Family History Of Lung Cancer Research Articles

Factors influencing lung cancer screening completion following participation in shared decision-making: A retrospective study in a U.S. academic health system

PurposeShared decision making (SDM) between patients and designated health professionals is recommended by several professional organizations prior to lung cancer screening by low dose CT (LDCT). This study seeks to identify factors, including characteristics of patients and referring clinicians, that influence LDCT screening completion following participation in SDM. Materials and methodsThis retrospective study consisted of n = 171 patients eligible for LDCT screening and who participated in SDM between 2016 and 2017 in one of two sites in Prisma Health, an academic health care delivery system in South Carolina. Patient characteristics included age, sex, race, body mass index, marital status, insurance, smoking status and history, family history of lung cancer, SDM site, and distance to screening site. Characteristics of referred clinicians included age, sex, race, specialty, years of practice, education, and residency. Descriptive statistics and multivariable generalized linear mixed models were used to compare effects of patient and referring clinician characteristics on LDCT completion. ResultsA total of 152 patients (89%) completed LDCT screening after participation in SDM. SDM site (p = 0.02), longer distances to the screening site (p = 0.03), referrals from internal medicine clinicians (p = 0.03), and referrals from younger clinicians (p = 0.01) and from those with less years of experience (p = 0.02) were significantly associated with a lower likelihood of screening completion. ConclusionsSeveral factors significantly associated with screening completion were identified. This information can assist with development of interventions to improve communication and decision-making between patients, clinicians, and SDM health professionals, and inform design of targeted decision aids embedded into SDM procedures.

PD1.03 A Primer on Genetic Counseling on the Thoracic Oncology Unit. Family History of Lung Cancer in Two Independent Populations Tested for BRCA1 & amp;2 and EGFR.

PD1.03 A Primer on Genetic Counseling on the Thoracic Oncology Unit. Family History of Lung Cancer in Two Independent Populations Tested for BRCA1 & amp;2 and EGFR.

EP1.12-40 Neuroendocrine Tumors of the Lung: Clinico-Pathological Characterization and Follow-Up of Patients Treated at an Argentinean University Hospital in the Last 10 Years

Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, most commonly from the lungs and gastrointestinal tract. Histological characteristics and clinical behaviour define lung NETs, which are classified into four groups: typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine carcinoma (LCNC) and small-cell lung cancer (SCLC). The identification and differentiation of TCs from ACs or LCNECs and SCLC is essential for treatment options and prognosis. We performed a retrospective review of patients with lung NETs treated in our institution in the last decade. We analysed histological confirmed primary lung NETs cases. Demographics, clinical characteristics, imaging, treatment and outcome are described for this patient population. A total of 91 patients with lung NETs were included; 28/91 (30.8%) were lung carcinoids (TC:14 and AT: 14) and 63/91 (69.2%) were high grade lung NETs (SCLC: 54 and LCNC: 9). Comparing low and high grade NETs groups of patients, we could identify differences in the following variables: mean age at diagnosis (51±14 vs 61 ±9 years, p=0.000), mean time from the beginning of symptoms to achievement of pathologic diagnosis (10.5±15.9 vs 3.9 ± 2.6 months, p=0.002), ECOG³2 (14% vs 42%, p=0.001), smokers (57% vs 95%, p=0.000), median % of Ki67 expression (4%, (1-30%) vs 50%, (20-90), p=0.000), history of inflammatory lung disease (18% vs 32%, p=0.028) and presence extra-thoracic disease at diagnosis (47% vs 68%, p=0.000). No statistically differences between groups were observed in: sex, family history of lung cancer, second diagnosis of cancer and body mass index at diagnosis. Functioning carcinoid syndrome was observed in 10% (3/28) of patients with lung carcinoids. For the entire cohort, the median overall survival (OS) was 19 months (IC95%: 14-24 months). The five year OS for patients with lung carcinoids was 62% and 13% for high grade NETs. In our series of lung carcinoids we observed a high frequency of: atypical carcinoids, advanced disease at presentation and smoking history. However, the 5-year overall survival is the expected for this population. More knowledge is needed about this entity in South American countries.

ROUNDED ATELECTASIS: IS IT TRULY BENIGN?

