Racial and socioeconomic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy.

PURPOSE: The purpose of this study was to assess the association between race/ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy. METHODS: We analyzed data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015 who received systemic therapy. Race/ethnicity was categorized as Non-Hispanic (NH) White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other. Income and education were combined to form a composite measure of socioeconomic status (SES) and categorized into low-, mid-, and high-SES. Multivariable Cox proportional hazards models were used to assess whether race/ethnicity was associated with the risk of death after adjusting for sociodemographic, clinical, and treatment factors. Additionally, subgroup analyses were conducted by SES, age, and surgery receipt. RESULTS: The study population comprised 53,367 women (52.4% ages ≥ 65 years, 82% NH-White, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) in the analysis. After adjusting for covariates, the NH-Black race was associated with a higher risk of death versus NH-White race (aHR: 1.12; 95% CI: 1.07,1.18), while Hispanic ethnicity was associated with a lower risk of death compared to NH-White women (aHR: 0.87; 95% CI: 0.80, 0.95). Furthermore, NH-Black women versus NH-White women had an increased risk of mortality among those with low-SES characteristics (aHR:1.12; 95% CI:1.03-1.22) and mid-SES groups (aHR: 1.13; 95% CI:1.05-1.21). CONCLUSIONS: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced poorer survival compared to NH-White women. Future studies should be directed to identify drivers of ovarian cancer disparities, particularly racial differences in treatment response and surveillance.

Persistent poverty disparities in incidence and outcomes among oral and pharynx cancer patients.

PURPOSE: Disparities in oral cavity and pharyngeal cancer based on race/ethnicity and socioeconomic status have been reported, but the impact of living within areas that are persistently poor at the time of diagnosis and outcome is unknown. This study aimed to investigate whether the incidence, 5-year relative survival, stage at diagnosis, and mortality among patients with oral cavity and pharyngeal cancers varied by persistent poverty. METHODS: Data were drawn from the SEER database (2006-2017) and included individuals diagnosed with oral cavity and pharyngeal cancers. Persistent poverty (at census tract) is defined as areas where ≥ 20% of the population has lived below the poverty level for ~ 30 years. Age-adjusted incidence and 5-year survival rates were calculated. Multivariable logistic regression was used to estimate the association between persistent poverty and advanced stage cancer. Cumulative incidence and multivariable subdistribution hazard models were used to evaluate mortality risk. In addition, results were stratified by cancer primary site, sex, race/ethnicity, and rurality. RESULTS: Of the 90,631 patients included in the analysis (61.7% < 65 years old, 71.6% males), 8.8% lived in persistent poverty. Compared to non-persistent poverty, patients in persistent poverty had higher incidence and lower 5-year survival rates. Throughout 10 years, the cumulative incidence of cancer death was greater in patients from persistent poverty and were more likely to present with advanced-stage cancer and higher mortality risk. In the stratified analysis by primary site, patients in persistent poverty with oropharyngeal, oral cavity, and nasopharyngeal cancers had an increased risk of mortality compared to the patients in non-persistent poverty. CONCLUSION: This study found an association between oral cavity and pharyngeal cancer outcomes among patients in persistent poverty indicating a multidimensional strategy to improve survival.

Association of Physical Frailty and Cognitive Function in a Population-Based Cross-Sectional Study of American Older Adults.

