopy database to identify symptomatic patients 18-49 years of age who underwent ambulatory colonoscopy between 2007 and 2017. Pathology reports identified CRN as adenomas, advanced adenomas (based on size or histology), or adenocarcinomas. Multivariable analysis was used to determine factors associated with CRN. RESULTS: We identified 4333 eligible patients of whom 363 (8.4%) had any CRN and 48 (1.1%) had advanced neoplasia (advanced adenoma or adenocarcinoma). Factors associated with any CRN on multivariable analysis included male sex [odds ratio (OR) 1.50 (1.19-1.88)], older age group [compared to 18-29 years, OR for 30-39: 3.12 (1.93-5.04); OR for 40-49: 4.68 (2.97-7.36)], obesity [OR for BMI 30-34.9 compared to 18-24.9: 1.44 (1.04-2.01)], and any tobacco use [OR 1.63 (1.18-2.23)]. Anemia was associated with advanced neoplasia [OR 3.11 (1.32-7.34)]. Of the advanced neoplastic lesions, 38 of 48 (79.2%) were located in the distal colon. CONCLUSIONS: In the largest study to date of symptomatic individuals under 50 years of age undergoing colonoscopy in the USA, advanced CRN was most often detected in the distal colon and was associated with anemia, but not with abnormal bowel habits or abdominal pain. We also found that patients with CRN under 50 years of age were more likely to be male, smokers, and obese. These findings should prompt further investigation of these risk factors alone and in combination.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32260163

RESUMO

Migration to the U.S. has been associated with increased body size and obesity risk in Latinas, but results for Caribbean immigrant women are limited and inconclusive. Emerging evidence also suggests that early-life environment associations with women's midlife body mass index (BMI) may be different for larger and smaller women, but this has not been tested within migration life-course history. We examined the associations of nativity and migration timing with midlife body size in a sample of majority Caribbean Latinas and whether these associations varied across the body size distribution. We used interview data from 787 self-identified Latinas (ages 40-65 years) and assessed overall obesity using BMI (kg/m2) and central obesity based on waist circumference (WC, cm). We used linear and quantile regression to examine the association of migration history with BMI and WC and logistic regression for the probability of obesity. Foreign birthplace, later migration age, and lower percent of life in the U.S. were associated with lower BMI and WC means and lower odds of overall and central obesity. Quantile regression showed only inverse associations in the upper quantiles of BMI and WC. For example, relative to U.S.-born women, women living <50% of their lives in the U.S. had lower BMI in the 75th BMI percentile (ß = -4.10, 95% CI: -6.75, -0.81), with minimal differences in the 25th (ß = 0.04, 95% CI: -1.01, 0.96) and 50th BMI percentiles (ß = -1.54, 95% CI: -2.90, 0.30). Our results support that migration to and increasing time in the U.S. are associated with greater body size in midlife Latina women, with stronger influences at higher body size distribution.


Assuntos
Índice de Massa Corporal , Hispano-Americanos , Adulto , Fatores Etários , Idoso , Região do Caribe/etnologia , Emigrantes e Imigrantes , Feminino , Humanos , Pessoa de Meia-Idade , Cidade de Nova Iorque , Fatores de Tempo , Circunferência da Cintura , Adulto Jovem
19.
J Genet Couns ; 29(2): 247-258, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32157769

RESUMO

Focusing screening and treatment to those most likely to benefit is the promise of precision medicine but inequitable distribution of precision medicine innovations may exacerbate health disparities. We investigated whether complex genomic concepts can be successfully communicated to diverse populations. Incorporating principles of Community-based Participatory Research, we created a precision medicine curriculum tailored to the needs of our predominantly Hispanic community. We administered the curriculum over 26 months, assessed pre- and post-test comprehension of 8 genetics-related terms, and compared comprehension differences based on demography and health literacy. In total, 438 individuals completed pre-/post-test assessments. At pre-test, 45.6% scored ≥75% across eight major constructs; 66.7% at post-test. Comprehension increased for 7/8 terms with greatest pre/post-test increases for 'mutation' (55% to 78%) and 'sporadic' (34% to 59%). Mean pre-test comprehension scores (≥75%) were lower for Spanish versus. English speakers; mean post-test scores were equivalent. No heterogeneity by demographics or health literacy was observed. We demonstrate that a brief community educational program can improve knowledge of complex genomic concepts. Interventions to increase understanding of genomic concepts underlying precision medicine are key to patients making informed treatment and prevention decisions and may lead to more equitable uptake of precision medicine initiatives.

20.
Epidemiology ; 31(4): 595-598, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32221269

RESUMO

BACKGROUND: Recent studies have reported substantial increases in cancer incidence in young adults under 40 years in the United States. METHODS: We applied hierarchical cluster analysis to identify cancer anatomical clustering, for 48 anatomic sites, using incidence trends since 1973 for 25- to 39-year-olds. RESULTS: Temporal trends mapped to three major clusters in men involving six organ systems (digestive, endocrine, urinary, blood, respiratory, and male genital) and one cluster in women involving five systems (digestive, endocrine, urinary, female genital, central nervous system). For both men and women, kidney, thyroid, and colorectal cancers consistently clustered for all ages 25-39 and for each 5-year age subgroup. Further, several cancers linked to the endocrine and digestive systems (three in men and six in women) had highly consistent temporal incidence trends. CONCLUSIONS: These findings suggest that there may be organ system connections for cancers of the endocrine and digestive systems; etiologic approaches focused on clusters of cancers rather than individual cancers may prove fruitful.

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