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Rounded Atelactasis (RA) is a special type of peripheral lung collapse associated with focal pleural thickening, typically attributed to asbestos inhalation(1). RA is usually benign, and does not require any intervention, and is often misdiagnosed as a malignant lesion requiring patients to undergo unnecessary interventions. The co-existence of RA and lung cancer has been rarely reported in literature. Here, we present a 67-year-old male with RA, that was subsequently followed with a biopsy ten years later revealing adenocarcinoma. CASE PRESENTATION: 67-year-old male with minimal smoking history and medical history of hypertension, dyslipidemia presented outpatient as referral for an abnormal finding on his Cardiac CT for calcium scoring. Patient denied cough, shortness of breath, weight loss, hemoptysis, pleuritic chest pain and night sweats. All other review of system questions were answered in negative. Occupational history was positive for asbestos exposure but no family history of lung cancer. Physical exam was positive for mild decrease air entry on the left side. No clubbing, or lymphadenopathy was seen. Spirometry showed FVC and FEV1 of 59% and 54% of predicted respectively with FEV1/FVC ratio of 70. Previous CT chest from 2007 revealed bilateral pleural plaques and thickened pleura with 3 cm RA in left lower lobe. Repeat CT chest from 2010 showed stable 3 cm mass-like opacity likely representing RA with no evidence of parenchymal fibrosis. CT chest from 2018 showed interval increase in size of left lower lobe mass to 4.8 cm at the site of previous RA. Subsequent PET-CT showed increased uptake about the lesion, which was subsequently biopsied. Microscopically, tumor cells were positive for Napsin A and TTF-1, and no necrosis was appreciated in the biopsy sample. A histopathologic diagnosis of moderately differentiated adenocarcinoma was established. Patient has since been followed by our team and oncology as outpatient. DISCUSSION: RA results from in-folding of the lung in the presence of pleural fluid and fibrinous pleuritis(2). RA appears as a pleural-based mass-like lesion with a rounded shadow 2.5-5 cm in diameter lying along the lower lobe(3). CT typically shows a sharply marginated and homogeneous subpleural mass and volume loss in the affected lung, associated with adjacent pleural effusion or thickening, incurving vessels and bronchi, acute angles with pleura, and sharp lateral margins(4,5). CONCLUSIONS: Our patient possibly had stable RA initially that was later complicated by an underlying malignant process; a rare presentation with both entities co-existing independently of each other. This case educates us to be more aware of RA masking a potential underlying malignant process making it imperative to have recommended guidelines for follow-up of such lesions. Reference #1: Batra P, Brown K, Hayashi K, Mori M. Rounded atelectasis. Journal of Thorac Imaging. 1996;11(3): 187–197. Reference #2: Fraser RS, Muller NL, Colman N, Pare PD. Diagnosis of diseases of the chest, 4th ed. Philadelphia, PA: W. B. Saunders,1999 : 521–522. Reference #3: Schneider, H., Felson, B., & Gonzalez, L. (1980). Rounded atelectasis. American Journal of Roentgenology,134(2), 225-232. https://doi.org/10.2214/ajr.134.2.225 Doyle TC, Lawler GA. CT features of rounded atelectasis of the lung. AJR 1984; 143:225 –228 O'Donovan PB, Schenk M, Lim K, Obuchowski N, Stoller JK. Evaluation of the reliability of computed tomographic criteria used in the diagnosis of rounded atelectasis. J Thorac Imaging 1997; 12:54 –58. DISCLOSURES: No relevant relationships by Anas Al-khateeb, source=Web Response No relevant relationships by Sharath Bellary, source=Web Response No relevant relationships by Muqueet Kadri, source=Web Response No relevant relationships by Saraswathi Lakkasani, source=Web Response No relevant relationships by Richard Miller, source=Web Response No relevant relationships by Rutwik Patel, source=Web Response No relevant relationships by Hari Sharma, source=Web Response

