Family History Of Esophageal Cancer Research Articles

Primary esophageal melanoma with a family history of esophageal cancer

A rare clinical observation of a 46-year-old patient with primary esophageal melanoma is presented. We demonstrate the difficulties of verifying the disease, taking into account the complex morphological picture of the tumor, anatomical features. The possibilities of modern combined treatment of this category of patients are also shown. For the first time, a case of primary esophageal melanoma with a family history of esophageal cancer is described.

Family history of cancer is a prognostic factor for better survival in operable esophageal squamous cell carcinoma: A propensity score matching analysis.

Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. A family history of cancer is a favorable independent prognostic factor in ESCC. Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. A family history of cancer (FH) is closely associated with the risk and survival of many cancers. However, the effect of FH on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. We performed a large cohort study in the Chinese population to obtain insight into the prognostic value of FH in patients with operable ESCC. A total of 1,322 consecutive patients with thoracic ESCC who had undergone esophagectomy between January 1997 and December 2013 were included. The FH group included patients with any degree of FH, while the non-FH group included patients without any degree of FH. In total, 215 patients with FH and 215 without FH were matched using the propensity score matching analysis method to adjust for differences in baseline variables between the two groups. The impact of FH on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox's proportional hazards models. Before matching, 280 (21.2%) patients were included in the FH group and 1,042 (78.8%) in the non-FH group. FH was associated with early pathological T stage (p = 0.001), lymph node-negative status (p = 0.022), and early pathological stage (p = 0.006). After matching, FH was an independent prognostic factor for DFS and OS in ESCC patients. Patients with FH had 35% lower risk of disease progression (hazard ratio [HR] = 0.65, 95% CI: 0.51-0.84, p = 0.001) and 34% lower risk of death (HR = 0.66, 95% CI: 0.51-0.86, p = 0.002) than those without FH. Patients with a family history of digestive tract cancer (FH-DC), a family history of esophageal cancer (FH-EC), FH in first-degree relatives (FH-FD), and more than one relative affected by cancer were associated with favorable DFS and OS as compared to those without FH. FH is a favorable independent prognostic factor in ESCC. Patients with FH, especially those with FH-DC, FH-EC, FH-FD, and more than one relative affected by cancer, had improved survival.

Association of GSTP1 and PLCE1 gene polymorphisms with primary esophageal cancer

To assess the association of polymorphisms of glutathione S-transferase P1 (GSTP1) and phospholipase C epsilon-1 (PLCE1) genes with the susceptibility of primary esophageal cancer and their interaction with environmental factors. 162 patients with primary esophageal cancer and 162 healthy controls were recruited in this cross-sectional study. Basic information such as gender, age, history of smoking and alcohol consumption and family history of esophageal cancer were collected. Single nucleotide polymorphisms at A105G locus of GSTP1 gene and rs3765524, rs2274223 and rs3781264 loci of PLCE1 gene were detected. A logistic regression model was established to analyze the risk factors of esophageal cancer and the interaction among the factors. The proportions of individuals with smoking history, family history of esophageal cancer and hot diet in esophageal cancer group were higher than those in the control group (P<0.05). Conditional Logistic regression analysis showed that smoking, family history of esophageal cancer and GG genotype at the rs2274223 locus of PLCE1 gene were the risk factors for esophageal cancer (P<0.05), and AG/GG genotypes at the A105G locus of GSTP1 gene were the protective factors for esophageal cancer (P<0.05). In the two-factor interaction model, both AA genotype at A105G locus of GSTP1 gene and GG genotype at rs2274223 locus of PLCE1 gene had an interaction with smoking, and the risk of esophageal cancer has increased by 83.6% and 85.7%, respectively (P<0.05). AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene and smoking constituted the best three-factor interaction model, and the risk of esophageal cancer has increased by 244.0% (P<0.05). Four-factor interaction model analysis showed that the risk of esophageal cancer among individuals with AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene, smoking and family history of esophageal cancer has increased by 264.4% (P<0.05). The AG and GG genotypes at the A105G locus of GSTP1 gene are protective factors for esophageal cancer, and the GG genotype at rs2274223 locus of PLCE1 gene is a risk factor, both of them may interact with smoking and affect the susceptibility to esophageal cancer.

