The Development and Validation of a Psychometric Tool to Assess Behavioral Factors Impacting Personal Dosimeter Use among Medical Radiation Workers.

ABSTRACT: Personal dosimeters are used by medical radiation workers (MRWs) to monitor their radiation dose from external sources and comply with radiation safety guidelines. Nevertheless, there is evidence of inconsistent use of the devices among MRWs. Behavioral factors influencing the use of personal dosimeters have never been explored. Using established behavioral models, we aimed to develop a psychometric tool to measure the behavioral factors influencing dosimeter use and establish its feasibility, reliability, and validity. A 37-item tool was developed based on a qualitative study and review of the literature. The content relevancy was assessed by six field experts before it was piloted and re-tested on MRWs. The construct validity of the tool was analyzed using exploratory factor analysis to confirm its psychometric properties. Face validation was performed by academicians, field experts, and MRWs to enhance the tool's readability. The 37 items in the tool belonged to five constructs in the early phase. However, the validation study revealed a reliable 27 item tool with seven constructs, namely: "Attitude," "Social factors," "Ability to perform if facilitated," "Ability to overcome shortcomings," "Self-efficacy," "Complexity," and "Perceived usefulness." The item-construct validity index of accepted items was >0.83, and Cronbach's alpha for each construct ranged between 0.70 to 0.96, while factor loading for each item was between 0.723 to 0.963. All results were considered "good" and "excellent." The new tool appears to be valid, reliable, and feasible to measure behavioral factors influencing personal dosimeter use among MRWs, which is helpful to facilitate the planning of interventions to improve behaviors in occupational radiation monitoring.

The Associations Between Workplace Noise, Ototoxic Chemicals, and Tinnitus.

OBJECTIVE: To investigate the occupational risk factors associated with tinnitus in the Australian working population. DESIGN: The research was conducted using data collected from the Australian Workplace Exposure Survey-Hearing, a national cross-sectional study of 4970 workers conducted in 2016 to 2017. Workers were asked if they experienced tinnitus and if they answered affirmatively, they were asked about the frequency and length of the presentations. Based on their answers, each worker was categorized as having no tinnitus or any tinnitus, with an additional group of workers with any tinnitus subcategorized as having constant tinnitus. Exposure assessment was conducted using an automated expert assessment method. Exposures included daily noise (L Aeq,8h ), hand-arm vibration (A(8)), impulse noise, smoking status, styrene, trichloroethylene, toluene, n-hexane, p-xylene, ethylbenzene, lead, and carbon monoxide. Univariate and multivariate logistic regression models were used to examine the associations between workplace exposures and tinnitus. RESULTS: Workers with an estimated noise exposure above the workplace limit (L Aeq,8h > 85 dBA) had 1.73 (95% confidence interval [CI]: 1.42 to 2.11) increased odds of any tinnitus and 2.15 (95% CI: 1.60 to 2.89) odds of constant tinnitus. The odds of workers having any tinnitus increased with increasing noise exposure levels in a dose-response relationship that strengthened when considering only those with constant tinnitus. In the fully adjusted model, statistically significant associations were seen for lead exposure with both any and constant tinnitus, toluene exposure with constant tinnitus, and carbon monoxide exposure with any tinnitus. CONCLUSIONS: These results suggest that, in addition to workplace noise, occupational exposures to lead, toluene, and carbon monoxide are associated with tinnitus.

The association between breast arterial calcification and atherosclerotic cardiovascular disease in an Australian population-based breast cancer case-control study.

