Smoking Inequality Trends by Disability and Income in Australia, 2001 to 2020.

BACKGROUND: While policies to reduce smoking in many countries have been successful, disadvantaged groups (such as low-income groups) have only seen minor gains. People with disability are one such disadvantaged group and are more likely to smoke. However, evidence is limited on trends and inequalities in smoking for disabled people and on whether those also on low incomes are more likely to smoke. METHODS: We use annual data from 2001 to 2020 of the Household Income and Labour Dynamics in Australia survey. We use a Bayesian model to estimate smoking prevalence trends and inequalities for people with disability (2020, n = 1,370) and without disability (2020, n = 6,229) across the whole population and within income tertiles. To avoid reverse causation (smoking causing disability), we focus on younger people (15-44 years). RESULTS: Absolute reductions (per 100 people, [95% credible intervals]) in smoking were similar for people with (-13 [-16, -11]) and without disability (-15 [-16, -14]), with stable absolute but increasing relative inequalities. In the low-income group, absolute reductions in smoking prevalence for people with disability (-10 [-14, -6]) were smaller than in people without disability (-14 [-15, -12]), resulting in moderate evidence for increasing absolute inequalities (4 [0, 8]) and strong evidence for increasing relative inequalities. In high-income groups, disability-related absolute inequalities narrowed (-6 [-10, -3]), and relative inequalities were stable. CONCLUSIONS: Disabled people in Australia, especially those on low incomes, show signs of being left behind in efforts to reduce smoking.

Hierarchical Models for International Comparisons: Smoking, Disability, and Social Inequality in 21 European Countries.

BACKGROUND: International comparisons of social inequalities in health outcomes and behaviors are challenging. Due to the level of disaggregation often required, data can be sparse and methods to make adequately powered comparisons are lacking. We aimed to illustrate the value of a hierarchical Bayesian approach that partially pools country-level estimates, reducing the influence of sampling variation and increasing the stability of estimates. We also illustrate a new way of simultaneously displaying the uncertainty of both relative and absolute inequality estimates. METHODS: We used the 2014 European Social Survey to estimate smoking prevalence, absolute, and relative inequalities for men and women with and without disabilities in 21 European countries. We simultaneously display smoking prevalence for people without disabilities (x-axis), absolute (y-axis), and relative inequalities (contour lines), capturing the uncertainty of these estimates by plotting a 2-D normal approximation of the posterior distribution from the full probability (Bayesian) analysis. RESULTS: Our study confirms that across Europe smoking prevalence is generally higher for people with disabilities than for those without. Our model shifts more extreme prevalence estimates that are based on fewer observations, toward the European mean. CONCLUSIONS: We demonstrate the utility of partial pooling to make adequately powered estimates of inequality, allowing estimates from countries with smaller sample sizes to benefit from the increased precision of the European average. Including uncertainty on our inequality plot provides a useful tool for evaluating both the geographical patterns of variation in, and strength of evidence for, differences in social inequalities in health.

Does a modifiable risk factor score predict disability worsening in people with multiple sclerosis?

BACKGROUND: Risk factors for chronic disease include smoking, hazardous alcohol consumption, physical inactivity, unhealthy body mass index and poor diet (SNAP factors). In multiple sclerosis (MS) SNAP factors are associated with health outcomes such as disability in cross-sectional studies, but longitudinal data are lacking. OBJECTIVE: The objective of this study was to assess whether a combined SNAP risk score predicts disability worsening. METHODS: Longitudinal self-reported data from two time-points 2.5 years apart from an international survey of 1225 people with MS were used in linear regression models adjusted for potential confounding. Disability worsening was measured using the patient-derived Multiple Sclerosis Severity Score. RESULTS: The majority (62%) had two or more risk factors, with insufficient fruit and vegetable intake (83%), unhealthy body mass index (42%) and physical inactivity (33%) most common. Some SNAP factors at follow-up were associated with disability at follow-up (cross-sectionally), and in addition there was some evidence that increasing risk factors was associated with disability worsening over the 2.5 year study period. Baseline SNAP score was not predictive of disability worsening at follow-up, however. CONCLUSION: Known risk factors for morbidity and mortality were common and associated with disability cross-sectionally, but not prospectively. Further studies using longer time frames, objective measures and interventions may elucidate potential benefits from changes in risk factors on MS outcomes.

Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2.

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.

MicroRNA related polymorphisms and breast cancer risk.

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

Introduction to causal diagrams for confounder selection.

In respiratory health research, interest often lies in estimating the effect of an exposure on a health outcome. If randomization of the exposure of interest is not possible, estimating its effect is typically complicated by confounding bias. This can often be dealt with by controlling for the variables causing the confounding, if measured, in the statistical analysis. Common statistical methods used to achieve this include multivariable regression models adjusting for selected confounding variables or stratification on those variables. Therefore, a key question is which measured variables need to be controlled for in order to remove confounding. An approach to confounder-selection based on the use of causal diagrams (often called directed acyclic graphs) is discussed. A causal diagram is a visual representation of the causal relationships believed to exist between the variables of interest, including the exposure, outcome and potential confounding variables. After creating a causal diagram for the research question, an intuitive and easy-to-use set of rules can be applied, based on a foundation of rigorous mathematics, to decide which measured variables must be controlled for in the statistical analysis in order to remove confounding, to the extent that is possible using the available data. This approach is illustrated by constructing a causal diagram for the research question: 'Does personal smoking affect the risk of subsequent asthma?'. Using data taken from the Tasmanian Longitudinal Health Study, the statistical analysis suggested by the causal diagram approach was performed.

AutoDensity: an automated method to measure mammographic breast density that predicts breast cancer risk and screening outcomes.

INTRODUCTION: While Cumulus - a semi-automated method for measuring breast density - is utilised extensively in research, it is labour-intensive and unsuitable for screening programmes that require an efficient and valid measure on which to base screening recommendations. We develop an automated method to measure breast density (AutoDensity) and compare it to Cumulus in terms of association with breast cancer risk and breast cancer screening outcomes. METHODS: AutoDensity automatically identifies the breast area in the mammogram and classifies breast density in a similar way to Cumulus, through a fast, stand-alone Windows or Linux program. Our sample comprised 985 women with screen-detected cancers, 367 women with interval cancers and 4,975 controls (women who did not have cancer), sampled from first and subsequent screening rounds of a film mammography screening programme. To test the validity of AutoDensity, we compared the effect estimates using AutoDensity with those using Cumulus from logistic regression models that tested the association between breast density and breast cancer risk, risk of small and large screen-detected cancers and interval cancers, and screening programme sensitivity (the proportion of cancers that are screen-detected). As a secondary analysis, we report on correlation between AutoDensity and Cumulus measures. RESULTS: AutoDensity performed similarly to Cumulus in all associations tested. For example, using AutoDensity, the odds ratios for women in the highest decile of breast density compared to women in the lowest quintile for invasive breast cancer, interval cancers, large and small screen-detected cancers were 3.2 (95% CI 2.5 to 4.1), 4.7 (95% CI 3.0 to 7.4), 6.4 (95% CI 3.7 to 11.1) and 2.2 (95% CI 1.6 to 3.0) respectively. For Cumulus the corresponding odds ratios were: 2.4 (95% CI 1.9 to 3.1), 4.1 (95% CI 2.6 to 6.3), 6.6 (95% CI 3.7 to 11.7) and 1.3 (95% CI 0.9 to 1.8). Correlation between Cumulus and AutoDensity measures was 0.63 (P < 0.001). CONCLUSIONS: Based on the similarity of the effect estimates for AutoDensity and Cumulus inmodels of breast density and breast cancer risk and screening outcomes, we conclude that AutoDensity is a valid automated method for measuring breast density from digitised film mammograms.

Mammographic density and markers of socioeconomic status: a cross-sectional study.

BACKGROUND: Socioeconomic status (SES) is known to be positively associated with breast cancer risk but its relationship with mammographic density, a marker of susceptibility to breast cancer, is unclear. This study aims to investigate whether mammographic density varies by SES and to identify the underlying anthropometric, lifestyle and reproductive factors leading to such variation. METHODS: In a cross-sectional study of mammographic density in 487 pre-menopausal women, SES was assessed from questionnaire data using highest achieved level of formal education, quintiles of Census-derived Townsend scores and urban/rural classification of place of residence. Mammographic density was measured on digitised films using a computer-assisted method. Linear regression models were fitted to assess the association between SES variables and mammographic density, adjusting for correlated variables. RESULTS: In unadjusted models, percent density was positively associated with SES, with an absolute difference in percent density of 6.3% (95% CI 1.6%, 10.5%) between highest and lowest educational categories, and of 6.6% (95% CI -0.7%, 12.9%) between highest and lowest Townsend quintiles. These associations were mainly driven by strong negative associations between these SES variables and lucent area and were attenuated upon adjustment for body mass index (BMI). There was little evidence that reproductive factors explained this association. SES was not associated with the amount of dense tissue in the breast before or after BMI adjustment. The effect of education on percent density persisted after adjustment for Townsend score. Mammographic measures did not vary according to urban/rural place of residence. CONCLUSIONS: The observed SES gradients in percent density paralleled known SES gradients in breast cancer risk. Although consistent with the hypothesis that percent density may be a mediator of the SES differentials in breast cancer risk, the SES gradients in percent density were mainly driven by the negative association between SES and BMI. Nevertheless, as density affects the sensitivity of screen-film mammography, the higher percent density found among high SES women would imply that these women have a higher risk of developing cancer but a lower likelihood of having it detected earlier.

Screen-film mammographic density and breast cancer risk: a comparison of the volumetric standard mammogram form and the interactive threshold measurement methods.

BACKGROUND: Mammographic density is a strong risk factor for breast cancer, usually measured by an area-based threshold method that dichotomizes the breast area on a mammogram into dense and nondense regions. Volumetric methods of breast density measurement, such as the fully automated standard mammogram form (SMF) method that estimates the volume of dense and total breast tissue, may provide a more accurate density measurement and improve risk prediction. METHODS: In 2000-2003, a case-control study was conducted of 367 newly confirmed breast cancer cases and 661 age-matched breast cancer-free controls who underwent screen-film mammography at several centers in Toronto, Canada. Conditional logistic regression was used to estimate odds ratios of breast cancer associated with categories of mammographic density, measured with both the threshold and the SMF (version 2.2beta) methods, adjusting for breast cancer risk factors. RESULTS: Median percent density was higher in cases than in controls for the threshold method (31% versus 27%) but not for the SMF method. Higher correlations were observed between SMF and threshold measurements for breast volume/area (Spearman correlation coefficient = 0.95) than for percent density (0.68) or for absolute density (0.36). After adjustment for breast cancer risk factors, odds ratios of breast cancer in the highest compared with the lowest quintile of percent density were 2.19 (95% confidence interval, 1.28-3.72; P(t) <0.01) for the threshold method and 1.27 (95% confidence interval, 0.79-2.04; Pt = 0.32) for the SMF method. CONCLUSION: Threshold percent density is a stronger predictor of breast cancer risk than the SMF version 2.2beta method in digitized images.