Risk factors associated with esophageal cancers, diagnosed at tertiary level in Afghanistan: a descriptive cross-sectional study

Background:Worldwide, esophageal cancer (EC) is a common cancer in term of incidence and mortality and is the 4th common cancer in Afghanistan. Current study aimed to evaluate the profile of risk factors for EC among patients diagnosed at tertiary level in Afghanistan.Methodology:A descriptive cross-sectional study was carried out between January 2019 up to February 2021 including all esophageal cancers diagnosed at pathology department of French Medical Institute for Mothers and Children, Afghanistan.Result:240 diagnosed cases were analyzed, in which 59.40% of squamous cell carcinoma and 41.07% Adenocarcinoma. Both histopathological type of were predominantly diagnosed in males. The majority of the patients were residents of rural areas. More than 80% of the patients were illiterate with only less than 2% completing higher education. Majority of the patients were laborers and farmers while less than 10% were employed. According to income assessment, more than 80% were from low-income household, the rest from middle-income and none from high-income family. Oral snuff consumption was noted in 33.9% of squamous cell carcinoma patients and 40% adenocarcinoma patients whereas, family history of esophageal cancer was observed in 37.8% and 36.7% in both types of carcinomas, respectively. More than 60% of both types of carcinomas patients were hot tea drinkers.Conclusion:Current study demonstrated that most patients diagnosed with esophageal cancers were male, uneducated, belongs to low-income groups, lives in rural areas. These findings suggest distribution of esophageal cancer in specific socioeconomic groups, clearly demonstrating the need further analytical study.

Risk Factors Related to Esophageal Cancer, a Case-Control Study in Herat Province of Afghanistan.

The Herat province of Afghanistan is located on the Asian Esophageal Cancer Belt (AECB), a wide area in Central and Eastern Asia where very high rates of esophageal cancer (EC) have been observed. Several risk factors have been reported in the AECB Region by previous studies. Considering lack of information in Afghanistan on this issue, a study was conducted to determine the major risk factors related to EC in order to guide protective measures. A population-based case-control study was performed from July 2015 to August 2016 among 657 EC patients in the Herat Province and 180 histopathological confirmed cases and 189 controls were interviewed. A structured questionnaire was used and face-to-face interviews were conducted. Low body mass index (BMI), low socio-economic status, family history of EC, consumption of dark tea, very hot beverage and qulurtoroosh were found to be statistically significant for EC and esophageal squamous cell carcinoma (ESCC) in univariate analyses. According to multivariate analyses, sex (OR=2.268; 95% CI=1.238-4.153), very hot beverages (OR=2.253; 95% CI=1.271- 3.996), qulurtoroosh (OR=5.679; 95% CI=1.787-18.815), dark tea (OR=2.757; 95% CI=1.531-4.967), high previous BMI (OR=0.215; 95% CI=0.117-0.431) and low socio-economic status (OR=1.783; 95% CI=1.007-3.177) were associated with ESCC. Being male was found to increase the risk of ESCC with OR=2.268 (95% CI=1.238-4.153). Consuming very hot beverages dark tea and a local food, qulurtoroosh, were found as important risk factors for EC. Our findings warrant further studies and necessitate the implementation of protective measures for EC which is one of the leading cancers in the region.

Contribution of germline PALB2 variants to an unselected and prospectively registered pancreatic cancer patient cohort in Pakistan

BackgroundPartner and localizer of BRCA2 (PALB2) is a pancreatic cancer (PC) susceptibility gene reported in Caucasians. However, limited data are available among Asians. We investigated the contribution of PALB2 germline variants to Pakistani PC patients. Methods150 unselected and prospectively enrolled PC patients were comprehensively screened for PALB2 variants, using denaturing high-performance liquid chromatography and DNA sequencing. Novel variants were investigated for their pathogenic effect using in-silico tools. Potentially functional variants were screened in 200 controls. ResultsTwenty-two different PALB2 variants were identified. A missense variant (p.Arg37His) was identified in a 48-years-old male patient with a family history of breast cancer. Another missense variant (p.Trp898Arg) was identified in a 48-years-old male patient with a family history of esophageal cancer. A novel 3′ downstream variant (c.∗480A>G) was detected in a 34-years-old female patient with family history of lung cancer. Another novel 3′ downstream variant (c.∗417A>C) was identified in a 41-years-old male patient. All these variants were absent in 200 controls. p.Arg37His and p.Trp898Arg were predicted as likely pathogenic. c.∗417A>C and c.∗480A>G were classified as variants of uncertain significance. ConclusionThis is the first study that suggests a minimal contribution of PALB2 variants to PC risk in Pakistani population.