PURPOSE: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Breast arterial calcification (BAC) on mammograms is not associated with breast cancer risk. However, there is increasing evidence supporting its association with cardiovascular disease (CVD). This study examines the association between BAC and ASCVD and their risk factors within an Australian population-based breast cancer study. MATERIALS AND METHODS: Data from the controls who participated in the breast cancer environment and employment study (BCEES) were linked with the Western Australian Department of Health Hospital Morbidity database and Mortality Registry to obtain ASCVD outcomes and related risk factor data. Mammograms from participants with no prior history of ASCVD were assessed for BAC by a radiologist. Cox proportional hazards regression was used to examine the association between BAC and later occurrence of an ASCVD event. Logistic regression was used to investigate the factors associated with BAC. RESULTS: A total of 1020 women with a mean age of 60 (sd = 7.0 years) were included and BAC found in 184 (18.0%). Eighty (7.8%) of the 1020 participants developed ASCVD, with an average time to event of 6.2 years (sd = 4.6) from baseline. In univariate analysis, participants with BAC were more likely to have an ASCVD event (HR = 1.96 95% CI 1.29-2.99). However, after adjusting for other risk factors, this association attenuated (HR = 1.37 95% CI 0.88-2.14). Increasing age (OR = 1.15, 95% CI 1.12-1.19) and parity (pLRT < 0.001) were associated with BAC. CONCLUSION: BAC is associated with increased ASCVD risk, but this is not independent of cardiovascular risk factors.

Longitudinal measurements of per- and poly-fluoroalkyl substances (PFAS) in archived human serum samples between 1975 and 1995 in Australia.

Per- and poly-fluoroalkyl substances (PFAS) are a group of manmade compounds produced since the 1950 s and used in a range of industrial processes and consumer products. In Australia, PFAS serum concentrations have been measured in the general population since 2002. However, few studies have retrospectively measured PFAS concentrations in serum samples representative of a general population prior to 2000, none of which have been conducted in Australia. To understand the general population's exposure to PFAS prior to 2002, longitudinal PFAS serum concentration measurements are required. In the current study, we accessed 'The Busselton Health Study Data Bank' to analyse archived serum samples for PFAS. Repeat serum samples collected in 1975, 1981 and 1995 were obtained from 17 participants. Of the 35 PFAS analysed, 13 PFAS were detected in the serum samples collected in 1975. Both the detection frequency and ∑PFAS serum concentrations increased between 1975 and 1995. Median ∑PFAS serum concentration increased over 7-fold; from 3.3 ng/mL in 1975-26 ng/mL in 1995. The increase in serum concentrations reflects the global production history of these PFAS during this period in time.

Factors Influencing the Use of Control Measures to Reduce Occupational Exposure to Welding Fume in Australia: A Qualitative Study.

Background: Exposure to welding fume is associated with adverse effects on worker health. The use of various control measures can reduce levels of exposure and the resulting health effects. However, little is known about the factors that may influence workers' use of control measures in the workplace and their perceived intervention needs. This study aimed to investigate workers' and other stakeholders' views on ways to improve the use of welding fume control measures in Australian workplaces. Methods: We conducted a series of online focus group discussions and individual interviews with participants who have some occupational involvement in welding, whether as workers, employers or industry representatives, union representatives, or regulators. A semi-structured question guide was used, and all discussions and interviews were recorded and transcribed for analysis. Results: Five focus group discussions and five individual interviews were conducted with a total of 21 participants. Three major themes emerged. The first addressed the current awareness of welding fume harms and concern about exposure; the second focussed on the current use of control measures, and barriers and facilitators to their use; and the last centred around intervention needs and the contents of a potential effective intervention. Conclusion: Improving the use of control measures to prevent exposure to welding fume requires knowledge around the barriers and facilitators of control, use, and the intervention needs of stakeholders. This study has provided such knowledge, which will facilitate the design and implementation of an intervention to reduce welding fume exposure and ultimately protect the health of workers.

Comparison of agreement in asthmagen exposure assessments between rule-based automatic algorithms and a job exposure matrix in healthcare workers in Australia and Bhutan.