EP1.11-11 Familial Lung Cancer: A Call for Action

Lung cancer (LC) is the most deadly of all cancers mostly due to the fact that the disease is often detected at an advanced stage with less effective treatment options. While 80% of lung cancers can be directly attributable to tobacco smoking, the disease has been increasing in non smokers raising awareness to other risk factors that could be screened for and controlled in order to achieve higher rates of early stage diagnosis. A retrospective analysis of the electronic records of LC patients followed in our district hospital between May 2012 and December 2018 was conducted. Patients with family history of cancer were selected and their demographic characteristics, smoking status, co morbidities and LC characteristics were analyzed. A total of 524 patients were followed, 33 of whom with a positive family history of cancer (20 men and 13 women, median age of 61.7years old at diagnosis ± 12.8 years). Only 9 were never smokers and 63.6% (21) were diagnosed following the investigation of symptoms. The majority (24) had an adenocarcinoma subtype (3 EGFR mutations, 1 ALK translocation and 2 HER2 amplification were identified). Twenty patients (60.6%) had a family history of LC and the most frequent family member affected were parents (father: 14; mother: 11) and siblings (11). Cancer affected at least 2 family members of 15 patients. At the time of diagnosis 19 of the 20 patients with LC family history had an ECOG Performance Status of 0-1 and 8 (40%) had advanced stage disease. We found no significant difference in stage at diagnosis, smoking status or symptoms at diagnosis between patients with and without a LC family history of malignancy (p=0,120, p=0,117 and p=0,814 respectively). Studies demonstrating evidence of familiar aggregation of LC suggest a possible genetic susceptibility to this malignancy. Identification of individuals at particularly high risk of lung cancer due to this type of susceptibility would contribute to early detection and possibly to prevention through targeted and intense anti-smoking efforts. Perhaps due to the small dimension of our study population, our patients were not diagnosed in early stages of the disease despite a positive family history of lung cancer. This raises the question whether this particular group of people should be selected for specific cancer screening to allow for the possibility of curative treatments.

P2.11-37 Low-Dose CT Lung Screening: Analysis of Risk Factors Related to Lung Cancer

LDCT has been increasingly accepted as an efficient screening method for lung cancer detection and mortality reduction in high-risk populations. Screening data based lung cancer risk factors analysis is supposed to benefit identifying high-risk population of lung cancer. The aims of this study are to provide data support for identifying high-risk groups of lung cancer and to improve the effectiveness of LDCT lung cancer screening. Subjects consisted of 5366 asymptomatic and voluntary participants (includes 2762 males and 2604 females) aged 40-87 years old, who received LDCT in Cancer Hospital, Chinese Academy of Medical Sciences between Jan 1st, 2014 and Dec 31st, 2017. Participants finished questionnaires relevant to risk factors and were provided Low-dose CT scans. The LDCT Radiological results were interpreted according to the I-ELCAP lung Screening Protocol. Multivariate logistic regression examined associations of risk factors within Age, Sex, Smoking status, Second-hand smoking status, COPD, Asthma, Family history of lung cancer, History of tuberculosis, Occupational exposure and Diabetes. 389 of the 5366 participants had a positive (including lung cancer) screen with LDCT, 26 participants were pathologically confirmed lung cancer. Multivariate logistic regression showed that age and smoking (previous smoking and current smoking) were risk factors related to lung cancer and positive nodules. There was no risk factor in distinguishing between lung cancer and positive nodules (excluded lung cancer). Stratified by age, Multivariate logistic regression did not identify any risk factor related to lung cancer and positive nodules in 40-49 years old group, while 3 risk factors were identified in ≥50 years old group (age, smoking, and history of tuberculosis).View Large Image Figure ViewerDownload Hi-res image Download (PPT) • Age, smoking are risk factors related to lung cancer and positive nodules. • ≥50 years old with a history of smoking or tuberculosis may be a high risk group for lung cancer in China.

P2.11-23 Performance of Lung Cancer Risk Prediction Models in I-ELCAP Smokers

To determine the performance of lung cancer risk prediction models in predicting lung cancer in smokers enrolled in the International Early Lung Cancer Program (I-ELCAP). 62,071 asymptomatic ever-smokers enrolled into the international multi-institutions I-ELCAP for low-dose CT screening between 1993-2018. Demographics, smoking history, comorbidities, exposures and family history of lung cancer were collected at time of baseline CT scan. All participants received a baseline screening scan and subsequently annual repeat CT scans, and they were prospectively followed for the diagnosis of lung cancer. Diagnosis and treatment of lung cancer were verified and documented in the ELCAP Management System. To compare the predicted risk of lung cancer, we applied four lung cancer risk models: the Bach Model, the Liverpool Lung Project Incidence (LLPi) Risk model, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 (PLCOM2012), and the Pittsburgh Predictor Model to the I-ELCAP cohort. Model calibration and discrimination were assessed using expected-to-observed (E/O) ratio and the area under the curve (AUC) statistics. E/O ratio >1 indicates that the model predicts more lung cancer cases than observed. PLCOM2012 model was the most predictive of lung cancer for ever-smokers in I-ELCAP with the AUC 0.61 being the highest, followed by Bach model (AUC 0.58), LLPi model (AUC 0.57) and Pittsburgh Predictor (AUC 0.52). E/O ratios suggested that the PLCOM2012 model, Bach model, LLPi model and Pittsburgh Predictor model tends to overestimate the number of lung cancers. The LLPi model overestimated as many as 4 times more lung cancer cases. Using data from I-ELCAP, the four existing lung cancer risk prediction models have AUCs ranged between 0.52-0.61, PLCOM2012 model was the top performer out of the four models.