Endoscopic Surveillance for Premalignant Esophageal Lesions: A Community-Based Multicenter, Prospective Cohort Study

Mild and moderate dysplasia are major premalignant lesions of esophageal squamous cell carcinoma (ESCC); however, evidence of the progression risk in patients with these conditions is extremely limited. We aimed to assess the incidence and risk factors for advanced neoplasia in patients with mild-moderate dysplasia. This prospective cohort study included patients with mild-moderate dysplasia from 9 regions in rural China. These patients were identified from a community-based ESCC screening program conducted between 2010 and 2016 and were offered endoscopic surveillance until December 2021. We estimated the incidence of advanced esophageal neoplasia, including severe dysplasia, carcinoma in situ, or ESCC, and identified potential risk factors using the Cox regression model. The 1183 patients with mild-moderate dysplasia were followed up over a period of 6.95 years. During follow-up evaluation, 88 patients progressed to advanced neoplasia (7.44%), with an incidence rate of 10.44 per 1000 person-years. The median interval from the progression of mild-moderate dysplasia to advanced neoplasia was 2.39 years (interquartile range, 1.58-4.32y). A total of 74.47% of patients with mild-moderate dysplasia experienced regression tonondysplasia, and 18.09% showed no lesion progression. Patients with mild-moderate dysplasia who had a family history of esophageal cancer and were age 55 years and oldershowed 97% higher advanced neoplasia yields than all patients with mild-moderate dysplasia. In a country with a high incidence of ESCC, patients with mild-moderate dysplasia showed an overall risk of advanced neoplasia progression of 1.04% per year. Patients with mild-moderate dysplasia would be recommended for endoscopic surveillance during the first 2 to 3 years.

Prevalence of esophageal squamous dysplasia in relatives of patients with esophageal cancer in Southwestern Kenya

BackgroundEsophageal squamous cell carcinoma (ESCC) and its asymptomatic precursor lesion, esophageal squamous dysplasia (ESD), are common in East Africa. It is unknown whether family history of esophageal cancer is a risk factor for both ESD and ESCC in Africa, and whether family members of affected persons should be screened. MethodsWe recruited 296 asymptomatic adult first-degree relatives of ESCC patients residing in southwestern Kenya. Participants completed questionnaires and underwent endoscopy with Lugol’s iodine staining and biopsy to determine the prevalence of ESD. Prevalence comparisons were made with a prior population-based cohort from the same catchment area who also underwent Lugol’s chromoendoscopy. ResultsMean age was 40.7 years, compared to 62.7 years in the prior population study. The overall prevalence of ESD/ESCC among first-degree relatives was 14.7%, comparable to the background population prevalence of 14.4%, and this comparability remained even after adjusting for the different age distributions of the studies. Post-primary education was the only measured variable that was associated with a decreased risk of ESD/ESCC (adjusted OR=0.31, 95% CI: 0.11, 0.83). There was heterogeneity in the ESD prevalence across families, even after adjustments for varying age and other measured factors. ConclusionsThe prevalence of esophageal squamous dysplasia among first-degree relatives of persons with ESCC was similar to that of the background population of southwestern Kenya; however, there was heterogeneity in ESD prevalence between families, suggesting other genetic or environmental factors may influence family prevalence. Further study of families with a high prevalence of ESD or ESCC is justified.

Risk factors for precancerous lesions of esophageal squamous cell carcinoma in high-risk areas of rural China: A population-based screening study.

Although many studies in China have found that environmental or lifestyle factors are major contributors to the etiology of esophageal cancer, most of the patients in the above studies are in the middle and late stages, the early-stage patients account for a small proportion. To clarify the risk/protective factors contributing to early lesions, we conducted the present cross-sectional study.A total of 2925 healthy controls and 402 patients with esophageal precancerous lesions were included in our study by endoscopic examination. Information on risk/protective factors was collected by personal interview, and unconditional logistic regression was used to determine adjusted odds ratios (AORs) by the maximum-likelihood method.Smoking >20 pack-years (AOR = 1.48), duration of drinking >30 years (AOR = 1.40), alcohol consumption >100 mL/d (AOR = 1.44), gastroesophageal reflux disease (AOR = 1.75), esophagitis (AOR = 1.25), a family history of esophageal cancer (AOR = 1.92), or stomach cancer (AOR = 1.92) were significant risk factors for esophageal precancerous lesions. There was a negative correlation between abdominal obesity and early esophageal cancer and precancerous lesions (AOR = 0.75). In addition, we found that there was a synergistic effect between a family history of esophageal cancer and drinking (AOR = 3.00) and smoking (AOR = 2.90).Lifestyle risk factors, genetic factors, and upper gastrointestinal diseases are associated with the development of esophageal precancerous lesions. These results highlight the need for primary prevention to reduce the future burden of cancer and other chronic diseases in high-risk areas of rural China.