BACKGROUND: Assessment of occupational exposures is an integral component of population-based studies investigating the epidemiology of occupational diseases. However, all the available methods for exposure assessment have been developed, tested and used in high-income countries. Except for a few studies examining pesticide exposures, there is limited research on whether these methods are appropriate for assessing exposure in LMICs. The aim of this study is to compare a task-specific algorithm-based method (OccIDEAS) to a job-specific matrix method (OAsJEM) in the assessment of asthmagen exposures among healthcare workers in a high-income country and a low- and middle- income country (LMIC) to determine an appropriate assessment method for use in LMICs for future research. METHODS: Data were obtained from a national cross-sectional survey of occupational asthmagens exposure in Australia and a cross-sectional survey of occupational chemical exposure among Bhutanese healthcare workers. Exposure was assessed using OccIDEAS and the OAsJEM. Prevalence of exposure to asthmagens and inter-rater agreement were calculated. RESULTS: In Australia, the prevalence was higher for a majority of agents when assessed by OccIDEAS than by the OAsJEM (13 versus 3). OccIDEAS identified exposures to a greater number of agents (16 versus 7). The agreement as indicated by κ (Cohen's Kappa coefficient) for six of the seven agents assessed was poor to fair (0.02 to 0.37). In Bhutan, the prevalence of exposure assessed by OccIDEAS was higher for four of the seven agents and κ was poor for all the four agents assessed (-0.06 to 0.13). The OAsJEM overestimated exposures to high-level disinfectants by assigning exposures to all participants from 10 (Bhutan) and 12 (Australia) ISCO-88 codes; whereas OccIDEAS assigned exposures to varying proportions of participants from these ISCO-codes. CONCLUSION: There was poor to fair agreement in the assessment of asthmagen exposure in healthcare workers between the two methods. The OAsJEM overestimated the prevalence of certain exposures. As compared to the OAsJEM, OccIDEAS appeared to be more appropriate for evaluating cross-country exposures to asthmagens in healthcare workers due to its inherent quality of assessing task-based determinants and its versatility in being adaptable for use in different countries with different exposure circumstances.

Herbicide use in farming and other jobs in relation to non-Hodgkin's lymphoma (NHL) risk.

OBJECTIVES: Given mixed evidence for carcinogenicity of current-use herbicides, we studied the relationship between occupational herbicide use and risk of non-Hodgkin's lymphoma (NHL) in a large, pooled study. METHODS: We pooled data from 10 case-control studies participating in the International Lymphoma Epidemiology Consortium, including 9229 cases and 9626 controls from North America, the European Union and Australia. Herbicide use was coded from self-report or by expert assessment in the individual studies, for herbicide groups (eg, phenoxy herbicides) and active ingredients (eg, 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate). The association between each herbicide and NHL risk was estimated using logistic regression to produce ORs and 95% CIs, with adjustment for sociodemographic factors, farming and other pesticides. RESULTS: We found no substantial association of all NHL risk with ever-use of any herbicide (OR=1.10, 95% CI: 0.94 to 1.29), nor with herbicide groups or active ingredients. Elevations in risk were observed for NHL subtypes with longer duration of phenoxy herbicide use, such as for any phenoxy herbicide with multiple myeloma (>25.5 years, OR=1.78, 95% CI: 0.74 to 4.27), 2,4-D with diffuse large B-cell lymphoma (>25.5 years, OR=1.47, 95% CI: 0.67 to 3.21) and other (non-2,4-D) phenoxy herbicides with T-cell lymphoma (>6 years, lagged 10 years, OR=3.24, 95% CI: 1.03 to 10.2). An association between glyphosate and follicular lymphoma (lagged 10 years: OR=1.48, 95% CI: 0.98 to 2.25) was fairly consistent across analyses. CONCLUSIONS: Most of the herbicides examined were not associated with NHL risk. However, associations of phenoxy herbicides and glyphosate with particular NHL subtypes underscore the importance of estimating subtype-specific risks.

Estimate of Occupational Exposure to Carcinogens among Migrant Workers in the United Arab Emirates: A Cross-Sectional Study.

