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This study bridges gaps in air pollution research by examining exposure dynamics in disadvantaged communities. Using cutting-edge machine learning and massive data processing, we produced high-resolution (100 meters) daily air pollution maps for nitrogen dioxide (NO 2 ), fine particulate matter (PM 2.5 ), and ozone (O 3 ) across California for 2012-2019. Our findings revealed opposite spatial patterns of NO 2 and PM 2.5 to that of O 3 . We also identified consistent, higher pollutant exposure for disadvantaged communities from 2012 to 2019, although the most disadvantaged communities saw the largest NO 2 and PM 2.5 reductions and the advantaged neighborhoods experienced greatest rising O 3 concentrations. Further, day-to-day exposure variations decreased for NO 2 and O 3 . The disparity in NO 2 exposure decreased, while it persisted for O 3 . In addition, PM 2.5 showed increased day-to-day variations across all communities due to the increase in wildfire frequency and intensity, particularly affecting advantaged suburban and rural communities.

Previous studies of air pollution and respiratory disease often relied on aggregated or lagged acute respiratory disease outcome measures, such as emergency department (ED) visits or hospitalizations, which may lack temporal and spatial resolution. This study investigated the association between daily air pollution exposure and respiratory symptoms among participants with asthma and chronic obstructive pulmonary disease (COPD), using a unique dataset passively collected by digital sensors monitoring inhaled medication use. The aggregated dataset comprised 456,779 short-acting beta-agonist (SABA) puffs across 3,386 people with asthma or COPD, between 2012 and 2019, across the state of California. Each rescue use was assigned space-time air pollution values of nitrogen dioxide (NO 2 ), fine particulate matter with diameter ≤ 2.5 µm (PM 2.5 ) and ozone (O 3 ), derived from highly spatially resolved air pollution surfaces generated for the state of California. Statistical analyses were conducted using linear mixed models and random forest machine learning. Results indicate that daily air pollution exposure is positively associated with an increase in daily SABA use, for individual pollutants and simultaneous exposure to multiple pollutants. The advanced linear mixed model found that a 10-ppb increase in NO 2 , a 10 μg m -3 increase in PM 2.5 , and a 30-ppb increase in O 3 were respectively associated with incidence rate ratios of SABA use of 1.025 (95 % CI: 1.013-1.038), 1.054 (95 % CI: 1.041-1.068), and 1.161 (95 % CI: 1.127-1.233), equivalent to a respective 2.5 %, 5.4 % and 16 % increase in SABA puffs over the mean. The random forest machine learning approach showed similar results. This study highlights the potential of digital health sensors to provide valuable insights into the daily health impacts of environmental exposures, offering a novel approach to epidemiological research that goes beyond residential address. Further investigation is warranted to explore potential causal relationships and to inform public health strategies for respiratory disease management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All co-authors affirm the absence of any conflict of interest related to this research, with the exception of Meredith Barrett and Vy Vuong, who are employees of ResMed (to which Propeller Health is affiliated) and receive salary and stock., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Use of proton pump inhibitors (PPIs) is a mainstay in treating upper gastrointestinal bleeding (UGIB). However, the beneficial effects of PPIs are not anticipated to extend beyond the duodenum and may actually contribute to the risk of lower gastrointestinal bleeding (LGIB). However, in practice, PPIs are often used for inpatients with LGIB where no benefit exists., Methods: A retrospective chart review was performed on inpatients during a 2-year period at an urban academic teaching hospital. Inpatients with consults to the gastroenterology (GI) service with confirmed or highly suspected LGIB were included. Outcomes regarding PPI use and the GI consulting service recommendations in these 225 patients were evaluated., Results: About 37.8% of patients were started on a PPI during their inpatient course. Of those, 46% patients started on a PPI had no indication for PPI and 85% had no recommendation by the GI consultants to start a PPI. Of the 85 patients started on PPI, the GI consultants recommended stopping it in two (2.3%) patients. Lastly, 20 patients (9%) were discharged on PPI without an indication for PPI., Conclusion: To our knowledge, this is the first study that looked at the inappropriate utilization of PPIs in patients admitted for LGIBs utilizing GI consultant recommendations. Given the large proportion of patients started on PPI without a clinical indication and continued at discharge and the paucity of GI recommendations to discontinue inappropriate use, we found that clinical care may be improved with formal GI recommendations regarding use of PPI.

Background: Police brutality towards racially minoritized populations is structural racism. Even though most of the research on the health impacts of police brutality centers the experiences of men, women are also harmed by this structural violence., Objectives: We identify factors associated with the anticipatory stress of police brutality among women and examine its relationship with depressed mood across ethno-racial categories., Methods: Data came from the cross-sectional Survey of the Health of Urban Residents in the United States (N = 2796). Logistic regressions were used to identify factors associated with odds of always worrying about the possibility of becoming a victim of police brutality and to examine its association with depression among Latinas, Black, and White women., Results: Odds of always worrying about police brutality were greater among Black women and Latinas compared to White women. Household history of incarceration was associated with anticipation of police brutality among Black women and Latinas but not among White women. Black women and Latinas with constant anticipation of police brutality and history of incarceration of a household member during their childhood had elevated odds of depressed mood., Conclusion: Although police brutality harms all women, the stressful anticipation of police brutality does not burden all women equally. Structural racism in communities of color continues to be associated with the anticipatory stress of police brutality and it harms the mental health of women of color. Developing policies to eliminate structural racism and for the allocation of resources to persons who are strongly impacted by these injustices is important., (© 2022. W. Montague Cobb-NMA Health Institute.)

Recent guidelines recommend screening for patients with chronic gastroesophageal reflux disease who have three or more additional risk factors for Barrett's esophagus (BE). Failure to screen high-risk individuals represents a missed opportunity in esophageal adenocarcinoma prevention and early detection. We aimed to determine the frequency of upper endoscopy and prevalence of BE and esophageal cancer in a cohort of United States veterans who possessed four or more risk factors for BE. All patients at VA New York Harbor Healthcare System with at least four risk factors for BE between 2012 and 2017 were identified. Procedure records were reviewed for upper endoscopies performed between January 2012 and December 2019. Multivariable logistic regression was used to determine risk factors associated with undergoing endoscopy and factors associated with BE and esophageal cancer. 4505 patients with at least four risk factors for BE were included. 828 patients (18.4%) underwent upper endoscopy, of which 42 (5.1%) were diagnosed with BE and 11 (1.3%) with esophageal cancer (10 adenocarcinoma; 1 squamous cell carcinoma). Among individuals who underwent upper endoscopy, risk factors associated with undergoing endoscopy included obesity (OR, 1.79; 95% CI, 1.41-2.30; P < 0.001) and chronic reflux (OR, 3.86; 95% CI, 3.04-4.90; P < 0.001). There were no individual risk factors associated with BE or BE/esophageal cancer. In this retrospective analysis of patients with 4 or more risk factors for BE, fewer than one-fifth of patients underwent upper endoscopy, supporting the need for efforts aimed at improving BE screening rates., (Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus 2023.)