INTRODUCTION: Cognitive impairment and frailty are prevalent in older persons. Physical frailty is associated with cognitive decline; however, the role of effect modifiers such as age, sex, race/ethnicity, and cognitive reserve is not well understood. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (2011-2014) were obtained for participants aged ≥60 years. Complete availability of cognitive scores was an inclusion criterion. Physical frailty was defined by the presence of exhaustion, weakness, low body mass, and/or low physical activity, and categorized into three groups: robust (0 present), pre-frail (1-2 present), or frail (3-4 present). Four cognitive test scores were converted to z-scores, and global cognition (composite z-score) was calculated by averaging the four-individual z-scores. Multivariable linear regression models were fit to estimate the associations between frailty and cognitive function. Frailty was also evaluated as a risk factor for self-reported subjective memory complaint (SMC) using logistic regression. All models were adjusted for age, sex, race/ethnicity, education, alcohol use, income, marital status, diabetes, hypertension, and history of stroke. Effect measure modification analyses were conducted by age, sex, race/ethnicity, education, and occupational cognitive demand. RESULTS: The study population comprised 2,863 participants aged ≥60 years. 50.6% of the participants were categorized into robust, 43.2% pre-frail, and 6.2% frail. After adjusting for covariates, compared to robust participants, frail and prefrail participants had lower adjusted mean global cognitive z-scores, ß^ = -0.61, 95% CI: -0.83, -0.38 and ß^ = -0.21, 95% CI: -0.30, -0.12, respectively. Both prefrail and frail participants had higher odds of SMC compared to the robust participants. We did not see strong evidence that the association between frailty and cognition was modified by the factors we studied. DISCUSSION/CONCLUSION: Both pre-frailty and frailty were associated with lower cognitive performance and were more likely to report subjective memory complaints relative to persons without frailty. These findings provide additional evidence that physical frailty may serve as a prognostic factor for cognitive deterioration or dementia, and prevention of frailty may be an important public health strategy.

Association of air pollution with postmenopausal breast cancer risk in UK Biobank.

BACKGROUND: We investigated the association of several air pollution measures with postmenopausal breast cancer (BCa) risk. METHODS: This study included 155,235 postmenopausal women (of which 6146 with BCa) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Annual exposure averages were available from 2005, 2006, 2007, and 2010 for NO2, from 2007 and 2010 for PM10, and from 2010 for PM2.5, NOX, PM2.5-10 and PM2.5 absorbance. Information on BCa risk factors was collected at baseline. Cox proportional hazards regression was used to evaluate the associations of year-specific and cumulative average exposures with BCa risk, overall and with 2-year exposure lag, while adjusting for BCa risk factors. RESULTS: PM10 in 2007 and cumulative average PM10 were positively associated with BCa risk (2007 PM10: Hazard ratio [HR] per 10 µg/m3 = 1.18, 95% CI 1.08, 1.29; cumulative average PM10: HR per 10 µg/m3 = 1.99, 95% CI 1.75, 2.27). Compared to women with low exposure, women with higher 2007 PM10 and cumulative average PM10 had greater BCa risk (4th vs. 1st quartile HR = 1.15, 95% CI 1.07, 1.24, p-trend = 0.001 and HR = 1.35, 95% CI 1.25, 1.44, p-trend < 0.0001, respectively). No significant associations were found for any other exposure measures. In the analysis with 2-year exposure lag, both 2007 PM 10 and cumulative average PM10 were positively associated with BCa risk (4th vs. 1st quartile HR = 1.19, 95% CI 1.10, 1.28 and HR = 1.29, 95% CI 1.19, 1.39, respectively). CONCLUSION: Our findings suggest a positive association of 2007 PM10 and cumulative average PM10 with postmenopausal BCa risk.

Trends and factors associated with secondhand smoke exposure among US cancer survivors, 2013-2020.

BACKGROUND: Secondhand smoke (SHS) poses a significant public health threat. Cancer survivors are at a greater risk of adverse health outcomes from SHS because of its association with poor prognosis and other downstream clinical events. METHODS: A nationally representative sample of US adults aged 20 years and older was analyzed from the National Health and Nutrition Examination Survey between 2013 and 2020. Data on indoor SHS exposure were reported by 16,778 adults who were not currently smoking (1775 cancer survivors; 15,003 individuals without a cancer history). The weighted prevalence of SHS exposure was estimated and compared across sociodemographic and health-related characteristics. Multivariable logistic regression models were fitted to identify correlates of SHS exposure. RESULTS: Of the 1775 nonsmoking cancer survivors (mean age, 64.9 years; 57.0% female; 84.4% non-Hispanic Whites), 15.8% reported SHS exposure. No significant change in trends of SHS exposure was observed during the study period. The prevalence of SHS exposure was higher in cancer survivors who were younger, racial minorities, and had a household income below 130% of the federal poverty level. After adjustment for multiple correlates, age below 40 years, low income, smoking history, and diagnosis within 2 years were associated with SHS exposure. Cancer survivors were most likely to report that SHS exposure occurred at home or in a car. CONCLUSIONS: The prevalence of SHS exposure among cancer survivors remained steady in the past decade. However, disparities exist in SHS exposure among cancer survivors across sociodemographic characteristics and smoking status. Smoking cessation programs should be promoted among caregivers and families of cancer survivors.

Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer's-type neuropathology.

Cancer and Alzheimer's disease are common diseases in ageing populations. Previous research has reported a lower incidence of Alzheimer's disease-type (amnestic) dementia among individuals with a diagnosis of cancer. Both cancer and amnestic dementia are prevalent and potentially lethal clinical syndromes. The current study was conducted to investigate the association of cancer diagnosis with neuropathological and cognitive features of dementia. Data were analysed from longitudinally evaluated participants in a community-based cohort study of brain ageing who came to autopsy at the University of Kentucky Alzheimer's Disease Research Center. These data were linked to the Kentucky Cancer Registry, a population-based state cancer surveillance system, to obtain cancer-related data. We examined the relationship between cancer diagnosis, clinical dementia diagnosis, Mini-Mental State Examination scores and neuropathological features using inverse probability weighting to address bias due to confounding and missing data. To address bias due to inclusion of participants with dementia at cohort baseline, we repeated all analyses restricted to the participants who were cognitively normal at baseline. Included participants (n = 785) had a mean ± standard deviation age of death of 83.8 ± 8.6 years; 60.1% were female. Cancer diagnosis was determined in 190 (24.2%) participants, and a diagnosis of mild cognitive impairment or dementia was determined in 539 (68.7%). APOE ɛ4 allele dosage was lower among participants with cancer diagnosis compared to cancer-free participants overall (P = 0.0072); however, this association was not observed among those who were cognitively normal at baseline. Participants with cancer diagnosis had lower odds of mild cognitive impairment or dementia, and higher cognitive test scores (e.g. Mini-Mental State Examination scores evaluated 6 and ≤2 years ante-mortem, P < 0.001 for both comparisons). Cancer diagnosis also associated with lower odds of higher Braak neurofibrillary tangle stages (III/IV) or (V/VI), moderate/frequent neuritic plaques, moderate/frequent diffuse plaques and moderate/severe cerebral amyloid angiopathy (all P < 0.05). By contrast, TDP-43, α-synuclein and cerebrovascular pathologies were not associated with cancer diagnosis. Cancer diagnosis was associated with a lower burden of Alzheimer's disease pathology and less cognitive impairment. These findings from a community-based cohort with neuropathological confirmation of substrates support the hypothesis that there is an inverse relationship between cancer and Alzheimer's disease.

Cost-Effectiveness of Screening Mammography Beyond Age 75 Years : A Cost-Effectiveness Analysis.

BACKGROUND: The cost-effectiveness of screening mammography beyond age 75 years remains unclear. OBJECTIVE: To estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden. DESIGN: Markov microsimulation model. DATA SOURCES: SEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium. TARGET POPULATION: U.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS). TIME HORIZON: Lifetime. PERSPECTIVE: National health payer. INTERVENTION: Screening mammography to age 75, 80, 85, or 90 years. OUTCOME MEASURES: Breast cancer death, survival, and costs. RESULTS OF BASE-CASE ANALYSIS: Extending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer. RESULTS OF SENSITIVITY ANALYSIS: Costs per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography. LIMITATION: No randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs. CONCLUSION: Although annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer. PRIMARY FUNDING SOURCE: National Cancer Institute and National Institutes of Health.

Frailty and risk of mortality in older cancer survivors and adults without a cancer history: Evidence from the National Health and Nutrition Examination Survey, 1999-2014.