Family History of Colorectal or Esophageal Cancer in Barrett's Esophagus and Potentially Explanatory Genetic Variants.

INTRODUCTION:We aimed to estimate the effects of a family history of colorectal cancer (CRC) or esophageal cancer on the risk of Barrett's esophagus (BE) and identify variants in cancer genes that may explain the association.METHODS:Men scheduled for screening colonoscopy were recruited to undergo upper endoscopy. Cases and noncases were screenees with and without BE, respectively. The effects of family histories on BE were estimated with logistic regression, adjusting for the potential confounders. We additionally recruited men recently diagnosed with BE by clinically indicated endoscopies. Banked germline DNA from cases of BE with ≥2 first-degree relatives (FDRs) with CRC and/or an FDR with esophageal cancer underwent next-generation sequencing using a panel of 275 cancer genes.RESULTS:Of the 822 men screened for CRC who underwent upper endoscopy, 70 were newly diagnosed with BE (8.5%). BE was associated with family histories of esophageal cancer (odds ratio = 2.63; 95% confidence interval = 1.07–6.47) and CRC in ≥2 vs 0 FDRs (odds ratio = 3.73; 95% confidence interval = 0.898–15.4). DNA analysis of subjects with both BE and a family history of cancer identified one or more germline variants of interest in genes associated with cancer predisposition in 10 of 14 subjects, including the same novel variant in EPHA5 in 2 unrelated individuals.DISCUSSION:We found an increased risk for BE associated with a family history of esophageal cancer or CRC. Although analysis of germline DNA yielded no clinically actionable findings, discovery of the same EPHA5 variant of uncertain significance in 2 of 14 cases merits additional investigation.

Family history (FH) of gastrointestinal (GI) cancer and behavioral risks: Analysis of an Internet-based risk assessment tool.

807 Background: Certain behaviors are known modifiable risk factors for development of GI cancers. The relationship between family history (FH) of GI cancers and individuals’ behaviors is not well understood, but is important for risk assessment/ counseling. Methods: The OncoLink “Reduce My Risk” tool is a publicly available online survey created in 2009 to provide customized information regarding cancer risk. Details of this survey have been reported; research is IRB-approved. Differences between those with v. without FH of GI cancers were analyzed using chi-square test. Results: 28,001 surveys were submitted. Median age was 26y (18-101), 60% female, 87% lived in North America, 76% White/Non-Hispanic, 64% reported FH of cancer. Individuals with FH of CRC reported eating less red meat (31% v. 34%, p = 0.007), processed grains (55% v. 59%, p &lt; 0.001), or charred meats (14% v. 19%, p &lt; 0.001), but were equally likely to be vegetarian (9% v. 10%, p = 0.059). Those with FH of esophageal cancer were more likely to have GERD (16% v. 9%), smoke &gt; = 1 pack per day (7% vs. 4%) and drink alcohol (63% v. 55%) (p &lt; 0.001 for all). Those with FH of gastric cancer were more likely to have H. Pylori or gastric ulcers (5% v. 3%, p &lt; 0.001), but no difference in the consumption of smoked/salted foods (27% v. 25%, p = 0.20). Those with FH of HCC reported no differences in alcohol consumption (56% v. 55%, p = 0.41) or hepatitis B virus (HBV) vaccination (62% v. 62%, p = 0.66). Those with FH of anal cancer were more likely to have receptive anal intercourse (26% v. 16%, p &lt; 0.001) but showed no differences in human papillomavirus (HPV) vaccination (21% v. 22%, p = 0.91). Those with FH of HCC (15% v. 13%, p = 0.035), gastric (16% v. 13%, p = 0.001), esophageal (17% v. 13%, p &lt; 0.001), and anal (21% vs. 13%, p &lt; 0.001) cancers were more likely to be smokers; those with a FH of CRC were less likely (11% v. 13%, p = 0.006), and those with FH of pancreatic (12% vs. 13%, p = 0.71) or cholangiocarcinoma (15% vs. 13%, p = 0.59) showed no difference. Conclusions: Many individuals with a FH of GI cancers engage in behavioral and other modifiable risk factors that increase risk for GI and other cancers. Future work should explore utility of targeted intervention and screening.

Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China: A nested case-control study.

ObjectiveWe aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.MethodsWe conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China. The oral microbiome was evaluated with 16S ribosomal RNA (rRNA) gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above (SDA) and 168 matched healthy controls. DESeq analysis was performed to identify taxa of differential abundance. Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.ResultsA total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls (all P<0.05 & false discovery rate-adjusted Q<0.10). A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve (AUC) of 0.89 (95% CI, 0.84−0.93). Cross-validation and sensitivity analysis, excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls, or restriction to screen-endoscopic-detected or clinically diagnosed case-control triads, or using only bacterial data measured at the baseline, yielded AUCs>0.84.ConclusionsThe oral microbiome may play an etiological and predictive role in esophageal cancer, and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

Differential Cumulative Risk of Genetic Polymorphisms in Familial and Nonfamilial Esophageal Squamous Cell Carcinoma.

To explore the relationship between family history of esophageal cancer, SNPs, and the risk of esophageal squamous cell carcinoma (ESCC), we performed a population-based case-control study and developed a genetic family history-related risk (GFR) score and non-family history-related risk (GnFR) score to quantify the cumulative number of risk genotypes carried by each individual. We used data of 700 patients with nonfamilial ESCC, 341 patients with familial ESCC, 1,445 controls without a family history of esophageal cancer, and 319 controls with a family history. We genotyped 87 genetic variants associated with the risk for ESCC, and constructed GFR and GnFR scores for cases and controls. Our results show that ESCC risk increased with higher GFR score (P trend = 0.0096). Among the familial subgroup, we observed a nearly 7-fold [95% confidence interval (CI), 1.92-24.77] higher risk of ESCC in the highest GFR score group. The corresponding estimate was only 2-fold (95% CI, 1.41-3.93) higher risk of ESCC, in the stratum without a reported family history of esophageal cancer. Certain cell signaling pathways and immune-related pathways were enriched, specifically in familial ESCC. Results from a reconstructed cohort analysis demonstrated that cumulative risk to get esophageal cancer by age 75 years was 13.3%, 10.2%, 8.2%, and 5.1%, respectively, in four subgroups as defined by first-degree relatives of cases or controls with high or low genetic risk score. In particular, the cohort of relatives of ESCC cases with low genetic risk score exhibit a higher cumulative risk than the cohort of relatives of controls with high genetic risk score. It demonstrates that environmental factors play a major role in esophageal cancer. Further studies are warranted to dissect the mechanisms of shared environmental and genetic susceptibility affecting the risk of getting ESCC. Our study highlights that the need of preventive strategies to screen certain genetic polymorphisms, especially in individuals whose relatives had ESCC.

A Case of Palmoplantar Hyperkeratosis and Strong Family History of Esophageal Cancer: Tylosis or Not?

A Case of Palmoplantar Hyperkeratosis and Strong Family History of Esophageal Cancer: Tylosis or Not?

Correlation between Histopathological Findings and Endoscopy in Esophageal Cance: Results in Khorramabad, Iran, Western Iran

Background: Esophageal cancer is a cancer arising of the esophagus and during the past two decades, the epidemiology and treatment strategies for esophageal cancer have changed markedly in the Western Iran.The aim of this study is to investigate the clinical signs, endoscopy findings, and family history of esophageal cancer in the Khorramabad, Iran.Methods: In this cross-sectional research conducted during 1 year in 2015,96 patients had been diagnosed with esophageal cancer by endoscopy and pathological findings. The data collected through a multipart questionnaire includingage, sex, marital status, education, occupation, address and ethnicity, background as to smoking, alcohol consumption and history of gastric and esophageal cancers. The data were analyzed using chi-square test or Fisher exact test.Results: According to findings of this study, the most common clinical signs in the patients were Anorexia (53.1) and Weight Loss (62.5). The most common anatomical site of tumor in male was in the distal esophagus (41.3%) and middle esophagus in female patients (32%), which was statistically significant (P=0.047).Conclusions: In this study, distal esophageal cancer was more common. Abetter identification of Effective factors on esophageal cancer would result in better control and management of this disease.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.619-624