Building on historical and contemporary efforts to eliminate police and other forms of state violence, and on the understanding that police violence is a social determinant of health, we conducted a systematic review in which we synthesize the existing literature around 1) racial disparities in police violence; 2) health impacts of direct exposure to police violence; and 3) health impacts of indirect exposure to police violence. We screened 336 studies and excluded 246, due to not meeting our inclusion criteria. Forty-eight additional studies were excluded during the full text review, resulting in a study sample size of 42 studies. Our review showed that Black people in the US are far more likely than white people to experience a range of forms of police violence: from fatal and nonfatal shootings, to assault and psychological violence. Exposure to police violence increases risk of multiple adverse health outcomes. Moreover, police violence may operate as a vicarious and ecological exposure, producing consequences beyond those directly assaulted. In order to successfully eliminate police violence, scholars must work in alignment with social justice movements., (Published by Elsevier Ltd.)

Background: Interventions to promote physical activity among women breast cancer survivors (BCS) in low- to middle-income countries are limited. We assessed the acceptability and preliminary effectiveness of a theory-driven, group-based dance intervention for BCS delivered in Bogotá, Colombia., Methods: We conducted a quasi-experimental study employing a mixed-methods approach to assess the 8-week, 3 times/week group dance intervention. The effect of the intervention on participants' physical activity levels (measured by accelerometry), motivation to engage in physical activity, and quality of life were evaluated using generalized estimating equation analysis. The qualitative method included semi-structured interviews thematically analyzed to evaluate program acceptability., Results: Sixty-four BCS were allocated to the intervention (n = 31) or the control groups (n = 33). In the intervention arm, 84% attended ≥ 60% of sessions. We found increases on average minutes of moderate-to-vigorous physical activity per day (intervention: +8.99 vs control: -3.7 min), and in ratings of motivation (intervention change score = 0.45, vs. control change score= -0.05). BCS reported improvements in perceived behavioral capabilities to be active, captured through the interviews., Conclusions: The high attendance, behavioral changes, and successful delivery indicate the potential effectiveness, feasibility, and scalability of the intervention for BCS in Colombia., Trial Registration: ClinicalTrial.gov NCT05252780, registered on Dec 7th, 2021-retrospectively registered unique protocol ID: P20CA217199-9492018., (© 2023. The Author(s).)

Police brutality harms women. Structural racism and structural sexism expose women of color to police brutality through 4 interrelated mechanisms: (1) desecration of Black womanhood, (2) criminalization of communities of color, (3) hypersexualization of Black and Brown women, and (4) vicarious marginalization. We analyze intersectionality as a framework for understanding racial and gender determinants of police brutality, arguing that public health research and policy must consider how complex intersections of these determinants and their contextual specificities shape the impact of police brutality on the health of racially minoritized women. We recommend that public health scholars (1) measure and analyze multiple sources of vulnerability to police brutality, (2) consider policies and interventions within the contexts of intersecting statuses, (3) center life course experiences of marginalized women, and (4) assess and make Whiteness visible. People who hold racial and gender power-who benefit from racist and sexist systems-must relinquish power and reject these benefits. Power and the benefits of power are what keep oppressive systems such as racism, sexism, and police brutality in place. ( Am J Public Health . 2023;113(S1):S29-S36. https://doi.org/10.2105/AJPH.2022.307064).

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

On February 26, 2012, a Black child, Trayvon Martin, was executed in Sanford, Florida. Seventeen months later his killer was found not guilty. This is but one example of the state's brazen disregard for Black life, rooted in the kidnapping and enslavement of Africans more than 400 years ago, and the ways in which they and their descendants were systematically tortured. Trayvon Martin's murder catalyzed the Black Lives Matter (BLM) movement, which names and resists deeply entrenched state violence and inequities against Black people in the U.S. In this manuscript we: (1) summarize examples of structural disregard for Black lives in the U.S.; (2) describe how this disregard is reflected in differential patterns of social inequities, morbidity, and mortality; and (3) discuss how we can better employ the BLM perspective to frame a more historicized understanding of patterns in population health and to envision ways to resist health inequities.

More than 600,000 incarcerated individuals are released annually in the United States; a large proportion are Black men incarcerated for drug-related offenses, including drug use and possession. Formerly incarcerated Black men report elevated rates of condomless sex and sexually transmitted infections, including human immunodeficiency virus (HIV). The purpose of this study was to explore condom usage among Black men who were formerly incarcerated for drug-related offenses and living in New York City (NYC). Using a semi-structured interview guide, in-depth interviews were conducted with 26 formerly incarcerated Black men. Interviews were audio-recorded, transcribed, and entered into NVivo, then manually coded utilizing thematic analysis methods. The following four themes were identified: partner type and length of the relationship affected condom use; diminished pleasure was a barrier for condom use; challenges with ill-fitting and poor-quality condoms; and the withdrawal method was used as an HIV prevention technique. Our findings suggest that formerly incarcerated Black men are engaging in condomless sex post-incarceration. Greater exposure to prevention messages and targeted interventions with content that includes interpersonal and condom use skill-building, methods to increase pleasurable condom use, information on HIV and STI transmission modes, and access to pre-exposure prophylaxis (PrEP) may be beneficial for this population.

Emerging data suggest that circulating tumor DNA (ctDNA) can detect colorectal cancer (CRC)-specific signals across both non-metastatic and metastatic settings. With the development of multiple platforms, including tumor-informed and tumor-agnostic ctDNA assays and demonstration of their provocative analytic performance to detect minimal residual disease, there are now ongoing, phase III randomized clinical trials to evaluate their role in the management paradigm of CRC. In this review, we highlight landmark studies that have formed the basis for ongoing studies on the clinically applicability of plasma ctDNA assays in resected, stage I-III CRC and metastatic CRC. We discuss clinical settings by which ctDNA may have the most immediate impact in routine clinical practice. These include the potential for ctDNA to (1) guide surveillance and intensification or de-intensification strategies of adjuvant therapy in resected, stage I-III CRC, (2) predict treatment response to neoadjuvant therapy in locally advanced rectal cancer inclusive of total neoadjuvant therapy (TNT), and (3) predict response to systemic and surgical therapies in metastatic disease. We end by considering clinical variables that can influence our ability to reliably interpret ctDNA dynamics in the clinic.