BACKGROUND: Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited. METHODS: A total of 2050 older adults (≥60 years old) surviving for at least 1 year after a cancer diagnosis and 9474 older adults without a cancer history from the National Health and Nutrition Examination Survey (1999-2014) were included for analysis. The exposure variable, a 45-item frailty index (FI), was categorized on the basis of validated cutoffs (FI ≤ 0.10 [fit], 0.10 < FI ≤ 0.21 [prefrail], and FI > 0.21 [frail]). All-cause mortality was ascertained via the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for the FI, and this was followed by restricted cubic splines depicting dose-response curves. RESULTS: For older cancer survivors, the mean age at the baseline was 72.6 years (SD, 7.1 years); 5.9% were fit, 38.2% were prefrail, and 55.9% were frail. Older adults without a cancer history were slightly younger (mean age, 70.0 years) and less frail (47.9% were frail). At each level of the FI, cancer survivors (1.9 per 100 person-years for FI ≤ 0.10, 3.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 7.5 per 100 person-years for FI > 0.21) had higher mortality than their cancer-free counterparts (1.4 per 100 person-years for FI ≤ 0.10, 2.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 5.4 per 100 person-years for FI > 0.21). The multivariable model suggested a positive association between the FI and all-cause mortality for survivors (aHR for FI > 0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73-4.53) and participants without a cancer history (aHR for FI > 0.21 vs FI ≤ 0.10, 2.75; 95% CI, 2.29-3.32). Restricted cubic splines indicated that all-cause mortality risk increased with the FI in a monotonic pattern. CONCLUSIONS: Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history.

Mammography adherence in relation to function-related indicators in older women.

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations.

Patterns of de-novo metastasis and breast cancer-specific mortality by race and molecular subtype in the SEER population-based dataset.

PURPOSE: To examine patterns of de-novo metastases (mets) and association with breast cancer-specific mortality across subtypes and racial groups. METHODS: Non-Hispanic (NH) Black and NH-White patients ages 40 years and older with primary breast cancer (BC) between 2010 and 2015 were examined. Multilevel logistic regression and Cox proportional hazards models were used to assess (1) odds of de-novo mets to specific sites by subtype, and (2) association of subtype with risk of BC mortality among patients with de-novo mets by race. RESULTS: A total of 204,941 BC patients were included in analysis. The most common de-novo mets site was to the bone, and overall prevalence of de-novo mets was higher among NH-Black (6.4%) versus NH-White (4.1%) patients. The odds of de-novo mets to any site were lower for TNBC (OR 0.68, 95% CI 0.62-0.73) and HR+/HER2- (OR 0.50, 95% CI 0.47-0.53) subtypes, but higher for HR-/HER2+ (OR 1.16, 95% CI 1.06-1.28) relative to HR+/HER2+ . De-novo mets to the brain only was associated with the highest mortality risk across all subtypes, ranging from a 13-fold increase (hazard ratio 13.45, 95% CI 5.03-35.96) for HR-/HER2+ to a 39-fold increase (hazard ratio 39.04, 95% CI 26.2-58.14) for HR+/HER2-. CONCLUSION: Site and fatality of de-novo mets vary by subtype and by race. This information may help improve risk stratification and post-diagnostic surveillance to ultimately reduce BC mortality.

The association between cognitive impairment and breast and colorectal cancer screening utilization.

BACKGROUND: Undergoing cancer screening is a debatable topic in patients with cognitive impairment. In this study, we aimed to examine the utilization and predictors of breast and colorectal cancer screening among screening eligible, cognitively impaired individuals. METHODS: We analyzed the 2018 and 2019 National Health Interview Survey data (n = 12,965 and 24,782, respectively) on individuals eligible for breast or colorectal cancer screening. We calculated the percentage of cancer screening eligible individuals who received mammogram or colonoscopy by cognitive impairment status. We used multivariable logistic regression to examine whether having a recent mammogram or colonoscopy differed by cognitive impairment status, adjusting for covariates. RESULTS: We observed a significantly lower percentage of mammogram use in the screening eligible, cognitively impaired (mild or severe) versus unimpaired women. Adjusting for the covariates, the cognitively impaired women, mild (odds ratio [OR] = 0.85; p = 0.015) or severe (OR = 0.54; p <  0.001), were less likely to have had a recent mammogram compared to the cognitively unimpaired women. Although statistically non-significant, the percentage of colonoscopy use in the screening eligible, cognitively impaired individuals were slightly higher than that in the cognitively unimpaired individuals. In the regression analysis, we found the cognitively impaired men, mild (OR = 0.79; p <  0.001) or severe (OR = 0.69; p = 0.038), were less likely to have had a recent colonoscopy compared to the cognitively unimpaired men. More studies are needed to examine the multilevel factors that underpin the difference in cancer screening utilization in this vulnerable population. CONCLUSION: Our results highlight the need for additional research to address utilization and effectiveness of cancer screening in individuals with cognitive impairment.