Factors Associated With Early-Onset Esophageal Cancer in Tanzania: A Case-Control Study

Abstract 89 Purpose Previous studies have characterized geographic clusters of esophageal cancer (EC) in East Africa. Many of the epidemiologic features of EC in this context are shared globally with other clusters, including high rates, male predominance, and squamous cell histology. A unique feature in East Africa is the high proportion of young patients, with a recent case series reporting up to 24% of patients age &lt; 45 years. The aim of the current study was to assess factors that are associated with early-onset EC in Tanzania (TZ). Methods We performed a secondary analysis of a previous case-control study. Patients with newly diagnosed EC were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute in 2014 to 2016. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for gender and age ± 10 years. Risk factors were assessed through interviews. Logistic regression was used to estimate age-specific odds ratios (ORs) of EC for exposures across age groups (30 to 44 years, 45 to 59 years, and ≥ 60 years) and for interactions with age. Results A total of 473 cases and 473 controls were enrolled. Median ages were 59 years (range, 30 to 91 years) for cases and 55 years (range, 31 to 88 years) for controls. Among cases, 102 patients (22%) were age 30 to 44 years, 144 patients (30%) were age 45 to 59 years, and 227 patients (48%) were age ≥ 60 years. High household income was protective for those age 30 to 44 years (OR, 0.08; 95% CI, 0.01 to 0.69) and 45 to 59 years (OR, 0.13; 95% CI, 0.04 to 0.45), but not for those age ≥ 60 years (effect modification P = .047). Family history of EC was associated with a higher risk of EC among those age 45 to 59 years (OR, 3.8; 95% CI, 1.02 to 14.47) and age ≥ 60 years (OR, 6.63; 95% CI, 1.50 to 29.37), with no effect among those age 30 to 44 years (effect modification P = .019). Second-hand smoke and infrequent teeth cleaning were also associated with early-onset EC, but did not differ significantly across age groups. Additional factors associated with EC risk across all ages were firewood use (cooking), kerosene use (lighting), work on a maize farm, and in-home grain and nut storage. Protective factors were the regular use of medication, surrogates of high socioeconomic status (TV, radio, refrigerator, indoor toilet, and electricity), and charcoal or gas cooking. Conclusion Multiple exposures were identified as risk factors for early-onset EC in TZ. In age-stratified analyses, household income, second-hand smoke, and poor dental hygiene emerged as possible risk factors, whereas family history of EC had strong associations among the older but not the young age group. Our results suggest that environmental factors may underlie the high incidence of young patients with EC in TZ. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.

Abstract 2706: KRT16 germline mutation associated with familial syndrome of tylosis with esophageal cancer (TOC)

Abstract Tylosis (palmoplantar keratoderma) with esophageal cancer (TOC) also known as Howel-Evans syndrome has been associated with pathogenic mutations in RHBDF2. A potential TOC family was referred for clinical evaluation at the Family Cancer Assessment Clinic (FCAC) at Huntsman Cancer Institute, Salt Lake City, Utah. Multiple relatives of the proband had hyperkeratosis on the areas of skin associated with pressure and friction, especially the feet, as well as oral leukoplakia. The proband’s father, paternal aunt, paternal grandfather, and paternal great grandfather had been diagnosed with esophageal cancer. Clinical testing was unable to identify a germline mutation in RHBDFR2 that explained the observed phenotype and inheritance pattern. As part of Heritage 1K Project (University of Utah), Pediatric &amp; Adult Cancer Section, we performed whole genome sequencing (WGS) on 5 family members, 4 that were affected with the hyperkeratosis, and 1 unaffected family member, to identify other potential genetic causes for the observed TOC phenotype. We prioritized variants via VAAST (Variant Annotation, Analysis and Search Tool). Reducing our genes of interest to those involved in palmoplantar keratoderma with PHEVOR (Phenotype Driven Variant Ontological Re-ranking Tool), we identified a pathogenic mutation: KRT16 c.379C&amp;gt;T p.Arg127Cys. This mutation is reported in a large palmoplantar keratoderma family (without esophageal cancer) and is listed as pathogenic in Clinvar (www.ncbi.nlm.nih.gov/clinvar). KRT16 c.379C&amp;gt;T p.Arg127Cys was present in each of the affected family members, but not in the unaffected relative. Our analysis is the first of its kind to suggest carriers of pathogenic variants in KRT16 are at-risk for esophageal cancer, and may benefit from esophageal surveillance. Additionally, patients presenting with a family history of esophageal cancer should be considered for germline testing for KRT16 mutations along with RHBDF2 mutations. Citation Format: Erin L. Young, Lance Pflieger, Luke Maese, Trent Fowler, Kinley Garfield, N. Jewel Samadder, Bella Johnson, Clinton C. Mason, Barry Moore, Shawn Ryanearson, Mark Yandell, Wendy Kohlmann, Joshua D. Schiffman. KRT16 germline mutation associated with familial syndrome of tylosis with esophageal cancer (TOC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2706. doi:10.1158/1538-7445.AM2017-2706

