Spatio-temporal Trends And Reproductive Factors For Esophageal Cancer In Taixing, Jiangsu

Background and ObjectivesEsophageal cancer (EC) has poor prognosis as well as low 5-year survival rate as one of the least learned and deadliest cancers. In 2012 results from the IARC, we observed that EC is ranked as the 8th most common of cancer including 45.6 thousand new cases and the 6th most common cause of cancer deaths which includes nearly 40 thousand new deaths per year worldwide, with China making up nearly 50% of total cases and deaths. Based on the 2010 cancer registration in China, new cases of EC were 287,632 and deaths were 208,473 respectively.More than 20 histological subtypes of EC were divided by WHO guideline but squamous cell carcinoma (ESCC) combined with adenocarcinoma (EAC) together occupies approximately 90% of all the detected lesions of EC. EC represents a biologically and genetically heterogeneous cluster of cancers with multi-factorial etiologies both environmental and genetic. The incidence rates change globally and locally by approximately 20-fold among the highest area vs. the lowest area. The obvious geographic difference in different population potentially suggests that environmental or lifestyle factors may become the main reasons during the development and progression of EC. Some factors that could induce chronic irritation and inflammation for esophageal mucosa may expand the morbidity of ESCC. On the other hand, some risk factors are thought to add the risk of incidence rate for EAC such as gastroesophageal reflux disease (GRED) and cigarette smoking and obesity. Genetic or other endogenous elements are also key contributors probably to affect susceptibility to the development of EC as showed by familial clusters and candidate gene association of EC, which have been reported in several countries despite the results have been inconsistent.EC morbidity rate is 2.4 times more common among men than women worldwide. Males, in general, have a higher morbidity rate of EC than rates among females. However, it cannot be explained these distinctions between the gender difference only due to the prevalence of known risk factors for EC. The noticed phenomenon for EC suggests that there should be a gender-related mechanism involved in the pathogenesis of this kind of cancer. It recently has been postulated that hormonal factors might play a key effect on the etiology of EC.A population-based case-control study on the etiology of EC was conducted from October 2010 to now in Taixing city of China. This thesis was divided into two parts equally by using a series of the study’s data and materials. In part Ⅰ:we used cancer registration data to investigate if there was non-random spatial distribution of EC to explore the relationships between EC and geographic factors. In part Ⅱ:we gathered needed data from this case-control study on EC and then conducted a meta-analysis to further evaluate the associations between EC’s risk and female reproductive factors. My goal is not to offer solutions, but simply to provide information. I hope that the findings may help guide local government health departments to monitor, assess and adjust cancer prevention and control strategies for the corresponding targeted population and hotspot regions, and provide evidence for researchers to further study preventive measures from a new angle.Subjects and Methods1. Data from Taixing cancer registry was utilized to measure the crude rates, age-specific rates, age-standardized rates and county-specific incidence rates. Atlases on the annual distribution of EC incidence rate in Taixing area were drawn for the purpose of showing spatial and temporal variations of EC epidemic. In addition, Scan statistics were measured to identify clusters of EC cases in either a purely spatial or a space-time fashion. PAR% was applied to explore statistically significant and/or population health related clusters.2. This study was implemented to gather enough data containing related study factors from both environmental and genetic fields for EC. We identified newly diagnosed women SCC cases of esophagus aged 44-85 years from October 2010 to March 2012. The study cases were recruited from patients who were undergoing endoscopy in the three largest hospitals of Taixing area. More than 90% of the patients in this city and the neighboring rural area are referred to these hospitals. Control group was randomly chosen from the Taixing populace registry list and matched to the corresponding cases for age (±5 years) and gender with a case/control ratio of about 1 to 1.5.3. Relevant studies were reviewed through the electronic database-PubMed in our meta-analysis. These study-specific relative risks (RR) with corresponding 95% confidence interval (CI) in all analyses were used, and multiple summary relative risk (SRR) estimates were measured. We conducted subgroup analyses and adopted meta-regression techniques to detect potential sources of heterogeneity. Sensitivity analysis was applied to identify whether pooled results would be influenced by individual recruiting studies and publication bias was evaluated by Begg’s funnel plots and the Egger regression asymmetry test.All data statistical analyses were performed by SAS 9.1 or STATA 11.0. All reported probabilities (p values)<0.05 were considered statistically significant except the heterogeneity for which p≤0.1 as the threshold for considered significance and total statistical tests were set two-sided.Results1. Spatio-temporal trends and hotspot detection of esophageal cancer in Taixing, China during 2004-2013There are 6568 new cases of EC among which 4396 are male and 2172 are female during 2004 and 2013. The incidence rate of EC cases was still obviously high although EC cases were reported in every year and declined obviously in year 2013. We estimated that the total crude rate of EC was 53.1 per 100,000 population/year. After using the population of the world standard, the age-standardized ratio was 34.3 per 100,000 population/year. The age groups from 55 to 74 year old contributed about 75% of all reported cases, while the 80 to 84 age group reached the highest incidence of this disease. The results from PAR%, RR and space-time cluster analysis indicated a similar space-time pattern in the distribution of EC, which was clustered in the middle parts of Taixing city.2. Reproductive factors and the incidence of esophageal cancer in women:a case-control study and meta-analysis2.1 Case-control studyIn total,181 ESCC cases and 223 controls were administered issues on reproductive history containing stages of pregnancy, parity and menopause. The age of cases is mainly between 60 and 79 year old which occupied more than 80% of all cases. The odds ratio for esophageal cancer was declined among large number of births compared with small number of births (≥6 versus 0-1) which is similar to the result of number of pregnancies. We also found slightly decreased odds ratio associated with late age at menopause compared with early age at menopause. No significant association was obviously explored in other study factors for EC risk.2.2 Meta-analysisThe results were generally consistent with the findings above and extended to EC not just ESCC. The summary relative risk (SRR) estimate was reduced for parity (SRR= 0.79,95% CI:0.70-0.89) and decreased among those undergoing a late menopause versus early menopause (SRR=0.72,95% CI:0.55-0.95). However, in our meta-analysis we also added other reproductive factors and found hormone replacement therapy (SRR=0.67,95% CI:0.56-0.81) had an association with an inverse effect of EC risk. Similar result was obtained for ever breastfeeding.ConclusionsIn Taixing city,1) crude incidence rates for EC decreased steadily during the interval of 2004 and 2013 with a similar trend among men and women each year.2) The analyses using GIS technique and temporal and spatial statistics could study the temporal and spatial distribution of EC in a given geographical area where EC is highly prevalent.3) Some reproductive factors appeared to be related to the incidence rate of ESCC among women in our study.4) Our meta-analysis further supported reproductive factors’substantial influence, which could be causally linked with EC.