Self-rated health in relation to fruit and vegetable consumption and physical activity among older cancer survivors.

PURPOSE: We aimed to investigate associations of self-rated health with fruit and vegetable consumption (FVC) and physical activity (PA) among older cancer survivors. METHODS: We used the 2017 Behavioral Risk Factor Surveillance System to identify cancer survivors ≥ 65 years (N = 2663). Self-reported FVC and PA were categorized as ordinal variables to approximate quartiles. Low general health (LGH) was defined as fair or poor self-rated health. A multivariable logistic regression treating LGH as the outcome was used to calculate adjusted odd ratios (aORs) and 95% confidence intervals (CIs) for FVC and PA. Restricted cubic spline depicted non-linear dose-response curves for FVC and PA. In comparative analysis, we used the same logistic regression and dose-response model to calculate ORs of FVC and PA in 73,134 people ≥ 65 years without cancer history. RESULTS: Overall, 470 (17.7%) survivors had LGH. Survivors' mean age was 73.3 years (SD = 5.2), 55.1% of them were female, and 95.4% self-reported as white. In cancer survivors, FVC was not associated with LGH (≥ 28 vs. < 14 times/week: aOR = 1.02, 95% CI = 0.75-1.39, p-trend = 0.50), whereas PA was inversely associated with LGH (≥ 30 vs. < 7 MET-hours/week: aOR = 0.55, 95% CI = 0.41-0.75, p-trend < 0.01). Dose-response curves demonstrated consistent association patterns. In comparative analysis, ORs of PA did not change substantially but we observed inverse association for FVC. CONCLUSIONS: An inverse association between PA and LGH was observed among older cancer survivors, but no significant association was obtained for FVC among them. Regular PA may maintain or indicate a favorable health in older cancer survivors, whereas impacts of FVC deserve further investigations.

Metabolic syndrome and risk of breast cancer mortality by menopause, obesity, and subtype.

PURPOSE: To investigate the association between metabolic syndrome (MetS) and risk of breast cancer mortality by menopausal status, obesity, and subtype. METHODS: Data from 94,555 women free of cancer at baseline in the National Institute of Health-American Association of Retired Persons Diet and Health Study cohort (NIH-AARP) were used to investigate the prospective associations of baseline MetS and components with risk of breast cancer mortality using Cox proportional hazard regression models adjusted for baseline behavioral and demographic covariates. RESULTS: During a mean follow-up duration of 14 years, 607 women in the cohort died of breast cancer. Overall, MetS was associated with a 73% increased risk of breast cancer mortality (HR 1.73; 95% CI 1.09-2.75); the association remained significant among post-menopausal women overall (HR 2.07, 95% CI 1.32, 3.25), and among those with overweight/obesity (HR 1.15, 95% CI 0.81, 1.64). MetS was associated with increased risk of breast cancer mortality for ER+/PR+ (HR 1.28, 95% CI 0.52, 3.16) and lower risk for ER-/PR- (HR 0.44, 95% CI 0.11, 1.75) subtypes; however, the associations were not statistically significant. Of the individual MetS components, high waist circumference (HR 1.32, 95% CI 1.03, 1.70), high cholesterol (HR 1.24, 95% CI 1.05, 1.46), and hypertension (HR 1.24, 95% CI 1.05, 1.46) were independently associated with increased risk of breast cancer mortality. CONCLUSIONS: MetS was associated with increased risk of breast cancer mortality, especially among post-menopausal women. Further studies with larger sample sizes are needed to definitively determine the extent to which these associations vary by breast cancer subtype.

Socioeconomic gradients in cancer incidence by race and ethnicity in California, 2008-2012: the influence of tobacco use or screening detectable cancers.