Oesophageal cancer: Commonly familial, possibly heritable.

23 Background: Oesophageal cancer (OC) accounts for 400 deaths in Ireland per year. Prognosis remains poor, and improved prevention is needed. Familial clustering has been described however, The Nordic Twin Study of Cancer does not support a strong hereditability. We investigated familial OC over a decade in Ireland. Methods: The independent records of two national referral services were reviewed: an oesophageal surgery database and a hereditary cancer genetics database. Demographic Factors including family history of OC were recorded from the surgical database. Families containing a single OC diagnosis were identified in the genetics database. Age at diagnosis and additional cancer diagnoses in the family were recorded. Results: 1238 patients with OC were seen at St. James’s Hospital from 2005 to 2015. Demographic characteristics are shown in Table. 641 patients (51%) had a family history of malignancy. Seventy eight (6.3%) reported a family history of OC, 6 (7.6%) of whom had two or more first degree relatives with OC and 10 (13%) had both a first degree and second degree relative with OC. More male relatives were diagnosed with OC than female (59% vs 41%).The majority (24%) with a family history were diagnosed at Stage III, the majority (29%) without a family history were diagnosed at Stage II. 1840 pedigrees from the genetic database were reviewed. No pedigree contained a Proband with OC.4.5%(n = 84) included at least one family member with OC. The median age at diagnosis was 64. Breast, colorectal and gastric were the most commonly associated cancers with median ages of 50,59 and 64 respectively. Conclusions: More than half of patients presenting with OC report a family history of cancer, with likely hereditary and environmental components. OC patients are rarely referred for genetic assessment, possibly due to treatment related morbidity and poor clinical outcome. [Table: see text]

Abstract 2549: Familial risk of upper gastrointestinal cancers by tumor location

Abstract Background: Upper gastrointestinal (UGI) cancers are within the most common malignancies worldwide. Familial clustering of UGI cancers and the significance of family history have been addressed in the past. We aimed to further elucidate the familial risk based on specified tumor locations. Methods: Using the Swedish Family-Cancer Database, we determined the familial risk of UGI cancer patients diagnosed between 1958 and 2012. Standardized incidence ratio (SIR) was used for calculating concordant and discordant familial cancers risks, stratified by tumor locations. All results were adjusted for sex, age group, period, and socioeconomic status. Results: Risk of esophageal cancer in first-degree relatives (FDRs) of esophageal cancer patients was 2•4-fold higher than that in those without such a family history. Familial risk for concordant cancer in upper and middle third of esophagus was 3•2- and 5•6-fold, respectively. Family history of esophageal cancer in lower part was associated with increased risk of gastric cardia cancer in FDRs and vice versa. Family history of both adenocarcinoma and SCC of esophageal cancer increased the familial risk of concordant (similar) and discordant subtypes. Occurrence of gastric cancer in the body and the antrum of stomach in a FDR were associated with an increased risk of gastric cancer 6- to 7-fold in the same location in family members, respectively. Conclusion: Family history of UGI cancers in some specific locations like upper and middle third of esophagus, body and antrum of stomach can be considered as an important predictive evidence for the same cancers in relatives. Citation Format: Elham Kharazmi, Masoud Babaei, Mahdi Fallah, Thianhui Chen, Kristina Sundquist, Kari Hemminki. Familial risk of upper gastrointestinal cancers by tumor location. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2549.

Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma.

A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk.