| BackgroundEsophageal cancer is one of the most common cancers, with 462,000 new cases and 386,000 deaths in 2002 worldwide. More than 80% of esophageal cancers occur in the developing countries. From recent studies, smoking and alcohol drinking were found to be the major risk factors for ESCC in low risk countries, however, they were not determinant risk factors for ESCC in high risk countries. Low vegetable and fruit intake, low socioeconomic status and family history of ESCC are major risk factors for ESCC in high risk populations. Tooth loss/poor oral hygiene, polycyclic aromatic hydrocarbons (PAHs) and exposure to mycotoxin are considered to be possible risk factors for ESCC. However, none of these risk factors has shown a strong association with ESCC. Today, there is growing concerns about infectious agents as risk factors for cancer. In 2008, Dr zur Hausen was awarded the Nobel Prize for his discovery of human papilloma virus causing cervical cancer. In 2002 about 17.8% of cancers (1.9 million cases) were attributable to infectious agents (Hepatitis B and C viruses, Helicobacter pylori, etc.) worldwide. The disease burden of infection-related cancers in low-and medium-income nations is much heavier than that in high-income nations.In 1982, HPV was suggested as a risk factor for esophageal cancer by Syrjanen. And in the following two decades, HPV infection rate in esophageal cancer varied in different studies. Few studies have been conducted to explore the association between HPV and esophageal cancer in China and different results were shown when diverse samples including tissue, cytology and serum were used. Although relationship of HPV with several cancers (cervical cancer., tonsillar cancer)has been established, yet carcinogenesis of HPV in the esophagus remains unknown. Association between HPV and esophageal cancer stays controversial.We have previously conducted two studies of HPV and ESCC in Linxian, China. One was a prospective study that evaluated the association between seropositivity for HPV antibodies and the risk of having ESCC. The other was a study that detected the prevalence of HPV in.esophageal cytology specimens using Hybrid Capture 2 test. These two studies found no association between HPV and ESCC. To further study HPV in ESCC, we need to detect HPV from ESCC tissues and to evaluate the carcinogenicity of HPV in HPV positive cases.Epidemiology studies have demonstrated that smoking, alcohol drinking, low vegetable intake and low fruit intake are risk factors of esophageal cancer. Most previous studies of attributable fraction of cancers were conducted in high income countries, while few studies were carried out in low income countries. Therefore, the second part of the thesis is to estimate the proportion of esophageal cancer mortality and incidence attributable to known risk factors in China.ObjectiveTo definitively evaluate the association between HPV and ESCC by determining the prevalence of HPV in ESCC tumors, the activity of HPV in HPV positive cases and comparing HPV prevalence results from different laboratories.To estimate the proportion of esophageal cancer deaths and cases attributable to smoking, alcohol drinking,low vegetable or fruit intake and provide evidence for decision makers on esophageal cancer control in China.Materials and Methods272 consecutive incident histopathologically confirmed ESCC cases who "were≥18 years of age and undergoing surgical resection at Yaocun Commune Hospital in Linxian, China were collected from October 2006 to March 2007. All subjects provided written informed consent. Sample collection and process were based on,a standardized protocol designed to minimize the possibility of tissue contamination by environmental HPV. Tumor tissues were classified as frozen tissues and paraffin-embedded formalin fixed tissues. Frozen tissues were tested for HPV DNA using PGMY primers and HPV16/18 E6/E7 primers at Johns Hopkins University. Paraffin-embedded formalin fixed tissues were detected for HPV DNA at CICAMS using PCR with SPF10 primers (DDL Diagnostic Laboratories, Netherlands). HPV DNA positive cases were evaluated for HPV carcinogenicity using immunohistochemical analysis of p16INK4a overexpression and enzyme-linked immunosorbent assays with glutathione S-transferase fusion proteins testing for anti-E6 and anti-E7 antibodies (available for HPV types 16 and 18).We calculated the proportion of esophageal cancers attributable to tobacco smoking, alcohol drinking, low vegetable and fruit consumption. Exposed data on smoking, alcohol drinking, low vegetable and fruit intake were from large scale national surveys of representative samples from Chinese population. Data on relative risk between smoking, alcohol drinking, low vegetable and fruit intake and esophageal cancer were derived from the Meta-analyses and large scale prospective studies. Esophageal cancer mortality and incidence were originated from the third national death cause survey and cancer registries in China.Results1. Association between HPV and ESCC Patients in our study came from 13 of the 31 Provinces, Municipalities, and Autonomous Regions of China, including both the high risk Taihang mountain region (27.6%) and other areas (72.4%). Median age of 272 esophageal cancer cases was 60 years (age range:38-79 years). More than two thirds of the cases were men and nearly all were married (98%). One hundred and sixty (58.8%) of the patients were ever smokers. All but 2 of them were males. Prevalence of current alcohol drinking was low (9.9%). Similarly,110 (40.4%) of the patients were ever drinkers, all of them were male. Among 272 esophageal cancer cases,102 (37.5%) were never smokers and never, drinkers,83 of whom were female. Sixty seven patients (24.6%) had a family history of cancer, among them,55 (20.2%) had esophageal cancer family history. Among the 272 cases,3 were positive for HPV. One male case was tested weakly positive for HPV89 using PGMY consecutive primers and Roche HPV Linear Array Assay. Two cases were tested weakly positive using SPF10 primers and LiPA genotyping tests:one female for HPV 16 and one male for HPV31. Tests for HPV carcinogenicity showed that none of the 3 HPV positive cases exhibited p16INK4a protein overexpression and the HPV 16 positive case was seronegative for HPV 16 E6/E7 antibodies.2. Attributable causes of esophageal cancer in China We estimated that a total of 85,421 esophageal cancer deaths and 106,167 cases were attributable to 4 known risk factors in China in 2005, including smoking, alcohol drinking, low vegetable intake and low fruit intake. Among them,24,626 esophageal cancer deaths and 30,560 incident cases were attributable to smoking (23,528 deaths and 29,187 cases in men (17.9%) and 1,098 deaths and 1,373 cases in women (1.9%)). A total of 20,749 deaths and 25,748 cases were attributable to alcohol drinking (19,989 deaths and 24,797 cases in men (15.2%) and 760 deaths and 951 cases in women (1.3%)). Increasing consumption of vegetables to the highest quintile could avoid 8,005 esophageal cancer deaths and 9,956 cases, including 5,628 deaths and 6,982 cases among men (4.3%) and 2,377 deaths and 2,974 cases among women (4.1%). Increasing consumption of fruit to the highest quintile could avoid 52,058 esophageal cancer deaths and 64,745 cases, including 35,666 deaths and 44,244 cases among men (27.1%) and 16,392 deaths and 20,501 cases among women (28.0%).Conclusions1. The result of our study is similar to the two previous studies of HPV and ESCC in Linxian. HPV is not a risk factor of esophageal cancer in Chinese population. HPV is not involved in esophageal carcinogenesis.2. In Chinese population, about half of esophageal cancer deaths or cases are attributable to smoking, alcohol drinking, low vegetable intake and low fruit intake. Smoking and alcohol drinking are responsible for about 30% of esophageal cancer mortality or incidence.3. We need to conduct large scale, multicenter studies to demonstrate other important risk factors of esophageal cancer.
|
PDF Full Text Request