MS12.04 The International Lung Cancer Consortium (ILCCO), an International Study to Identify Risk Factors for Lung Cancer Development

The International Lung Cancer Consortium (ILCCO) was established in 2004 to maximize research efficiency for lung cancer and to share comparable epidemiological and clinical data, and biological samples across studies. Since its establishment, over 70 studies have participated in the ILCCO and shared comparable clinico-epidemiological data and a subset with biological samples and genomic data. The data harmonization was conducted at the Sinai Health System in Toronto, and genomic data is managed at the Dartmouth College of Medicine/Baylor College of Medicine. In total, the ILCCO Data Repository now has epidemiological data for over 1.2 million study participants, including 100,000 lung cancer patients, and genomic data on approximately 50,000 study participants. The large-scale epidemiological and genomic data allow us to extensively study and characterize the etiological factors, including lifestyle risk factors, medical history and genomic architectures for lung cancer development. Data submitted from all studies are systematically checked for missing values, outliers, inadmissible values, aberrant distributions and internal inconsistencies before harmonization. Common variable definitions were developed. For lifestyle risk factors and medical history, we conducted meta-analysis based on study-specific estimates, when applicable. If heterogeneities were present, random effects models were employed to account for the heterogeneity across studies. For subgroup of interests or when sample size is limited, pooled-analyses based on individual-level data were applied. When applicable, the non-linearity relationship was assessed. For genetic susceptibility of lung cancer, we investigated the genetic loci associated with lung cancer risk using log-additive model adjusted for population ancestry and account for multiple comparisons. To assess the causality of specific exposures and lung cancer risk, we applied Mendelian Randomization and mediation analytical approaches. To estimate 5-year lung cancer absolute risk, we incorporated risk factors, medical history and genetic factors based on age-specific lung cancer incidence and the competing risk. Based on 17 ILCCO studies (24,000 cases and 81,000 controls), we observed a robust association between lung cancer risk and emphysema and pneumonia, even among never smokers, and after long latency period. Based on 24 ILCCO studies, we quantified the association between family history of lung cancer and its risk by their smoking status and affected relative types. Based on 6 studies in UK, Canada, UK and New Zealand, we assessed the association between cannabis smoking and lung cancer risk by intensity, duration and cumulative exposures and by histological subtypes. We have recently completed a largest lung cancer genetic analysis based over 29,000 lung cancer cases and 56,000 controls. We identified 10 novel lung cancer susceptibility loci, in addition to the known regions, such as TERT/CLPTM1L, CHRNA5, MHC region, RAD52, CHEK2 and found specific associations mediated through mRNA expression. We helped to quantify the effect of specific genetic variant in nicotinic receptor gene on smoking cessation and age of onset. Using genetic instruments and Mendelian Randomization approach, we confirmed the association between lung cancer risk and long telomere length. Most recently, we investigated the association between impaired lung function and lung cancer risk based on UK Biobank and ILCCO OncoArray data, and we found that impaired lung function was associated with lung cancer risk in never smokers and particularly for adenocarcinoma, most likely through immune-mediated pathways. When combining all factors into an integrative risk model, we found that individuals with highly polygenic risk scores reached lung cancer screening threshold at younger age than those with average genetic risk background. ILCCO provides a powerful research platform for research on lung cancer. The collaborative projects based on ILCCO have contributed to the understanding of lung cancer etiology beyond tobacco smoking. As future perspectives, ILCCO has obtained clinical prognosis data for over 50,000 lung cancer patients and will also be able to investigate factors associated with lung cancer prognosis in depth. Finally, ILCCO has built close collaborations with several lung cancer low-dose computed tomography screening programs to jointly investigate the optimal strategy for risk stratification and early detection for lung cancer.

Understanding lung cancer screening behaviour using path analysis.