Occupational illnesses, such as cancer, cause more deaths each year than occupational accidents. Occupational carcinogens include physical, chemical, biological and organizational hazards. In the United Arab Emirates (UAE), migrant workers account for 80% of labor. Being sometimes employed as unskilled workers and more willing to work in demanding jobs, their vulnerability and exposure may be increased. This study aimed to estimate the prevalence of occupational exposure to workplace carcinogens among migrant workers in the UAE. A sample of employees working in construction, cleaning, dry cleaning, mechanic workshops and hair salons were recruited and interviewed. Using OccIDEAS (an online assessment tool), participants were asked questions about their demographics, work history and regular tasks. Exposure to various carcinogens was estimated using the in-built algorithms of OccIDEAS. A sample of 1778 workers was included. The sample consisted of workers from Bangladesh (19.2%), India (31%), Nepal (4.7%), Pakistan (29.9%) and the Philippines (4.8%), with the rest from other nationalities. Overall, the prevalence of probable exposure was considerable, with the highest among drivers (96%) and the lowest among laundry workers (52%). Moderate to high exposure was found to 20 different carcinogens. Self-rated health among those who were exposed to carcinogens was significantly lower than among those not exposed (AOR = 0.783, 95% CI [0.638-0.961]). Exposure to several different carcinogens is relatively common in the UAE among migrant workers. Further strengthening policies and the implementation of tailored interventions are needed to prevent exposure to occupational carcinogens and, consequently, to combat occupational cancer in the UAE.

Occupational noise exposure of utility workers using task based and full shift measurement comparisons.

Introduction: The main purpose of this study was to determine if a combination of area noise measurements and task activity diaries give a reasonable estimate of full-shift dosimeter measurements in a cohort of utility workers. Few studies have been conducted to evaluate the efficacy of using task-based noise exposures to estimate full shift time weighted average (TWA) noise exposures. Methods: Estimates of full shift time TWA noise exposures for a group of utility workers (n = 224) were calculated using dosimeter measurements. Area noise measurements using a sound level meter were used to recreate the TWA for each personal dosimetry sample based on detail provided in the task activity diary for each sample. Full shift TWA noise exposures were compared to corresponding area noise measurements using simple linear regression analysis. Results: Associations between full shift TWA measurements and task-based area measurements were closely associated, with R2 values above 0.85 for all job roles. Discussion: Task-based noise exposure analysis has the potential to be widely used in the utilities industry. While full-shift monitoring to determine TWA exposures is useful, the changing work environment, variability in tasks and equipment, and varying workday hours, limit the ability of the 8-hr TWA to accurately characterise the exposures and associated health risks for utility workers.

Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies.

BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. RESULTS: Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like. CONCLUSIONS: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

Use of expert elicitation in the field of occupational hygiene: Comparison of expert and observed data distributions.

The concept of professional judgement underpins the way in which an occupational hygienist assesses an exposure problem. Despite the importance placed on professional judgement in the discipline, a method of assessment to characterise accuracy has not been available. In this paper, we assess the professional judgement of four occupational hygienists ('experts') when completing exposure assessments on a range of airborne contaminants across a number of job roles within a surface mining environment in the Pilbara region of Western Australia. The job roles assessed were project driller, mobile equipment operator, fixed plant maintainer, and drill and blast operator. The contaminants of interest were respirable crystalline silica, respirable dust, and inhalable dust. The novel approach of eliciting exposure estimates focusing on contaminant concentration and attribution of an exposure standard estimate was used. The majority of the elicited values were highly skewed; therefore, a scaled Beta distribution were fitted. These elicited fitted distributions were then compared to measured data distributions, the results of which had been collected as part of an occupational hygiene program assessing full-shift exposures to the same contaminants and job roles assessed by the experts. Our findings suggest that the participating experts within this study tended to overestimate exposures. In addition, the participating experts were more accurate at estimating percentage of an exposure standard than contaminant concentration. We demonstrate that this elicitation approach and the encoding methodology contained within can be applied to assess accuracy of exposure judgements which will impact on worker protection and occupational health outcomes.

Rare germline copy number variants (CNVs) and breast cancer risk.

Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.

The prevalence of tinnitus in the Australian working population.