Background: In the U.S., approximately one in seven HIV-infected individuals experience incarceration at least once in their lifetime. While HIV-infected individuals experience positive health outcomes during periods of incarceration, they tend to experience treatment disruption as they return to their community after custody which results in poor health outcomes. The purpose of this study was to explore the transitional support received from the Department of Corrections during the reentry period., Methods: We conducted in-depth interviews with 20 HIV-infected formerly incarcerated individuals in New York City. Interviews were audio recorded and transcribed. Three researchers performed line-by-line reading of the transcripts to identify dominant codes and themes that emerged. A mixture of deductive and inductive techniques was used to identify patterns that emerged in the data., Results: Most of the participants were male and racial and ethnic minorities. There were five dominant themes that emerged during our analysis: 1) variations in the quantity of antiretroviral medication received during transition; 2) linkages to community-based physical health care providers was not well-coordinated; 3) insufficient housing and social resources; 4) structural and social challenges to post-release well-being; and 5) family as a source of resilience., Conclusions: Discharge support planning should include sufficient medication to prevent treatment disruption and a more comprehensive approach to linkage to community-based healthcare services. Such planning should also include thorough pre-release assessments to identify appropriate levels of support needed, including employment and housing assistance, which will be useful for resource allocation. Broadening public health partnerships may also increase availability and promote accessibility to the most appropriate healthcare services and programs, which may provide better opportunities to receive coordinated care and ensure continuity of care. Finally, ties to family members and other loved ones should be leveraged to help facilitate the achievement of optimal health outcomes among this population.

Experimental, observational, and clinical trials support a critical role of folate one-carbon metabolism (FOCM) in colorectal cancer (CRC) development. In this report, we focus on understanding the relationship between common genetic variants and metabolites of FOCM. We conducted a genome-wide association study of FOCM biomarkers among 1,788 unaffected (without CRC) individuals of European ancestry from the Colon Cancer Family Registry. Twelve metabolites, including 5-methyltetrahydrofolate, vitamin B 2 (flavin mononucleotide and riboflavin), vitamin B 6 (4-pyridoxic acid, pyridoxal, and pyridoxamine), total homocysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, cystathionine, and creatinine were measured from plasma using liquid chromatography-mass spectrometry (LC-MS) or LC-MS/MS. For each individual biomarker, we estimated genotype array-specific associations followed by a fixed-effect meta-analysis. We identified the variant rs35976024 (at 2p11.2 and intronic of ATOH8) associated with total homocysteine (p = 4.9 × 10 -8 ). We found a group of six highly correlated variants on chromosome 15q14 associated with cystathionine (all p < 5 × 10 -8 ), with the most significant variant rs28391580 (p = 2.8 × 10 -8 ). Two variants (rs139435405 and rs149119426) on chromosome 14q13 showed significant (p < 5 × 10 -8 ) associations with S-adenosylhomocysteine. These three biomarkers with significant associations are closely involved in homocysteine metabolism. Furthermore, when assessing the principal components (PCs) derived from seven individual biomarkers, we identified the variant rs12665366 (at 6p25.3 and intronic of EXOC2) associated with the first PC (p = 2.3 × 10 -8 ). Our data suggest that common genetic variants may play an important role in FOCM, particularly in homocysteine metabolism., (© 2019 Wiley Periodicals, Inc.)

Purpose: Lynch syndrome due to pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, and MSH6 is predominantly associated with colorectal and endometrial cancer, although extracolonic cancers have been described within the Lynch tumor spectrum. However, the age-specific cumulative risk (penetrance) of these cancers is still poorly defined for PMS2-associated Lynch syndrome. Using a large data set from a worldwide collaboration, our aim was to determine accurate penetrance measures of cancers for carriers of heterozygous pathogenic PMS2 variants., Methods: A modified segregation analysis was conducted that incorporated both genotyped and nongenotyped relatives, with conditioning for ascertainment to estimates corrected for bias. Hazard ratios (HRs) and corresponding 95% CIs were estimated for each cancer site for mutation carriers compared with the general population, followed by estimation of penetrance., Results: In total, 284 families consisting of 4,878 first- and second-degree family members were included in the analysis. PMS2 mutation carriers were at increased risk for colorectal cancer (cumulative risk to age 80 years of 13% [95% CI, 7.9% to 22%] for males and 12% [95% CI, 6.7% to 21%] for females) and endometrial cancer (13% [95% CI, 7.0%-24%]), compared with the general population (6.6%, 4.7%, and 2.4%, respectively). There was no clear evidence of an increased risk of ovarian, gastric, hepatobiliary, bladder, renal, brain, breast, prostate, or small bowel cancer., Conclusion: Heterozygous PMS2 mutation carriers were at small increased risk for colorectal and endometrial cancer but not for any other Lynch syndrome-associated cancer. This finding justifies that PMS2-specific screening protocols could be restricted to colonoscopies. The role of risk-reducing hysterectomy and bilateral salpingo-oophorectomy for PMS2 mutation carriers needs further discussion.

Background: The relationships between neighborhood factors (i.e., neighborhood socioeconomic status (nSES) and ethnic enclave) and histologic subtypes of lung cancer for racial/ethnic groups, particularly Hispanics and Asian American/Pacific Islanders (AAPIs), are poorly understood., Methods: We conducted a population-based study of 75,631 Californians diagnosed with lung cancer from 2008 through2012. We report incidence rate ratios (IRRs) for lung cancer histologic cell-types by nSES among racial/ethnic groups (non-Hispanic (NH) Whites, NH Blacks, Hispanics and AAPIs) and according to Hispanic or Asian neighborhood ethnic enclave status among Hispanics and AAPIs, respectively. In addition, we examined incidence jointly by nSES and ethnic enclave., Results: Patterns of lung cancer incidence by nSES and ethnic enclave differed across race/ethnicity, sex, and histologic cell-type. For adenocarcinoma, Hispanic males and females, residing in both low nSES and high nSES neighborhoods that were low enclave, had higher incidence rates compared to those residing in low nSES, high enclave neighborhoods; males (IRR, 1.17 [95% CI, 1.04-1.32] and IRR, 1.15 [95% CI, 1.02-1.29], respectively) and females (IRR, 1.29 [95% CI, 1.15-1.44] and IRR, 1.51 [95% CI, 1.36-1.67], respectively). However, AAPI males residing in both low and high SES neighborhoods that were also low enclave had lower adenocarcinoma incidence., Conclusions: Neighborhood factors differentially influence the incidence of lung cancer histologic cell-types with heterogeneity in these associations by race/ethnicity and sex. For Hispanic males and females and AAPI males, neighborhood ethnic enclave status is strongly associated with lung adenocarcinoma incidence., Competing Interests: C.A. Clarke is currently a Population Health Scientist at GRAIL, Inc; this does not alter our adherence to PLOS ONE policies on sharing data and materials. No potential conflicts of interest were disclosed by the other authors.

BACKGROUND Intracardiac abscesses are an unusual occurrence in developed countries. With the increase in use of implantable cardiac devices, the increase use of and advancements in antibiotics, and the longevity of patients with cardiac devices, one may expect an increase in such infections; however, case reports are rare. We are presenting a case in which hematogenous dissemination of methicillin-sensitive Staphylococcus aureus (MSSA) infection from a lower extremity diabetic ulcer propagated into an infected pacemaker lead and ultimately an intracardiac abscess of the right atrium. CASE REPORT A 77-year-old male with a history of MSSA diabetic foot infection complicated by osteomyelitis presented with fever, syncope, and wide complex tachycardia, and he was found to have an intracardiac abscess and fibrinous lead vegetations. The patient was deemed too ill for invasive surgical intervention given his comorbidities, pacemaker generator replacement requirement, and intermittent ventricular tachycardia. The patient was subsequently sent home with oral antibiotics and home hospice per patient and family wishes. CONCLUSIONS This case demonstrated how hematogenous dissemination of MSSA infections from a diabetic foot ulcer and osteomyelitis can seed pacemaker hardware resulting in an intracardiac abscess. Unfortunately, our patient was too ill to undergo all procedures required to eradicate the abscess and infected pacemaker hardware. The standard of care would be complete hardware removal. Conservative management would include indefinite or prolonged antibiotic therapy, with the notion that intracardiac abscesses cannot be cured with antibiotics alone. This conservative management approach would be deemed necessary in a select population that cannot undergo surgical intervention.