Understanding lung cancer screening behaviour is crucial to identifying potentially modifiable factors for future intervention. Qualititative work has explored attitudes and beliefs about lung cancer screening from the perspective of the participant, but the theoretically grounded factors that influence screening-eligible individuals to screen are unknown. We tested an explanatory framework for lung cancer screening participation from the individual's perspective. Data were collected as part of a sequential explanatory mixed methods study, the quantitative component of which is reported here. A national purposive sample of 515 screening-eligible participants in the United States was recruited using Facebook-targeted advertisement. Participants completed surveys assessing constructs of the Conceptual Model for Lung Cancer Screening Participation. Path analysis was used to assess the relationships between variables. Path analyses revealed that a clinician recommendation to screen, higher self-efficacy scores, and lower mistrust scores were directly associated with screening participation (p < 0.05). However, the link between screening behaviour and self-efficacy appeared to be fully mediated by fatalism, lung cancer fear, lung cancer family history, knowledge of lung cancer risk and screening, income, clinician recommendation, and social influence (p < 0.05). This study found that medical mistrust, self-efficacy, and clinician recommendation were significant in the decision of whether to screen for lung cancer. These findings offer insight into potentially modifiable targets most appropriate on which to intervene. This understanding is critical to design meaningful clinician- and patient-focused interventions.

Nitric Oxide Metabolites and Lung Cancer Incidence: A Matched Case-Control Study Nested in the ESTHER Cohort.

Studies suggest that nitric oxide (NO) may have a possible role in lung carcinogenesis. This study is aimed to evaluate the association of the NO metabolites, namely, nitrite and nitrate, with lung cancer incidence. We conducted a matched case-control study (n = 245 incident lung cancer cases and n = 735 controls) based on the German ESTHER cohort (n = 9,940). Controls were matched to cases on age, sex, smoking status (never/former/current smoking), and pack-years of smoking. The sum of nitrite and nitrate was measured in urine samples using a colorimetric assay and was standardized for renal function by urinary creatinine. Conditional logistic regression models, adjusted for lifestyle factors, asthma prevalence, and family history of lung cancer, were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). Among incident lung cancer cases, high nitrite/nitrate levels were statistically significantly associated with current smoking, a low BMI, and the oxidative stress biomarker 8-isoprostane levels. Nitrite/nitrate levels in the top quintile were statistically significantly associated with lung cancer incidence: the OR (95% CI) was 1.37 (1.04-1.82) for comparison with the bottom quintile. This association was unaltered after additional adjustment for 8-isoprostane levels and C-reactive protein (CRP). In conclusion, this large cohort study suggested that subjects with high urinary nitrite/nitrate concentrations had an increased risk of lung cancer and this association was independent of smoking, CRP, 8-isoprostane levels, and other established lung cancer risk factors. Further studies are needed to validate these findings and to confirm the hypothesis that pathologically high levels of NO are involved in lung cancer development.

Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial

BackgroundEstimation of the clinical probability of malignancy in patients with pulmonary nodules will facilitate early diagnosis, determine optimum patient management strategies and reduce overall costs.MethodsData from the UK Lung Cancer...

Genetic polymorphism of catechol-O-methyltransferase modulates the association of green tea consumption and lung cancer.

Tea polyphenols are strong antioxidants, which can be rapidly O-methylated by catechol-O-methyltransferase (COMT). Thus, it is possible that the genetic polymorphism of COMT can modulate the association of green tea consumption and lung cancer. Here, we designed a case-control study to evaluate the combined effect of green tea consumption and COMT genotypes on the risk of lung cancer. A total of 237 lung cancer patients and 474 healthy controls were recruited. Questionnaires were administered to obtain demographic data, smoking status, green tea consumption, fruits and vegetables intake, exposure to cooking fumes, and family history of lung cancer. Genotypes for COMT were identified by PCR. Smoking, green tea consumption, exposure to cooking fumes, and family history of lung cancer were associated with the development of lung cancer. When green tea drinkers carrying COMT HL/LL genotypes were selected as the reference group, drinkers carrying the COMT HH genotype had a higher risk for the development of lung cancer (odds ratio: 1.97, 95% confidence interval: 0.99-3.91). Among the current and ever smokers, the elevated risk for lung cancer was more apparent in green tea drinkers carrying the COMT HH genotype compared with green tea drinkers carrying COMT HL/LL genotypes (odds ratio: 5.84, 95% confidence interval: 1.75-19.45). Green tea drinkers with greater activity of the COMT genotype, whereby polyphenols are effectively excluded, will gain fewer protective benefits against lung cancer development.

