W. Jay Christian

Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

Background Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01–1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15–2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79–1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84–0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25–2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.

Human papillomavirus vaccine: knowledge and attitudes in two Appalachian Kentucky counties

ObjectiveA vaccine against common high-risk types of human papillomavirus (HPV) associated with cervical cancer risk was recently approved. We assessed women’s acceptance of HPV vaccination for themselves and for adolescent girls, in an Appalachian population with cervical cancer incidence and mortality rates among the highest in the United States.MethodsWe conducted a population-based, random-digit telephone survey of over 600 adult women residing in two Appalachian Kentucky counties. The analysis focused on questions of HPV vaccine acceptance, and their relationship to several factors.ResultsThe majority of women indicated an interest in HPV vaccination for themselves (85.2%), but they were less accepting of a vaccine being administrated to girls of ages 10–15 (67.6%). Women who were younger, lower-income and smokers were more likely to support vaccination.ConclusionsAlthough a relatively high percentage of women found the HPV vaccination acceptable for their own use, there was less enthusiasm for supporting vaccination to girls. This finding is of concern since the vaccine is being recommended for adolescent girls and young women, prior to sexual initiation. Educational campaigns will be needed for a successful vaccine implementation.

Acceptance of the HPV vaccine for adolescent girls: analysis of state-added questions from the BRFSS.

PURPOSE Previous research regarding human papillomavirus (HPV) awareness and vaccine acceptance has relied on convenience or other selected samples of the population. To assess the prevalence of HPV awareness and vaccine acceptance in Kentucky we added questions to the 2006 Kentucky Behavioral Risk Factor Survey System (BRFSS), a population-based survey of health behaviors. METHODS Women who participated in the statewide BRFSS were asked two HPV-related questions: one assessed previous awareness of HPV, and another assessed vaccine acceptance for girls 10 to 15 years old. We used crosstabulations and multivariate logistic regression to determine which factors were associated with HPV awareness and vaccine acceptance. Because the HPV vaccine Gardasil was approved in June 2006, we conducted an analysis of pre- and postapproval HPV awareness and vaccine acceptance. We also compared results across Appalachian and non-Appalachian counties, two distinct regions of Kentucky. RESULTS Overall, 57.6% of women had heard of HPV, and 70.2% accepted vaccination for girls. HPV awareness increased after Gardasils approval, but the increase was much smaller among Appalachian women. Prevalence of vaccine acceptance was unchanged in both regions. Awareness of HPV was not associated with vaccine acceptance, and factors significantly associated with vaccine acceptance in multivariate analysis differed by Appalachian status. CONCLUSIONS This population-based survey of Kentucky women found relatively high vaccine acceptance for girls. Also, many respondents reported not knowing whether they accept vaccination, and factors associated with vaccine acceptance varied by Appalachian status. These findings suggest that acceptance of the HPV vaccine for girls may improve with targeted interventions.

Using geospatial technologies to explore activity-based retail food environments.

Several studies have demonstrated relationships between neighborhood-level retail food environments and obesity, race/ethnicity, and socioeconomic status. Most, however, have been limited by the use of residential neighborhoods to define food environments. This study recruited 121 participants to supply three days of Global Positioning System (GPS) tracking data to explore daily activity spaces and food environments. Participants also answered two surveys regarding personal characteristics, and diet and food purchasing. Several food environment measures were calculated for food locations within a half-mile of their GPS tracks. Non-parametric statistics examined (1) differences between activity- and neighborhood-based food environments, (2) associations between personal characteristics and activity-based food environments, and (3) associations between diet, purchasing, and activity-based food environments. Activity- and neighborhood-based food environments were significantly different. Several associations were observed among activity-based food environment measures and personal characteristics. Dietary intake, food purchasing, and obesity were associated with some activity-based food environment measures.

Variability of cervical cancer rates across 5 Appalachian states, 1998–2003†‡

Although the rates of invasive cervical cancer (ICC) have decreased substantially in the US since the advent of the Papanicolaou (Pap) test, Appalachian women remain at increased risk compared with the nation as a whole. The ICC incidence rates were compared in 5 Appalachian states with population‐based cancer registries to investigate variability within the Appalachian region.