Importance: There have been substantial improvements in the early detection, treatment, and survival from cancer in the United States, but it is not clear to what extent patients with different types of health insurance have benefitted from these advancements., Objective: To examine trends in cancer survival by health insurance status from January 1997 to December 2014., Design, Setting, and Participants: California Cancer Registry (a statewide cancer surveillance system) data were used to estimate population-based survival by health insurance status in 3 calendar periods: January 1997 to December 2002, January 2003 to December 2008, and January 2009 to December 2014 with follow-up through 2014. Overall, 1 149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or melanoma in California were included in the study., Main Outcomes and Measures: Five-year all-cause and cancer-specific survival probabilities by insurance category and calendar period for each cancer site and sex; hazard ratios (HRs) and 95% CIs for each insurance category (none, Medicare, other public) compared with private insurance in each calendar period., Results: According to data from 1 149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or melanoma gathered from the California Cancer Registry, improvements in survival were almost exclusively limited to patients with private or Medicare insurance. For patients with other public or no insurance, survival was largely unchanged or declined. Relative to privately insured patients, cancer-specific mortality was higher in uninsured patients for all cancers except prostate, and disparities were largest from 2009 to 2014 for breast (HR, 1.72; 95% CI, 1.45-2.03), lung (men: HR, 1.18; 95% CI, 1.06-1.31 and women: HR, 1.32; 95% CI, 1.15-1.50), and colorectal cancer (women: HR, 1.30; 95% CI, 1.05-1.62). Mortality was also higher for patients with other public insurance for all cancers except lung, and disparities were largest from 2009 to 2014 for breast (HR, 1.25; 95% CI, 1.17-1.34), prostate (HR, 1.17; 95% CI, 1.04-1.31), and colorectal cancer (men: HR, 1.16; 95% CI, 1.08-1.23 and women: HR, 1.11; 95% CI, 1.03-1.20)., Conclusions and Relevance: After accounting for patient and clinical characteristics, survival disparities for men with prostate cancer and women with lung or colorectal cancer increased significantly over time, reflecting a lack of improvement in survival for patients with other public or no insurance. To mitigate these growing disparities, all patients with cancer need access to health insurance that covers all the necessary elements of health care, from prevention and early detection to timely treatment according to clinical guidelines.

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk.

Background: Private health insurance is associated with improved outcomes in patients with cancer. However, to the authors' knowledge, little is known regarding the impact of the Patient Protection and Affordable Care Act Dependent Coverage Expansion (ACA-DCE), which extended private insurance to young adults (to age 26 years) beginning in 2010, on the insurance status of young adults with cancer., Methods: The current study was a retrospective, population-based analysis of hospitalized young adult oncology patients (aged 22-30 years) in California during 2006 through 2014 (11,062 patients). Multivariable regression analyses examined factors associated with having private insurance. Results were presented as adjusted odds ratios and 95% confidence intervals. A difference-in-difference analysis examined the influence of the ACA-DCE on insurance coverage by race/ethnicity and federal poverty level., Results: Multivariable regression demonstrated that patients of black and Hispanic race/ethnicity were less likely to have private insurance before and after the ACA-DCE, compared with white patients. Younger age (22-25 years) was associated with having private insurance after implementation of the ACA-DCE (odds ratio, 1.20; 95% confidence interval, 1.06-1.35). In the difference-in-difference analysis, private insurance increased among white patients aged 22 to 25 years who were living in medium-income (2006-2009: 64.6% vs 2011-2014: 69.1%; P = .003) and high-income (80.4% vs 82%; P = .043) zip codes and among Asians aged 22 to 25 years living in high-income zip codes (73.2 vs 85.7%; P = .022). Private insurance decreased for all Hispanic patients aged 22 to 25 years between the 2 time periods., Conclusions: The ACA-DCE provision increased insurance coverage, but not among all patients. Private insurance increased for white and Asian patients in higher income neighborhoods, potentially widening social disparities in private insurance coverage among young adults with cancer. Cancer 2018;124:110-7. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose Racial/ethnic disparities in cancer survival in the United States are well documented, but the underlying causes are not well understood. We quantified the contribution of tumor, treatment, hospital, sociodemographic, and neighborhood factors to racial/ethnic survival disparities in California. Materials and Methods California Cancer Registry data were used to estimate population-based cancer-specific survival for patients diagnosed with breast, prostate, colorectal, or lung cancer between 2000 and 2013 for each racial/ethnic group (non-Hispanic black, Hispanic, Asian American and Pacific Islander, and separately each for Chinese, Japanese, and Filipino) compared with non-Hispanic whites. The percentage contribution of factors to overall racial/ethnic survival disparities was estimated from a sequence of multivariable Cox proportional hazards models. Results In baseline models, black patients had the lowest survival for all cancer sites, and Asian American and Pacific Islander patients had the highest, compared with whites. Mediation analyses suggested that stage at diagnosis had the greatest influence on overall racial/ethnic survival disparities accounting for 24% of disparities in breast cancer, 24% in prostate cancer, and 16% to 30% in colorectal cancer. Neighborhood socioeconomic status was an important factor in all cancers, but only for black and Hispanic patients. The influence of marital status on racial/ethnic disparities was stronger in men than in women. Adjustment for all covariables explained approximately half of the overall survival disparities in breast, prostate, and colorectal cancer, but it explained only 15% to 40% of disparities in lung cancer. Conclusion Overall reductions in racial/ethnic survival disparities were driven largely by reductions for black compared with white patients. Stage at diagnosis had the largest effect on racial/ethnic survival disparities, but earlier detection would not entirely eliminate them. The influences of neighborhood socioeconomic status and marital status suggest that social determinants, support mechanisms, and access to health care are important contributing factors.

Background: Adolescents and young adults (AYAs) ages 15 to 39 years with cancer continue to experience disparate survival outcomes compared with their younger and older counterparts. This may be caused in part by differential access to specialized cancer centers (SCCs), because treatment at SCCs has been associated with improved overall survival. The authors examined social and clinical factors associated with AYA use of SCCs (defined as Children's Oncology Group-designated or National Cancer Institute-designated centers)., Methods: A retrospective, population-based analysis was performed on all hospital admissions of AYA oncology patients in California during 1991 through 2014 (n = 127,250) using the Office of Statewide Health Planning and Development database. Multivariable logistic regression analyses examined the contribution of social and clinical factors on always receiving care from an SCC (vs sometimes or never). Results are presented as adjusted odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Over the past 20 years, the percentage of patients always receiving inpatient care at an SCC increased over time (from 27% in 1991 to 43% in 2014). In multivariable regression analyses, AYA patients were less likely to always receive care from an SCC if they had public insurance (OR, 0.64; 95% CI, 0.62-0.66), were uninsured (OR, 0.51; 95% CI, 0.46-0.56), were Hispanic (OR, 0.88; 95% CI, 0.85-0.91), lived > 5 miles from an SCC, or had a diagnosis other than leukemia and central nervous system tumors., Conclusions: Receiving care at an SCC was influenced by insurance, race/ethnicity, geography, and tumor type. Identifying the barriers associated with decreased SCC use is an important first step toward improving outcomes in AYA oncology patients. Cancer 2017;123:2516-23. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Genome-wide association studies (GWAS) in ethnic/racial minority populations can help to fine-map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.3, associated with colon cancer risk (odds ratio 0.61 for the risk allele G, p = 2.4 × 10 -8 ). The frequency of the G allele was 0.06 in African Americans, compared to <0.01 in Europeans, Asians and Amerindians in the 1000 Genomes project. In addition, a variant previously identified through fine-mapping in this GWAS in the region 19q13.1, rs7252505, was confirmed to be more strongly associated with CRC in the African American replication set than the variant originally reported in Europeans (rs10411210). The association between rs7252505 and CRC was of borderline significance (p = 0.05) in a Hispanic population GWAS with 1,611 CRC cases and 4,330 controls. With the three datasets combined, the odds ratio was 0.84 for the risk allele A (95% confidence interval 0.79-0.89, p = 3.7 × 10 -8 ). This study further highlights the importance of conducting GWAS studies in diverse ancestry populations., (© 2017 UICC.)

Objectives: Lung cancer incidence trends by histology, sex, race/ethnicity, and neighborhood socioeconomic status (nSES) have not been previously reported. We conducted a population-based study of lung cancer incidence over three peri-censal periods: 1988-1992, 1998-2002, and 2008-2012., Materials and Methods: We abstracted lung cancer cases from the California Cancer Registry and used US Census and American Community Survey data to develop multidimensional nSES indices for each census period. We calculated nSES tertile-specific incidence rates and rate ratios for each peri-censal period and used incidence rate ratios (IRR) to assess changes in rates from 1988 to 1992 to 1998-2002 and 2008-2012., Results: There were a total of 231,205 lung cancer cases. Males: Among males, incidence rates of lung cancer decreased over time, all race/ethnicities, and all nSES tertiles, with larger declines among males in higher nSES areas. Rates either declined or were stable for adenocarcinoma, with larger declines for other histologic subtypes. Females: Among females, declines in incidence rates of lung cancer were more pronounced for females in higher nSES areas, but diverged more so than for males, with variations by histology and race/ethnicity. Incidence rates of adenocarcinoma increased over time among all females, with greater increase among females in low nSES areas., Conclusions: Our findings demonstrate differences in incidence trends over three decades by histology, gender, race/ethnicity, and nSES. While incidence rates consistently declined over time for males, there were greater declines in incidence for high nSES populations. In contrast, among females, there was evidence of increases in lung cancer incidence among low SES API females, and for adenocarcinoma., (Published by Elsevier B.V.)

Low dose CT (LDCT) for lung cancer screening is an evidence-based, guideline recommended, and Medicare approved test but uptake requires further study. We therefore conducted patient and provider surveys to elucidate factors associated with utilization. Patients referred for LDCT at an academic medical center were questioned about their attitudes, knowledge, and beliefs on lung cancer screening. Adherent patients were defined as those who met screening eligibility criteria and completed a LDCT. Referring primary care providers within this same medical system were surveyed in parallel about their practice patterns, attitudes, knowledge and beliefs about screening. Eighty patients responded (36%), 48 of whom were adherent. Among responders, non-Hispanic patients ( p  = 0.04) were more adherent. Adherent respondents believed that CT technology is accurate and early detection is useful, and they trusted their providers. A majority of non-adherent patients (79%) self-reported an intention to obtain a LDCT in the future. Of 36 of 87 (41%) responding providers, only 31% knew the correct lung cancer screening eligibility criteria, which led to a 37% inappropriate referral rate from 2013 to 2015. Yet, 75% had initiated lung cancer screening discussions, 64% thought screening was at least moderately effective, and 82% were interested in learning more of the 33 providers responding to these questions. Overall, patients were motivated and providers engaged to screen for lung cancer by LDCT. Non-adherent patient "procrastinators" were motivated to undergo screening in the future. Additional follow through on non-adherence may enhance screening uptake, and raising awareness for screening eligibility through provider education may reduce inappropriate referrals.

Background: The incidence of Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, has risen rapidly worldwide. PTC usually has an excellent prognosis. However, the rising incidence of PTC, due at least partially to widespread use of neck imaging studies with increased detection of small cancers, has created a clinical issue of overdiagnosis, and consequential overtreatment. We investigated how molecular data can be used to develop a prognostics signature for PTC., Methods: The Cancer Genome Atlas (TCGA) recently reported on the genomic landscape of a large cohort of PTC cases. In order to decrease unnecessary morbidity associated with over diagnosing PTC patient with good prognosis, we used TCGA data to develop a gene expression signature to distinguish between patients with good and poor prognosis. We selected a set of clinical phenotypes to define an 'extreme poor' prognosis group and an 'extreme good' prognosis group and developed a gene signature that characterized these., Results: We discovered a gene expression signature that distinguished the extreme good from extreme poor prognosis patients. Next, we applied this signature to the remaining intermediate risk patients, and show that they can be classified in clinically meaningful risk groups, characterized by established prognostic disease phenotypes. Analysis of the genes in the signature shows many known and novel genes involved in PTC prognosis., Conclusions: This work demonstrates that using a selection of clinical phenotypes and treatment variables, it is possible to develop a statistically useful and biologically meaningful gene signature of PTC prognosis, which may be developed as a biomarker to help prevent overdiagnosis.

The association between breast cancer and warfarin is inconclusive as most previous studies examined their association using patients with thromboembolism, whereas thromboembolism itself is a risk factor for cancer. We explored this issue using patients received mechanical heart valves replacement as a proxy for warfarin exposure as these patients need a lifelong warfarin treatment, and compared them with patients received bioprosthesis valves replacement (short-term warfarin treatment) in Sweden between 1987 and 2010. Patients who were operated on for valve replacement were identified from the Swedish Hospital Discharge Registry and linked to the Swedish Cancer Registry to examine the hazard ratios of subsequent breast cancer. A total of 12,242 women were operated on for valve replacement (5481 with mechanical valve and 6401 with bioprosthetic valve). For the entire cohort, the HR of breast cancer was 1.49 (95 % CI 1.09-2.02) among patients with mechanical valve replacement compared to those with bioprosthetic valve replacement. After controlling for a number of confounding factors using propensity score weighting, the HR was 1.69 (95 % CI 1.15-2.47). Our study found that patients with mechanical valve replacement have an increased risk of breast cancer compared to those with bioprosthetic valve replacement. If confirmed, this increased risk should be considered when recommending breast cancer screening for women with mechanical valve replacement. Long-term use of warfarin may explain the observed increase. If so, patients who have used warfarin long-term for other reasons should be studied for a possible increased risk of breast cancer.

Black sexual minority women are triply marginalized due to their race, gender, and sexual orientation. We compared three dimensions of discrimination-frequency (regularity of occurrences), scope (number of types of discriminatory acts experienced), and number of bases (number of social statuses to which discrimination was attributed)-and self-reported mental health (depressive symptoms, psychological well-being, and social well-being) between 64 Black sexual minority women and each of two groups sharing two of three marginalized statuses: (a) 67 White sexual minority women and (b) 67 Black sexual minority men. Black sexual minority women reported greater discrimination frequency, scope, and number of bases and poorer psychological and social well-being than White sexual minority women and more discrimination bases, a higher level of depressive symptoms, and poorer social well-being than Black sexual minority men. We then tested and contrasted dimensions of discrimination as mediators between social status (race or gender) and mental health outcomes. Discrimination frequency and scope mediated the association between race and mental health, with a stronger effect via frequency among sexual minority women. Number of discrimination bases mediated the association between gender and mental health among Black sexual minorities. Future research and clinical practice would benefit from considering Black sexual minority women's mental health in a multidimensional minority stress context.

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.

Background: Familial Colorectal Cancer Type X (FCCTX) is defined as individuals with colorectal cancer (CRC) who families meet Amsterdam Criteria-1 (AC1), but whose tumours are DNA-mismatch-repair-proficient, unlike Lynch syndrome (LS). FCCTX does not have an increased risk of extra-colonic cancers. This analysis compares epidemiologic and clinicopathologic features among FCCTX, LS, and 'non-familial' (non-AC1) CRC cases., Methods: From the Colon Cancer Family Registry, FCCTX (n=173), LS (n=303), and non-AC1 (n=9603) CRC cases were identified. Questionnaire-based epidemiologic information and CRC pathologic features were compared across case groups using polytomous logistic regression., Results: Compared with LS, FCCTX cases were less likely to be current (vs never) smokers; have a proximal subsite (vs rectal) tumour; or have mucinous histology, poor differentiation, or tumour-infiltrating lymphocytes. There were no observed differences in co-morbidities or medication usage., Conclusions: FCCTX were less likely to be current tobacco users; other exposures were similar between these groups. Histopathologic differences highly suggestive of LS CRCs do not appear to be shared by FCCTX.

Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC (P < 4 × 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer.

Objectives: Telomeres are nucleoprotein structures that cap the end of chromosomes and shorten with sequential cell divisions in normal aging. Short telomeres are also implicated in the incidence of many cancers, but the evidence is not conclusive for colorectal cancer (CRC). Therefore, the aim of this study was to assess the association of CRC and telomere length., Methods: In this case-control study, we measured relative telomere length from peripheral blood leukocytes (PBLs) DNA with quantitative PCR in 598 CRC patients and 2,212 healthy controls., Results: Multivariate analysis indicated that telomere length was associated with risk for CRC, and this association varied in an age-related manner; younger individuals (≤50 years of age) with longer telomeres (80-99 percentiles) had a 2-6 times higher risk of CRC, while older individuals (>50 years of age) with shortened telomeres (1-10 percentiles) had 2-12 times the risk for CRC. The risk for CRC varies with extremes in telomere length in an age-associated manner., Conclusions: Younger individuals with longer telomeres or older individuals with shorter telomeres are at higher risk for CRC. These findings indicate that the association of PBL telomere length varies according to the age of cancer onset and that CRC is likely associated with at minimum two different mechanisms of telomere dynamics.

Genome-wide association studies of colorectal cancer (CRC) in Europeans and Asians have identified 21 risk susceptibility regions [29 index single-nucleotide polymorphisms (SNPs)]. Characterizing these risk regions in diverse racial groups with different linkage disequilibrium (LD) structure can help localize causal variants. We examined associations between CRC and all 29 index SNPs in 6597 African Americans (1894 cases and 4703 controls). Nine SNPs in eight regions (5q31.1, 6q26-q27, 8q23.3, 8q24.21, 11q13.4, 15q13.3, 18q21.1 and 20p12.3) formally replicated in our data with one-sided P-values <0.05 and the same risk directions as reported previously. We performed fine-mapping of the 21 risk regions (including 250 kb on both sides of the index SNPs) using genotyped and imputed markers at the density of the 1000 Genomes Project to search for additional or more predictive risk markers. Among the SNPs correlated with the index variants, two markers, rs12759486 (or rs7547751, a putative functional variant in perfect LD with it) in 1q41 and rs7252505 in 19q13.1, were more strongly and statistically significantly associated with CRC (P < 0.0006). The average per allele risk was improved using the replicated index variants and the two new markers (odds ratio = 1.14, P = 6.5 × 10(-16)) in African Americans, compared with using all index SNPs (odds ratio = 1.07, P = 3.4 × 10(-10)). The contribution of the two new risk SNPs to CRC heritability was estimated to be 1.5% in African Americans. This study highlights the importance of fine-mapping in diverse populations.

Background: Both shorter and longer telomeres in peripheral blood leukocyte (PBL) DNA have been associated with cancer risk. However, associations remain inconsistent across studies of the same cancer type. This study compares DNA preparation methods to determine telomere length from patients with colorectal cancer., Methods: We examined PBL relative telomere length (RTL) measured by quantitative PCR (qPCR) in 1,033 patients with colorectal cancer and 2,952 healthy controls. DNA was extracted with phenol/chloroform, PureGene, or QIAamp., Results: We observed differences in RTL depending on DNA extraction method (P < 0.001). Phenol/chloroform-extracted DNA had a mean RTL (T/S ratio) of 0.78 (range 0.01-6.54) compared with PureGene-extracted DNA (mean RTL of 0.75; range 0.00-12.33). DNA extracted by QIAamp yielded a mean RTL of 0.38 (range 0.02-3.69). We subsequently compared RTL measured by qPCR from an independent set of 20 colorectal cancer cases and 24 normal controls in PBL DNA extracted by each of the three extraction methods. The range of RTL measured by qPCR from QIAamp-extracted DNA (0.17-0.58) was less than from either PureGene or phenol/chloroform (ranges, 0.04-2.67 and 0.32-2.81, respectively)., Conclusions: RTL measured by qPCR from QIAamp-extracted DNA was less than from either PureGene or phenol/chloroform (P < 0.001)., Impact: Differences in DNA extraction method may contribute to the discrepancies between studies seeking to find an association between the risk of cancer or other diseases and RTL., (©2013 AACR.)

