Morbidity Trends And Familial Aggregation Of Esophageal Cancer In Taixing County

Background and ObjectivesChina is an area with one of the highest incidences of EC worldwide. Taixing county of Jiangsu Province located in one of the six high-risk areas in China, EC ranked as the1st leading cause of death in this area. From1999to2002, the incidence of uppergastrointestinal tract cancers decreased, but the time trend of EC in recent years has not been reported.The striking geographic variation suggests that environmental factors are major contributors to the etiology of EC. However, in addition to environmental factors, genetic and endogenous factors may also affect human susceptibility to EC. Since2010, we conducted a population-based case-control study on the etiology of EC in Taixing. During the survey, we found that the proportion of people who had a positive family history (FH) of cancer was quite high. Several studies conducted in other EC high-risk areas such as Henan and Shanxi demonstrated familial aggregation of EC. But the subjects of these studies were limited to esophageal squamous cell carcinoma (ESCC) or EC without histological classification of subtypes. Evidences showed that ESCC and esophagealadenocarcinoma(EAC) have different etiology. However, few studies have analyse ESCC and EAC seperately.In addition, according to different study designs, there are different methods for measure of FH in familial aggregation studies. In the case-control design, the cases and the controls are the outcomes, and the disease status in their relatives is the risk factor, a proxy for exposure. In the reconstructed cohort design, the disease status of precisely one relative-the case or control proband-defines FH, the reconstructed cohorts of case and control subjects are evaluated for the cumulative risk of disease. To date, exploration for the familial risk of EC are predominantly using the case-control design, data from the reconstructed cohorts are still scarce.Thus, in part1of this research, datafrom population-based cancerregistries in Taixingwas used to describe theepidemiological characteristics andtime trends in theincidence ofEC.In part2, weused part of the information collected from the population-based case-control study in Taixing to investigate familial aggregation in subtypes of EC using two different measures of FH. aiming to determine whether patients with EC have an increased likelihood of having a positive FH of cancer and whether the relatives of an affected individual have an increased risk of the disease.Subjects and Methods1. Data from population-based cancer registries in Taixingwas used to calculate the crude, age-specific, cumulative and age-adjusted incidencerates. and time trends in the incidence of EC.2.All subjects were restricted to local inhabitants who have lived in Taixing for at least5years prior to diagnosis for cases or interview date for controls. The study population was recruited from patients undergoing endoscopy at the four largest hospitals of Taixing. All cases were diagnosed histologically, and most of the histological slides were reviewed by the study pathologist. Control subjects were randomly selected from the Taixing population register and matched to resemble the age and sex distribution among the cases.With written informed consent, all subjects underwent face-to-face interviews by trained interviewers using a standardized questionnaire to obtain informationon demographic characteristics, lifestyles and FH of cancer.An unconditional logistic regression model was used to estimate the risk of ESCC and EAC associated with a FH of cancers. Model parameters were estimated by the maximum likelihood method. From these estimates, odds ratios (ORs) with their95%confidence intervals (CIs) were calculated. Based on the kin-cohort data, two cohorts were constructed, consisting of the first-degree relatives (FDRs) of cases and the FDRs of controls. Each FDRs of the cases and controls was considered to be a study subject. Study subjects were followed until the occurrence of EC, or death from another cause, or the date of the study interview. The exposed cohort was composed of the FDRs of the cases, and the unexposed cohort was made up of the relatives of the controls. Cumulative hazard curves were constructed, which describe the cumulative risk of being diagnosed with EC over time. The occurrence of EC among the relatives of cases and controls was compared for each familial relationship by using the Cox proportional hazards model.All data were analyzed by using SAS version9.1software (SAS Institute, Inc., Cary, North Carolina).Results1. Epidemiological characteristics and the trends in the incidence of EC in Taixing from2006to20101.1From2006to2010, the average crude incidence of EC was56.4per100000, the male to female ratio was1.96:1. The cumulative incidence of EC from0to74years old were6.2%and3.0%for men and women, respectively.1.2From2006to2010, according to the Chinese standard population, age-standardised incidence of EC decreased from39.8to34.3per100000, according to the world’s population, age-standardised incidence of EC decreased from25.9to20.4per100000. The age-standardised incidence (according to the Chinese population) of EC decreased from51.3to46.1per100000men, and from27.2to21.3per100000women.2. Familial aggregation analysis2.1Demographics A total of583ESCC,66EAC cases and774controls were included in this study. The participation rate of cases and controls was78and75.4%respectively.2.2Case-control design(1) ESCC:①Excess ESCC risk was associated with a FH of any cancer (OR =1.40,95%CI:1.12-1.76), FH of EC in FDRs was associated with a1.91-fold increase of ESCC risk. In general, the risk of ESCC increased monotonically with greater number of affected relatives. Among specific sites, FH of gastric cancer was associated with an increased risk of ESCC, however, a FH of liver cancer, colorectal cancer or pancreatic cancer was not associated with an increased risk of ESCC.②The ESCC odds ratios associated with parents and siblings histories of any malignant tumor were1.37and1.34, respectively. FH of EC inparents and siblings was associated with a1.63and2,27-fold increase of ESCC risk respectively.(2) The risk of EAC increased with greater numbers of affected relatives but there was no statistical significance. No association was seen between FH of cancer in parents or siblings and risk of EAC.2.3Interaction analysis There was no interactionsbetween the FHof esophageal EC and alcohol consumption on the occurrence of ESCC.2.4Kin-Cohort analysisThere were4411FDRs of the583cases and5780FDRs of the774controls. A total of236(5.35%) and173(2.99%)relatives of case and control subjects, respectively, werereported to have had a diagnosis of EC. The cumulative risk of getting EC in the FDRs of the cases was12.26%by the age of75, compared to7%for the relatives of controls (HR=1.93;95%CI,1.58-2.34).Conclusions1. The age-standardised incidence of oesophageal cancer decreased from2006to2010but still higher than many other districts.2. Having a FH of any malignant cancer, especially FH of EC in FDRs was associated with increasedrisk of ESCC, but no association was seen for EAC.3. The cumulative risk of getting EC in the FDRs of the ESCC cases was higher than that of the FDRs of controls.4. We demonstrated familial aggregation of ESCC, but not EAC.