Exploring Geographic Variation in Lung Cancer Incidence in Kentucky Using a Spatial Scan Statistic: Elevated Risk in the Appalachian Coal-Mining Region

Objectives. We examined geographic patterns of lung cancer incidence in Kentucky. Recent research has suggested that the coal-mining industry contributes to lung cancer risk in Appalachia. We focused on the southeastern portion of the state, which has some of the highest lung cancer rates in the nation. Methods. We implemented a spatial scan statistic to identify areas with lung cancer incidence rates that were higher than expected, after adjusting for age, gender, and smoking. The Kentucky Cancer Registry supplied information on cases (1995–2007). The U.S. Census (2000) and several years of Behavioral Risk Factor Surveillance System data (1996–2006) provided county-level population and smoking data. We compared the results with coal-mining data from the Mining Safety and Health Administration and public water utility data from the Kentucky Division of Water. Results. We identified three clusters of counties with higher-than-expected rates. Cluster 1 (relative risk [RR] = 1.21, p<0.01) included 12 counties in southeastern Kentucky. Cluster 2 (RR=1.17, p<0.01) included three nearby counties in the same region. Several of the 15 counties in Cluster 3 (RR=1.04, p=0.01) were part of the Louisville, Kentucky, or Cincinnati, Ohio, metropolitan areas. All of the counties in Clusters 1 and 2 produced significant amounts of coal. Conclusion. Environmental exposures related to the coal-mining industry could contribute to the high incidence of lung cancer in southeastern Kentucky. Lack of evidence for this effect in western Kentucky could be due to regional differences in mining practices and access to public water utilities. Future research should collect biological specimens and environmental samples to test for the presence of trace elements and other lung carcinogens.

Population Cancer Risks Associated with Coal Mining: A Systematic Review

Background Coal is produced across 25 states and provides 42% of US energy. With production expected to increase 7.6% by 2035, proximate populations remain at risk of exposure to carcinogenic coal products such as silica dust and organic compounds. It is unclear if population exposure is associated with increased risk, or even which cancers have been studied in this regard. Methods We performed a systematic review of English-language manuscripts published since 1980 to determine if coal mining exposure was associated with increased cancer risk (incidence and mortality). Results Of 34 studies identified, 27 studied coal mining as an occupational exposure (coal miner cohort or as a retrospective risk factor) but only seven explored health effects in surrounding populations. Overall, risk assessments were reported for 20 cancer site categories, but their results and frequency varied considerably. Incidence and mortality risk assessments were: negative (no increase) for 12 sites; positive for 1 site; and discordant for 7 sites (e.g. lung, gastric). However, 10 sites had only a single study reporting incidence risk (4 sites had none), and 11 sites had only a single study reporting mortality risk (2 sites had none). The ecological study data were particularly meager, reporting assessments for only 9 sites. While mortality assessments were reported for each, 6 had only a single report and only 2 sites had reported incidence assessments. Conclusions The reported assessments are too meager, and at times contradictory, to make definitive conclusions about population cancer risk due to coal mining. However, the preponderance of this and other data support many of Hill’s criteria for causation. The paucity of data regarding population exposure and risk, the widespread geographical extent of coal mining activity, and the continuing importance of coal for US energy, warrant further studies of population exposure and risk.

Factors associated with smoking abstinence after diagnosis of early stage lung cancer

Smoking cessation after a diagnosis of lung cancer is associated with improved outcomes, including quality of life and survival. The research presented here is based on data obtained from sequential interviews with early stage lung cancer patients in Kentucky, on their smoking patterns at four time points: (1) six months before enrollment in the study, before diagnosis, (2) at enrollment (shortly after surgical resection), (3) three months post-enrollment, and (4) six months post-enrollment. A number of covariates were considered to examine the factors associated with smoking abstinence and rebound trajectories. The results indicate that, while about 75% of patients who were smoking at six months before enrollment had quit by the first post-surgery interview, almost 50% of them had returned to smoking six months later. Multivariate analysis to evaluate the relative contribution of covariates indicated that low household income, exposure to environmental tobacco smoke at home and evidence of depression were positively associated with returning to smoking. Furthermore, even after controlling for these factors, patients from the Appalachian region of Kentucky, an area with substantially high smoking prevalence and very high lung cancer incidence rates, were less likely to abstain from smoking throughout the study than subjects in the rest of the state. Future research is suggested to investigate in more detail the tobacco-related behaviors and cessation attempts of patients and their families, which can lead to more targeted, successful smoking cessation interventions for lung cancer patients.