Background: It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways., Methods: In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for more than 600 tagSNPs and 99 single-nucleotide polymorphisms (SNP) were selected for further examination based on strength of association. In the second stage, 351 SNPs tagging gene regions covered by the 99 SNPs were tested in 4,783 Multiethnic Cohort subjects (2,153 cases, 2,630 controls)., Results: The association between rs9858822 in the PPARG gene and colorectal cancer was statistically significant at the end of the second stage (OR per allele = 1.36, Bonferroni-adjusted P = 0.045), based on the "effective" number of markers in stage II (n = 306). The risk allele C was common (frequency 0.3) in African Americans but rare (frequency < 0.03) in whites, Japanese Americans, Latinos, and Native Hawaiians. No statistically significant heterogeneity of effects across race/ethnicity, body mass index (BMI) levels, regular aspirin use, or pack-years of smoking was detected for this SNP. Suggestive associations were also observed for several SNPs in close vicinity to rs9858822., Conclusions: Our results provide new evidence of association between PPARG variants and colorectal cancer risk., Impact: Further replication in independent samples is warranted., (©2013 AACR.)

Current screening practices have been able to identify PMS2 mutations in 78 % of cases of colorectal cancer from the Colorectal Cancer Family Registry (Colon CFR) which showed solitary loss of the PMS2 protein. However the detection of large-scale deletions in the 3' end of the PMS2 gene has not been possible due to technical difficulties associated with pseudogene sequences. Here, we utilised a recently described MLPA/long-range PCR-based approach to screen the remaining 22 % (n = 16) of CRC-affected probands for mutations in the 3' end of the PMS2 gene. No deletions encompassing any or all of exons 12 through 15 were identified; therefore, our results suggest that 3' deletions in PMS2 are not a frequent occurrence in such families.

Background: The effects of low-dose medical radiation on breast cancer risk are uncertain, and few studies have included genetically susceptible women, such as those who carry germline BRCA1 and BRCA2 mutations., Methods: We studied 454 BRCA1 and 273 BRCA2 mutation carriers ages younger than 50 years from three breast cancer family registries in the United States, Canada, and Australia/New Zealand. We estimated breast cancer risk associated with diagnostic chest X-rays by comparing mutation carriers with breast cancer (cases) with those without breast cancer (controls). Exposure to chest X-rays was self-reported. Mammograms were not considered in the analysis., Results: After adjusting for known risk factors for breast cancer, the ORs for a history of diagnostic chest X-rays, excluding those for tuberculosis or pneumonia, were 1.16 [95% confidence interval (CI), 0.64-2.11] for BRCA1 mutations carriers and 1.22 (95% CI, 0.62-2.42) for BRCA2 mutations carriers. The OR was statistically elevated for BRCA2 mutation carriers with three to five diagnostic chest X-rays (P = 0.01) but not for those with six or more chest X-rays. Few women reported chest fluoroscopy for tuberculosis or chest X-rays for pneumonia; the OR estimates were elevated, but not statistically significant, for BRCA1 mutation carriers., Conclusions: Our findings do not support a positive association between diagnostic chest X-rays and breast cancer risk before the ages of 50 years for BRCA1 or BRCA2 mutation carriers., Impact: Given the increasing use of diagnostic imaging involving higher ionizing radiation doses, further studies of genetically predisposed women are warranted., (©2013 AACR.)

Background: Lynch syndrome is caused by germline mismatch repair (MMR) gene mutations. The PREMM(1,2,6) model predicts the likelihood of a MMR gene mutation based on personal and family cancer history., Objective: To compare strategies using PREMM(1,2,6) and tumour testing (microsatellite instability (MSI) and/or immunohistochemistry (IHC) staining) to identify mutation carriers., Design: Data from population-based or clinic-based patients with colorectal cancers enrolled through the Colon Cancer Family Registry were analysed. Evaluation included MSI, IHC and germline mutation analysis for MLH1, MSH2, MSH6 and PMS2. Personal and family cancer histories were used to calculate PREMM(1,2,6) predictions. Discriminative ability to identify carriers from non-carriers using the area under the receiver operating characteristic curve (AUC) was assessed. Predictions were based on logistic regression models for (1) cancer assessment using PREMM(1,2,6), (2) MSI, (3) IHC for loss of any MMR protein expression, (4) MSI+IHC, (5) PREMM(1,2,6)+MSI, (6) PREMM(1,2,6)+IHC, (7) PREMM(1,2,6)+IHC+MSI., Results: Among 1651 subjects, 239 (14%) had mutations (90 MLH1, 125 MSH2, 24 MSH6). PREMM(1,2,6) discriminated well with AUC 0.90 (95% CI 0.88 to 0.92). MSI alone, IHC alone, or MSI+IHC each had lower AUCs: 0.77, 0.82 and 0.82, respectively. The added value of IHC+PREMM(1,2,6) was slightly greater than PREMM(1,2,6)+MSI (AUC 0.94 vs 0.93). Adding MSI to PREMM(1,2,6)+IHC did not improve discrimination., Conclusion: PREMM(1,2,6) and IHC showed excellent performance in distinguishing mutation carriers from non-carriers and performed best when combined. MSI may have a greater role in distinguishing Lynch syndrome from other familial colorectal cancer subtypes among cases with high PREMM(1,2,6) scores where genetic evaluation does not disclose a MMR mutation.

Background: Black men currently comprise a substantial percentage of prisoners in the United States. Drug dependence is common among prison populations, and US prisons are high-risk environments for drug use. Prison drug use exacerbates health problems disproportionately prevalent among Black men and prisoners., Objectives: The goal of this research was to examine predictors of prison drug use among incarcerated Black men., Methods: This study examined drug use within the prison environment in a random sample of 134 Black men incarcerated in maximum-security correctional institution. The Addiction Severity Index (ASI) was used to measure illicit drug use history and the extent to which drug use occurred within the prison environment., Results: Seventy-five percent of the participants reported a history of illicit drug use. Overall, 20% (n 25) of the participants, or 25% of those with a history of drug use, reported using drugs during a time frame consistent with incarceration. Participants with lengthier histories of drug use (OR: 1.1, 95% CI 1.0-1.2) and those who were incarcerated longer (OR: 1.1, 95% CI 1.0-1.2) were more likely to use drugs in prison. Drug use in prison was associated with history of injection drug use and with probation/parole status when arrested., Conclusions: Prisoners are engaging in illicit drug use while incarcerated, suggesting that they could benefit from harm reduction and drug treatment services offered during incarceration., Scientific Significance: Drug treatment programs that address long-standing addictions and coping mechanisms for lengthy prison stays, specifically, would be especially useful for this population.

Context: Lynch syndrome is the most common form of hereditary colorectal cancer (CRC) and is caused by germline mutations in DNA mismatch repair (MMR) genes. Identification of gene carriers currently relies on germline analysis in patients with MMR-deficient tumors, but criteria to select individuals in whom tumor MMR testing should be performed are unclear., Objective: To establish a highly sensitive and efficient strategy for the identification of MMR gene mutation carriers among CRC probands., Design, Setting, and Patients: Pooled-data analysis of 4 large cohorts of newly diagnosed CRC probands recruited between 1994 and 2010 (n = 10,206) from the Colon Cancer Family Registry, the EPICOLON project, the Ohio State University, and the University of Helsinki examining personal, tumor-related, and family characteristics, as well as microsatellite instability, tumor MMR immunostaining, and germline MMR mutational status data., Main Outcome: Performance characteristics of selected strategies (Bethesda guidelines, Jerusalem recommendations, and those derived from a bivariate/multivariate analysis of variables associated with Lynch syndrome) were compared with tumor MMR testing of all CRC patients (universal screening)., Results: Of 10,206 informative, unrelated CRC probands, 312 (3.1%) were MMR gene mutation carriers. In the population-based cohorts (n = 3671 probands), the universal screening approach (sensitivity, 100%; 95% CI, 99.3%-100%; specificity, 93.0%; 95% CI, 92.0%-93.7%; diagnostic yield, 2.2%; 95% CI, 1.7%-2.7%) was superior to the use of Bethesda guidelines (sensitivity, 87.8%; 95% CI, 78.9%-93.2%; specificity, 97.5%; 95% CI, 96.9%-98.0%; diagnostic yield, 2.0%; 95% CI, 1.5%-2.4%; P < .001), Jerusalem recommendations (sensitivity, 85.4%; 95% CI, 77.1%-93.6%; specificity, 96.7%; 95% CI, 96.0%-97.2%; diagnostic yield, 1.9%; 95% CI, 1.4%-2.3%; P < .001), and a selective strategy based on tumor MMR testing of cases with CRC diagnosed at age 70 years or younger and in older patients fulfilling the Bethesda guidelines (sensitivity, 95.1%; 95% CI, 89.8%-99.0%; specificity, 95.5%; 95% CI, 94.7%-96.1%; diagnostic yield, 2.1%; 95% CI, 1.6%-2.6%; P < .001). This selective strategy missed 4.9% of Lynch syndrome cases but resulted in 34.8% fewer cases requiring tumor MMR testing and 28.6% fewer cases undergoing germline mutational analysis than the universal approach., Conclusion: Universal tumor MMR testing among CRC probands had a greater sensitivity for the identification of Lynch syndrome compared with multiple alternative strategies, although the increase in the diagnostic yield was modest.

Purpose: Lynch syndrome accounts for 2-5% of endometrial cancer cases. Lynch syndrome prediction models have not been evaluated among endometrial cancer cases., Methods: Area under the receiver operating curve (AUC), sensitivity and specificity of PREMM(1,2,6), MMRpredict, and MMRpro scores were assessed among 563 population-based and 129 clinic-based endometrial cancer cases., Results: A total of 14 (3%) population-based and 80 (62%) clinic-based subjects had pathogenic mutations. PREMM(1,2,6), MMRpredict, and MMRpro were able to distinguish mutation carriers from noncarriers (AUC of 0.77, 0.76, and 0.77, respectively), among population-based cases. All three models had lower discrimination for the clinic-based cohort, with AUCs of 0.67, 0.64, and 0.54, respectively. Using a 5% cutoff, sensitivity and specificity were as follows: PREMM(1,2,6), 93% and 5% among population-based cases and 99% and 2% among clinic-based cases; MMRpredict, 71% and 64% for the population-based cohort and 91% and 0% for the clinic-based cohort; and MMRpro, 57% and 85% among population-based cases and 95% and 10% among clinic-based cases., Conclusion: Currently available prediction models have limited clinical utility in determining which patients with endometrial cancer should undergo genetic testing for Lynch syndrome. Immunohistochemical analysis and microsatellite instability testing may be the best currently available tools to screen for Lynch syndrome in endometrial cancer patients.

Colorectal cancer (CRC) is a significant cause of mortality and morbidity in the United States, much of which could be prevented through adequate screening. Consensus guidelines recommend that high-risk groups initiate screening earlier with colonoscopy and more frequently than average risk persons. However, a large proportion of high risk individuals do not receive regular colonoscopic screening. The Family Health Promotion Project (FHPP) is a randomized-controlled trial to test the effectiveness of a telephone-based counseling intervention to increase adherence to risk-appropriate colonoscopy screening in high risk individuals. Unaffected members of CRC families from two national cancer family registries were enrolled (n=632) and randomized to receive either a single session telephone counseling intervention using Motivational Interviewing techniques or a minimal mail-out intervention. The primary endpoint, rate of colonoscopy screening, was assessed at 6, 12 and 24 months post-enrollment. In this paper, we describe the research design and telephone counseling intervention of the FHPP trial, and report baseline data obtained from the two high risk cohorts recruited into this trial. Results obtained at baseline confirm the need for interventions to promote colonoscopy screening among these high risk individuals, as well as highlighting several key opportunities for intervention, including increasing knowledge about risk-appropriate screening guidelines, and providing both tailored risk information and barriers counseling., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region., Competing Interests: CB and EGB are on the Scientific Advisory Board of 23andme's project "Roots into the Future." 23andme is a Mountain View, CA, company that provides direct-to-consumer genetic products. CB is also on the SAB of Ancestry.com, a company in Provo, UT, that provides direct-to-consumer genetic products. Neither company played a part in the research described here or has a financial stake in the results. The remaining authors have declared that no competing interests exist.

Objective: To explore levels of perceived racial and non-racial discrimination and their associations with self-esteem and mastery in the U.S.A. and South Africa., Design: We used ordinary least square regressions to test the cross-sectional associations between discrimination and psychological resources using two national probability samples of adults: the National Survey of American Life and the South African Stress and Health Study., Results: Levels of perceived racial discrimination were higher in the U.S.A. than in South Africa. In the U.S.A., both African-Americans and Caribbean blacks have comparable or higher levels of self-esteem and mastery than whites. In contrast, South African whites have higher levels of both self-esteem and mastery than Africans, Coloureds, and Indians. Perceived discrimination, especially chronic everyday discrimination, is inversely related to self-esteem and mastery in both societies. In South Africa, stress and socioeconomic status (SES) but not discrimination are important determinants of racial differences in self-esteem and mastery., Conclusions: In two racialized societies, perceived discrimination acts independent of demographic factors, general stressors, social desirability bias, racial identity, and SES, to negatively affect the psychological resources of self-esteem and mastery.

Stigma and social inequality deprive disadvantaged social groups of a sense of social well-being. Stress researchers have focused on prejudice-related events and conditions but have not described more intangible stressors experienced by sexual minorities. We use narrative methods to examine how sexual minorities experience stigma and social inequality as we focus on the more intangible stressors that are both pervasive and difficult to measure. Three themes emerged in the narratives of our ethnically diverse sample of 57 adult sexual minority women and men: (a) stigma deprived them of access to critical possibilities and opportunities; (b) stigma deprives them of safety and acceptance; and (c) despite this, the experience of stigma is also related to the adoption of a positive and collective orientation towards their stigmatized identities. Recognizing these stressors and related resilience can direct policy makers toward interventions that go even beyond eliminating prejudice by including goals to strengthen minority communities.