OBJECTIVES: To estimate the prevalence of tinnitus in Australian working people; to identify occupational and demographic factors associated with tinnitus. DESIGN: Cross-sectional national telephone survey of self-reported frequency and duration of tinnitus. SETTING, PARTICIPANTS: Australian Workplace Exposure Survey (AWES) - Hearing; 4970 currently employed people aged 18-64 years, recruited by random digit dialling, representative by sex of the workforce population, 7 June 2016 - 20 March 2017. MAIN OUTCOME MEASURES: Prevalence of occasional, intermittent, and constant tinnitus, and of any tinnitus, by occupational group, sex, and other demographic characteristics; estimated numbers of working people with constant or any tinnitus, by occupational group and sex. RESULTS: Of 4970 respondents, 1317 reported experiencing tinnitus (26.5%): 713 people had occasional tinnitus (14.3%), 259 intermittent tinnitus (5.2%), and 345 constant tinnitus (6.9%). The sample prevalence of constant tinnitus was greater among men (7.5%; 95% CI, 6.2-8.7%) than women (3.3%; 95% CI, 2.3-4.3%), and was higher in older age groups. After rake weighting our survey responses, we estimated that 2.4 million workers (24.8%; 95% CI, 23.2-26.4%) experience tinnitus, including 529 343 with constant tinnitus (5.5%; 95% CI, 4.6-6.3%). The estimated prevalence of constant tinnitus was highest for automotive workers (16.7%; 95% CI, 9.5-23.8%), drivers (13.0%; 95% CI, 7.3-18.6%), farmers (12.1%; 95% CI, 5.9-18.4%), and workers in other trades (10.4%; 95% CI, 4.6-16.2%). CONCLUSIONS: The prevalence of tinnitus in the Australian workforce is high, particularly in certain occupations. Workplace practices and conditions that increase the risk of tinnitus should be examined, and targeted workplace prevention strategies developed.

Spatial disparities in the reported incidence and survival of myeloproliferative neoplasms in Australia.

Myeloproliferative neoplasms (MPNs) are an uncommon group of blood cancers that, if untreated, result in an increased risk of haemorrhagic event or thrombosis. Unlike other cancer types, diagnosis of MPNs requires a combination of microscopic, clinical and genetic evidence, which provide unique challenges given the typical notification processes of cancer registries. This, and the relatively recent advances in diagnosis and revision of the World Health Organization diagnostic criteria, may result in under-diagnosis or under-reporting of MPNs. We used population-based cancer registry data from the Australian Cancer Database and modelled the incidence and survival of MPNs between 2007 and 2016 using generalised linear models and Bayesian spatial Leroux models. Substantial evidence was found of spatial heterogeneity in the incidence of MPNs and significant differences in incidence and survival by state or territory. States with lower incidence tended to have poorer survival, suggesting that some less severe cases may not be diagnosed or notified to the registries in those states. Population rates of genetic testing and percentages of records diagnosed using bone marrow biopsies did not explain the differences in incidence by state and territory. It is important to determine the key drivers of these geographical patterns, including the need to standardise diagnosis and reporting of MPNs.

The future excess fraction of cancer due to lifestyle factors in Australia.

BACKGROUND: Many cancers are caused by exposure to lifestyle, environmental, and occupational factors. Earlier studies have estimated the number of cancers occurring in a single year which are attributable to past exposures to these factors. However, there is now increasing appreciation that estimates of the future burden of cancer may be more useful for policy and prevention. We aimed to calculate the future number of cancers expected to arise as a result of exposure to 23 modifiable risk factors. METHODS: We used the future excess fraction (FEF) method to estimate the lifetime burden of cancer (2016-2098) among Australian adults who were exposed to modifiable lifestyle, environmental, and occupational risk factors in 2016. Calculations were conducted for 26 cancer sites and 78 cancer-risk factor pairings. RESULTS: The cohort of 18.8 million adult Australians in 2016 will develop an estimated 7.6 million cancers during their lifetime, of which 1.8 million (24%) will be attributable to exposure to modifiable risk factors. Cancer sites with the highest number of future attributable cancers were colon and rectum (n = 717,700), lung (n = 380,400), and liver (n = 103,200). The highest number of future cancers will be attributable to exposure to tobacco smoke (n = 583,500), followed by overweight/obesity (n = 333,100) and alcohol consumption (n = 249,700). CONCLUSION: A significant proportion of future cancers will result from recent levels of exposure to modifiable risk factors. Our results provide direct, pertinent information to help determine where preventive measures could best be targeted.

Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.

BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). RESULTS: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. CONCLUSIONS: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.