PURPOSE: There are clearly documented inequalities in cancer incidence by socioeconomic position, but it is unclear whether this is due primarily to differences in tobacco exposure and screening practices or to other factors. METHODS: Our study included 741,373 incident cases of invasive cancer from 2008 to 2012 in California. We calculated age-standardized incidence rates across twelve categories of census tract poverty as a measure of socioeconomic position (SEP) for (1) all cancer sites combined, (2) sites not strongly related to tobacco use, (3) sites not related to screening, and (4) sites not related to tobacco use or screening. RESULTS: There was higher cancer incidence among those living in areas with higher levels of poverty for sites not strongly related to tobacco use or screening, among Whites, Blacks, and Asians, but not among Latinos. Among Whites there was no relationship with census tract poverty at lower levels of poverty-the relationship with cancer incidence was primarily among those in higher poverty. For Blacks and Asians, there is a more linear relationship with cancer incidence across levels of poverty. CONCLUSIONS: SEP gradients in cancer incidence remain after exclusion of cancer sites strongly related to tobacco use and screening. Our findings demonstrate a need for research on other environmental and social causes of cancer where exposures are differentially distributed by SEP.

Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.

BACKGROUND: CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis. METHODS: We searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques. RESULTS: The pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21-24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries. CONCLUSION: Although no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

Incorporating Coexisting Chronic Illness into Decisions about Patient Selection for Lung Cancer Screening. An Official American Thoracic Society Research Statement.

BACKGROUND: Lung cancer screening (LCS) has the potential to reduce the risk of lung cancer death in healthy individuals, but the impact of coexisting chronic illnesses on LCS outcomes has not been well defined. Consideration of the complex relationship between baseline risk of lung cancer, treatment-related harms, and risk of death from competing causes is crucial in determining the balance of benefits and harms of LCS. OBJECTIVES: To summarize evidence, identify knowledge and research gaps, prioritize topics, and propose methods for future research on how best to incorporate comorbidities in making decisions regarding LCS. METHODS: A multidisciplinary group of international clinicians and researchers reviewed available data on the effects of comorbidities on LCS outcomes, focusing on the juxtaposition of lung cancer risk and competing risks of death, consideration of benefits and risks in patients with chronic obstructive pulmonary disease, communication of risk, and treatment of screen-detected lung cancer. RESULTS: This statement identifies gaps in knowledge regarding how comorbidities and competing causes of death impact outcomes in LCS, and we have developed questions to help guide future research efforts to better inform patient selection, education, and implementation of LCS. CONCLUSIONS: There is an urgent need for further research that can help guide clinical decision-making with patients who may not benefit from LCS owing to coexisting chronic illness. This statement establishes a research framework to address essential questions regarding how to incorporate and communicate risks of comorbidities into patient selection and decisions regarding LCS.

Lifecourse socioeconomic status and cancer-related risk factors: Analysis of the WHO study on global ageing and adult health (SAGE).

Few studies have examined cancer-related risk factors in relation to SES across the lifecourse in low to middle income countries. This analysis focuses on adult women in India, China, Mexico, Russia and South Africa, and examines the association between individual, parental and lifecourse SES with smoking, alcohol, BMI, nutrition and physical activity. Data on 22,283 women aged 18 years and older were obtained from the 2007 WHO Study on Global Aging and Adult Health (SAGE). Overall, 34% of women had no formal education, 73% had mothers with no formal education and 73% of women had low lifecourse SES. Low SES women were almost four times more likely to exceed alcohol use guidelines (OR: 3.86, 95% CI: 1.23-12.10), and 68% more likely to smoke (OR: 1.68, 95% CI: 1.01-2.80) compared with higher SES. Women with low SES mothers and fathers were more likely to have poor nutrition (Mothers OR: 1.59, 95% CI: 1.17-2.16; Fathers OR: 1.33, 95% CI: 1.11-1.59) and more likely to smoke (Mothers OR: 1.46, 95% CI: 1.15-1.87; Fathers OR: 2.17, 95% CI: 1.80-2.63) compared with those with high SES parents. Women with stable low lifecourse SES were more likely to smoke (OR: 2.55, 95% CI: 1.47-4.43), while those with declining lifecourse SES were more likely to exceed alcohol use guidelines (OR: 3.63, 95% CI: 1.07-12.34). Cancer-related risk factors varied significantly by lifecourse SES, suggesting that cancer prevention strategies will need to be tailored to specific sub-groups in order to be most effective.

Chronic inflammation and risk of colorectal and other obesity-related cancers: The health, aging and body composition study.

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults.

Mortality risk from comorbidities independent of triple-negative breast cancer status: NCI-SEER-based cohort analysis.

PURPOSE: A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients. METHODS: We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. RESULTS: Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90-11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68-5.29). CONCLUSIONS: comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.