Abstract 4215: Patient and screening characteristics associated with positive lung cancer screening examinations

Abstract Introduction. The likelihood of having a positive low dose computed tomography (LDCT) lung cancer screening (LCS) examination that requires workup may vary according to patients’ characteristics and risk factors. The purpose of this study is to evaluate patient characteristics associated with positive LCS exams. Methods. We utilized data from 1684 LDCT exams conducted for LCS at five academic and community sites from 2015-2018. During the screening visit, patients were asked to complete a comprehensive questionnaire including socio-demographics, smoking history, occupational and environmental exposures, family history of lung cancer, and comorbid conditions. Information on the LCS examination, including the radiologists’ Lung Reporting and Data System (Lung-RADS) assessment, was obtained from the radiologist report. We dichotomized Lung-RADS into negative (Lung-RADS 1 (negative) or 2 (benign appearance or behavior)) and positive (Lung-RADS 3 (probably benign), 4A (suspicious), or 4B (suspicious)) based on the management recommendation of continuing with annual screening in 12 months or requiring follow-up before 12 months. We compared Lung-RADS results (positive versus negative) by patient characteristics using chi-square tests and examined predictors of positive LCS exams using multivariate logistic regression, reporting adjusted odds ratios (aORs) and 95% confidence intervals (95%CI). Results. Screened patients ranged in age from 50-78 years, with 46.7% less than 65 years and 53.3% ages 65 or older. Approximately 53.3% were male and 46.7% were female; 84.5% were White, 11.8% were African American, and 3.7% were other races. The majority (76.5%) of screened patients were overweight or obese. Two-thirds (68.5%) of patients had more than one LCS exam. Most (85.0%) LCS exams were negative while 15.0% were positive. There were no significant differences in Lung-RADS assessment by race, gender, education, or body mass index. Lung-RADS were significantly more likely to be positive in those ages 65 and older versus those ages less than 65 (aOR=1.47, 95%CI: 1.03-2.10) and in baseline versus subsequent screening exams (aOR=0.43, 95%CI: 0.30-0.62). Conclusion. Predictors of having a positive LCS exam requiring work-up before the next recommended annual screening test include being aged 65 and older and having a baseline LCS examination. Citation Format: Louise M. Henderson, Samantha Sites, Tina Tailor, Sara C. Bearden, Roger Huamani, Allison Throneburg, Max Nagle, M Patricia Rivera. Patient and screening characteristics associated with positive lung cancer screening examinations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4215.

Familial association of lung cancer with liver cancer in first-degree relatives.

Purpose: Besides the smoking and occupational exposures, heritable factors have been proven to be a risk factor for lung cancer by several population-based studies, which would misestimate the risk of lung cancer.Patients and methods: To quantify the magnitude of the high risk of lung cancer with family history, we performed a case-based study with 1373 enrolled individuals, which may be more accurate than a population-based study.Results: Risk of lung cancer was higher in people with lung cancer family history than in the control group (OR 2.50, p<0.001). Individuals with family history of liver cancer also had a higher risk of lung cancer than the control group (OR 1.78, p=0.038) while there was no significant difference within the individuals with family history of colorectal cancer, esophageal cancer, nasopharyngeal cancer or breast cancer. Furthermore, the risk of lung cancer in the subjects with early-onset cancers (age <50 years) was higher than the later-onset cancers (age ≥50 years), especially in individuals with family history of liver cancer (OR 9.24 vs 1.39). Risk of lung cancer in females with family history of lung cancer or liver cancer was higher than in males.Conclusion: The results of this study proved that the familial aggregation of lung cancer and liver cancer manifests higher risks of lung cancer, supporting the hypothesis that lung cancer and liver cancer are attributable to common familial predisposition.

Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer

IntroductionPublished risk estimates for diagnosis of lung cancer based on family history are typically focused on close relatives, rather than a more diverse or complete family history. This study provides estimates of relative risk (RR) for lung cancer based on comprehensive family history data obtained from a statewide cancer registry linked to a high-quality genealogy data resource that is extensive and deep. The risk estimates presented avoid common recall, recruitment, ascertainment biases, and are based on an individual’s (proband’s) lung cancer family history constellation (pattern of lung cancer affected relatives); numerous constellations are explored. MethodsWe used a population-based genealogic resource linked to a statewide electronic Surveillance Epidemiology and End Results program cancer registry to estimate RR for lung cancer for an individual based on their lung cancer family history. The family history data available for a proband included degree of relationship (first- to third-degree), paternal or maternal family lung cancer history, number of lung cancer–affected relatives, and age at diagnosis of affected relatives. More than 1.3 million probands with specific constellations of lung cancer were analyzed. To estimate RRs for lung cancer, the observed number of lung cancer cases among probands with a specific family history constellation was compared to the expected number using internal cohort-specific rates. ResultsA total of 5048 lung cancer cases were identified. Significantly elevated RR was observed for any number of lung cancer–affected relatives among first-, second-, or third-degree relatives. RRs for lung cancer were significantly elevated for each additional lung cancer first-degree relative (FDR) ranging from RR = 2.57 (confidence interval [CI] 95%: 2.39, 2.76) for 1 or more FDR to RR = 4.24 (CI 95%: 1.56, 9.23) for 3 or more FDRs affected. In an absence of FDR family history, increased risk for lung cancer was significant for increasing numbers of affected second-degree relatives (SDRs) ranging from 1.41 (CI 95%: 1.30, 1.52) for 1 or more SDRs to 4.76 (CI 95%: 1.55, 11.11) for 4 or more SDRs. In the absence of affected FDRs and SDRs, there were significantly increased risks based on lung cancer–affected third-degree relatives (TDRs) ranging from 1.18 (CI 95%: 1.11, 1.24) for 1 or more affected TDRs to 1.55 (CI 95%: 1.03, 2.24) for 4 or more affected TDRs. RRs were significantly increased with earlier age at diagnosis of a FDR, and equivalent risks for maternal compared to paternal history were observed. ConclusionsThis study provides population-based estimates of lung cancer risk based on a proband’s complete family history (lung cancer constellation). Many individuals at two to five or more times increased risk for lung cancer are identified. Estimates of RR for lung cancer based on family history are arguably relevant clinically. The constellation RR estimates presented could serve in individual decision-making to direct resource use for lung cancer screening, and could be pivotal in decision-making for screening, treatment, and post-treatment surveillance.

Paraneoplastic Lambert-Eaton syndrome in a patient with disseminated metastatic cancer.

Neurological paraneoplastic syndromes are rare, occur in 0.01% of all cancer patients; like part of them, the Lambert-Eaton syndrome is an autoimmune presynaptic disorder of neuromuscular transmission characterized by muscle weakness and neurovegetative dysfunction, and often associated with small cell lung cancer. A 72 years old female with a family history of lung cancer and leukemia, with 7 months of dry cough and 3 months with waist and pelvic muscle weakness, oropharyngeal dysphagia, dry mouth, chronic constipation and weight loss of 10 kg. Physical examination: patient prostrated; clinical muscle examination: pelvic muscles waist -3/5 and -4/5 the rest; diminished reflexes. Laboratory normal parathormone and hypercalcemia. With electrophysiological study and positive anti-voltage-gated calcium channel antibodies, confirming Lambert-Eaton syndrome and imaging studies with neoplastic condition in brain, liver and kidney, with unspecified primary origin.

Tobacco Smoking Modifies the Association between Hormonal Factors and Lung Cancer Occurrence among Post-Menopausal Chinese Women

Inconsistent evidence has been reported on the role of female hormonal factors in the development of lung cancer. This population-based case–control study evaluated the main effect of menstrual/reproductive factors on the risk of lung cancer, and the effect modification by smoking status. Multivariable unconditional logistic regression models were applied adjusted for age, income, education, county of residence, body mass index, smoking status, pack-years of smoking, and family history of lung cancer. Among 680 lung cancer cases and 1,808 controls, later menopause (at >54 vs. <46 years old) was associated with increased risk of lung cancer (SBOR, semi-Bayes adjusted odds ratio = 1.61, 95% PI, posterior interval = 1.10–2.36). More pregnancies (2 or 3 vs. 0 or 1) was associated with decreased risk (SBOR = 0.71, 95% PI = 0.53, 0.95). Ever being a smoker and having two or fewer pregnancies in one's lifetime could jointly increase the odds of lung cancer (RERI, relative excess risk due to interaction = 1.71, 95% CI = 0.03, 3.38). An increased number of ovulatory cycles was associated with increased risk of lung cancer (SBOR for 13 ovulatory cycles = 1.02, 95% CI = 1.00+, 1.04).

Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non-small cell lung cancer.

BackgroundBoth genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non‐tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied.MethodsWe selected 410 non‐small cell lung cancer (NSCLC) patients with a family history of lung cancer (FLC) and exposure to coal combustion between 2014 and 2017. Clinicopathologic parameters were analyzed. Reverse transcription‐PCR was performed to detect ALK, ROS1, RET, and NTRK1 rearrangement.ResultsAmong the 410 NSCLC patients, 192 had FLC and 204 (49.8%) were exposed to occupational or domestic coal combustion. FLC patients had the same characteristics regardless of gender and coal exposure: younger age, high female ratio, adenocarcinoma, increased metastasis, later stage at diagnosis, and higher frequency of gene fusion. Sixty‐seven patients (16.3%) had gene rearrangement: 51 (12.4%) harbored EML4‐ALK fusions and 16 ROS1 fusions (3.9%). The highest gene fusion rate (35.1%, 33/94) occurred in patients with both FLC and high tobacco and coal exposure. ALK fusions and total gene rearrangement were closely associated with women, never smokers, younger age, FLC, and coal exposure.ConclusionFLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer.

Abstract P5-09-12: Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing

Abstract Background: Li-Fraumeni syndrome (LFS) is a rare autosomal genetic disorder with germline TP53 mutations. Patients with TP53 mutations have a higher risk of developing breast cancer than those harboring BRCA mutations. Although limited studies have shown that TP53 mutation carriers are less responsive to low dose radiation and more susceptible to induce new malignancies from radiotherapy. Moreover screening strategies allows early detection of a spectrum of cancers related to TP53 mutations. From work of BRCA mutations where over 40% novel mutations were detected in Chinese cohort, it is important to evaluate the frequency of TP53 mutation in Chinese to better understand the spectrum to guide appropriate clinical management of these high risk individuals. Methods: TP53 gene mutation screening was performed on 2,561 high-risk breast cancer patients using multigene panel testing. The patients were accrued by Hong Kong Hereditary and High Risk Breast Cancer Program from March 2007 to May 2018. All detected pathogenic mutations were further validated by bi-directional DNA sequencing and analyzed by our in-house developed bioinformatics pipeline. Results: Sixteen distinct pathogenic or likely pathogenic variants were identified, and 3 of them were de novo TP53 mutations (18.75%). The mean age of patients who harbored TP53 mutation was 30.44 years (range 18-44), and 50% of the tumors were bilateral breast cancer. Of sixteen different pathogenic mutations, majority of them were missense mutation (87.5%), and 2 were nonsense mutation (12.5%). Four of the sixteen TP53 mutation carriers had family history of breast cancer, while others had a family history of lung cancer (43.75%). Conclusion: This study revealed that seven patients were found to habor TP53 mutation even when they did not meet the criteria of LFS of LFS-like phenotype, implicated the importance of using multigene panel test for probands and their relatives to offer a comprehensive surveillance programe for TP53 carriers. Citation Format: Kwong A, Shin V, Au CH, Ho C, Slavin T, Weitzel J, Chan TL, Ma E. Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-12.

Association between Family History of Cancer and Lung Cancer Risk among Japanese Men and Women.

Although cigarette smoking is a major risk factor for lung cancer, genetic susceptibility may also affect lung cancer risk. To explore the role of genetic risk, this case-control study investigated the association between family history of cancer at several sites and lung cancer risk. A total of 1,733 lung cancer cases and 6,643 controls were selected from patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2009. Information on family history of cancer was collected using a self-administered questionnaire and odds ratios (ORs) were estimated by unconditional logistic regression. Family history of lung cancer in first-degree relatives was associated with an increased risk of lung cancer among both sexes. According to histology and type of relatives, a parental history of lung cancer was significantly associated with an increased risk of female adenocarcinoma (OR = 1.72). Stratification by smoking status revealed that this significant positive association in women was limited to ever-smokers (OR = 4.13). In men, a history of lung cancer in siblings was significantly associated with an increased risk of small cell carcinoma (OR = 2.28) and adenocarcinoma (OR = 2.25). Otherwise, positive associations between history of breast (OR = 1.99) and total (OR = 1.71) cancers in siblings and the risk of male adenocarcinoma were observed. These results suggest that inherited genetic susceptibility may contribute to the development of lung cancer. In men, shared exposure to environmental factors among siblings may also be responsible for the increase in lung cancer risk.