Rural-Urban Differences in Alzheimer's Disease and Related Disorders Diagnostic Prevalence in Kentucky and West Virginia

PURPOSE Older adults living in rural areas may face barriers to obtaining a diagnosis of Alzheimers disease and related disorders (ADRD). We sought to examine rural-urban differences in prevalence of ADRD among Medicare beneficiaries in Kentucky and West Virginia, 2 contiguous, geographically similar states with large rural areas and aged populations. METHODS We used Centers for Medicare and Medicaid Services Public Use Files data from 2007 to 2013 to assess prevalence of ADRD at the county level among all Medicare beneficiaries in each state. Rural-Urban Continuum Codes were used to classify counties as rural or urban. We used Poisson regression to estimate unadjusted and adjusted prevalence ratios. Primary analyses focused on 2013 data and were repeated for 2007 to 2012. This study was completely ecologic. FINDINGS After adjusting for state, average beneficiary age, percent of female beneficiaries, percent of beneficiaries eligible for Medicaid in each county, Central Appalachian county, percent of age-eligible residents enrolled in Medicare, and percent of residents under age 65 enrolled in Medicare in our adjusted models, we found that 2013 ADRD diagnostic prevalence was 11% lower in rural counties (95% CI: 9%-13%). CONCLUSIONS Medicare beneficiaries in rural counties in Kentucky and West Virginia may be underdiagnosed with respect to ADRD. However, due to the ecologic design, and evidence of a younger, more heavily male beneficiary population in some rural areas, further studies using individual-level data are needed to confirm the results.

Abstract 2526: Coal mining and cancer risk: important gaps in public health knowledge.

Coal fueled 42% of electricity generation in the US in 2011 with >1 billion tons mined across 27 states. Considering that 33% of petroleum used in the US comes from Arab States and Venezuela, coal will remain a critical component of US energy policy with national production expected to increase 7.6% by 2035. Given the large spatial extent of coal bearing formations, substantial proportions of the population are now, with more likely to be, exposed to coal mining (CM) activities, e.g. dust from mining and processing, leachates from mine tailings, and smoke from coal combustion. While CM activities are known to release carcinogens such as crystalline silica dust, polyaromatic hydrocarbons, and trace elements (e.g. Cd, As), a systematic review of literature published since 1980 regarding resultant impacts upon cancer rates in potentially exposed populations is equivocal. Occupational studies are designed to provide data concerning the effects of acute or long term exposure. Of 11 such studies identified, 7 found an increased risk of cancer in coal miners (digestive/gastric, lung, all cancers) but 4 found no increased risk (gastric, lung, all cancers). Another 17 studies compared miners to other populations, or examined CM as a risk factor. Nine found associations between CM and increased cancer risk (bladder, gastric, larynx, lung, nasal, all cancers), but 8 found no increased risk (gastric, lung). Finally, 6 studies were identified which examined associations between CM and cancer in the general population. Three found associations between community cancer rates and CM, with those living near CM at increased risk (male colorectal, lung), 2 used spatial statistics to identify cancer clusters associated with CM (breast, lung, respiratory, all cancers), and 1 used community surveys to identify increased self-reported cancer in mining areas. While the strength of these latter studies is limited by weaknesses inherent in ecological and cross-sectional designs, evidence exists to support the biological plausibility that populations near CM activities are at increased risk. Environmental studies have shown that lignite bed leachates are associated with renal pelvic cancer and induce kidney cell culture proliferation; rodents captured from CM areas had greater DNA damage than non-exposed controls; and crystalline silica may be found in coal at high levels and released by burning. In sum, the data are too weak to conclude there is an increased risk of cancer to the general population, to identify which specific populations suffer that risk, or indicate which mitigation strategies may be effectively implemented. While prospective cohort studies might provide such data, the long lag time between exposure and cancer may preclude practicality and other measures of exposure (e.g. toenail clippings, wind patterns) and potential pre-cancerous cellular conditions (e.g. DNA methylation, histone modifications) should be investigated as interim outcomes. Citation Format: Wiley D. Jenkins, Georgia Mueller, W. Jay Christian. Coal mining and cancer risk: important gaps in public health knowledge. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2526. doi:10.1158/1538-7445.AM2013-2526