Incidence of esophageal and gastric cancers among Hispanics,non-Hispanic whites and non-Hispanic blacks in the United States: subsite and histology differences

Objective We examined subsite- and histology-specific esophageal and gastric cancer incidence patterns among Hispanics/Latinos and compared them with non-Hispanic whites and non-Hispanic blacks. Methods Data on newly diagnosed esophageal and gastric cancers for 1998–2002 were obtained from 37 population-based central cancer registries, representing 66% of the Hispanic population in the United States. Age-adjusted incidence rates (2000 US) were computed by race/ethnicity, sex, anatomic subsite, and histology. The differences in incidence rates between Hispanics and non-Hispanics were examined using the two-tailed z-statistic. Results Squamous cell carcinoma accounted for 50% and 57% of esophageal cancers among Hispanic men and women, respectively, while adenocarcinoma accounted for 43% among Hispanic men and 35% among Hispanic women. The incidence rate of squamous cell carcinoma was 48% higher among Hispanic men (2.94 per 100,000) than non-Hispanic white men (1.99 per 100,000) but about 70% lower among Hispanics than non-Hispanic blacks, for both men and women. In contrast, the incidence rates of esophageal adenocarcinoma were lower among Hispanics than non-Hispanic whites (58% lower for men and 33% for women) but higher than non-Hispanic blacks (70% higher for men and 64% for women). Cardia adenocarcinoma accounted for 10–15% of gastric cancers among Hispanics, and the incidence rate among Hispanic men (2.42 per 100,000) was 33% lower than the rate of non-Hispanic white men (3.62 per 100,000) but 37% higher than that of non-Hispanic black men. The rate among Hispanic women (0.86 per 100,000), however, was 20% higher than that of non-Hispanic white women (0.72 per 100,000) and 51% higher than for non-Hispanic black women. Gastric non-cardia cancer accounted for approximately 50% of gastric cancers among Hispanics (8.32 per 100,000 for men and 4.90 per 100,000 for women), and the rates were almost two times higher than for non-Hispanic whites (2.95 per 100,000 for men and 1.72 per 100,000 for women) but about the same as the non-Hispanic blacks. Conclusion Subsite- and histology-specific incidence rates of esophageal and gastric cancers among Hispanics/Latinos differ from non-Hispanics. The incidence rates of gastric non-cardia cancer are almost two times higher among Hispanics than non-Hispanic whites, both men and women. The rates of gastric cardia cancer are lower among Hispanics than non-Hispanic whites for men but higher for women. The rates of esophageal and gastric cardia adenocarcinomas are higher among Hispanics than non-Hispanic blacks.     

Prostate cancer: trends in mortality and stage-specific incidence rates by racial/ethnic group in Los Angeles County,California (United States)

Between 1976 and 1988 in the United States, the secular trends in age-adjusted incidence rates of prostate cancer were significantly different by racial/ethnic group (P<0.001), and increased significantly only among non-Hispanic Whites at a rate of 2.7 percent (95 percent confidence interval [CI]=2.3–3.1%) annually. While incidence rates of regional disease increased significantly (7.7 percent to 11.3 percent annually) among all racial/ethnic groups during this period, localized disease increased significantly only among non-Hispanic Whites, by 1.8 percent (CI=1.4–2.3%) annually. Prostate cancer mortality in Los Angeles County (California) remained constant among Hispanics, non-Hispanic Whites, and Asians, but increased 1.6 percent (CI=0–3.2%) annually among Blacks. While the increase in localized disease rates of non-Hispanic Whites may be due to increased detection of asymptomatic disease, this apparently has not occurred among other racial/ethnic groups in Los Angeles County. The secular increase in regional disease rates among all racial/ethnic groups without a concurrent increase in mortality (except Blacks), suggests increased accuracy of staging rather than a true increase in incidence may account for these trends. Adjusted for socioeconomic status, year and age at diagnosis, Black and Hispanic men were at significantly higher risk of being diagnosed with non-localized disease (odds ratio = 1.39 and 1.24, respectively) than were non-Hispanic Whites.Drs Ross and Bernstein are also with the Cancer Surveillance ProgramThis work was supported in part by grant CA17054 from the US National Institutes of Health, and grant SIG#20 from the American Cancer Society. Cancer incidence data were collected under Subcontract 050H-8709 with the California Public Health Foundation. The subcontract is supported by the California Department of Health Services as part of its statewide cancer reporting program, mandated by Health and Safety Code Section 210 and 2113.     

Incidence,Survival and Prevalence of Esophageal and Gastric Cancer in Linzhou City from 2003 to 2009

This study describes recent trends in incidence, survival and prevalence of subgroups of esophageal and gastriccancer in Linzhou city between 2003 and 2009. Data of esophageal and gastric cancer for the period of interestwere extracted from the Linzhou Cancer Registry. Using information on tumor morphology or anatomical site,data were divided into six groups; esophageal squamous cell carcinoma, esophageal adenocarcinoma, otherand unspecified types of esophageal cancer, and cardia, non-cardia, and unspecified anatomical site of stomachcancer. Incidence, survival and prevalence rates for each of the six cancer groups were calculated. The majorityof esophageal cancers were squamous cell carcinomas (82%). Cardiac cancer was the major gastric cancer group(64%). The incidence of esophageal squamous cell carcinoma and gastric cardiac cancer increased between 2003and 2009. Both esophageal and gastric cancer had a higher incidence in males compared with females. Overallsurvival was poor in all sub-groups with 1 year survival ranging from 45.9 to 65.6% and 5 year survival rangingfrom 14.7 to 30.5%. Prevalence of esophageal squamous cell carcinoma and gastric cardiac cancer was high(accounting for 80% overall). An increased focus on prevention and early diagnosis, especially in esophagealsquamous cell carcinoma and gastric cardiac cancer, is required.     

Incidence of cancer of the esophagus in the US by histologic type

Data from nine US population-based cancer registries participating in the Surveillance, Epidemiology, and End Results (SEER) program from 1973 through 1982 were analyzed to examine demographic characteristics related to the occurrence of the two major types of cancer of the esophagus. The overall annual incidence rate per 100,000 persons was 2.6 for squamous cell carcinoma and 0.4 for adenocarcinoma. The sex ratio for adenocarcinoma varied from one age group to the next and was highest in the 50- to 59-year-old group. It was relatively the same for squamous cell carcinoma. The male-to-female ratio was higher for adenocarcinoma (seven in whites and 10 in blacks) than for squamous cell carcinoma (three and four, respectively). The highest sex-specific ratio for adenocarcinoma occurred in the lower third of the esophagus. Blacks had a fourfold to fivefold higher rate of squamous cell carcinoma than whites, but the rate of adenocarcinoma in blacks was 30% of the rate in whites. The incidence of squamous cell carcinoma in black men and women increased by approximately 30% between 1973 and 1982, and the rate of adenocarcinoma among white men increased 74%. Nearly half of the squamous cell carcinomas occurred in the middle of the esophagus, whereas the majority (79%) of the adenocarcinomas arose in the lower third. These data suggest that the two major histologic types of esophageal cancer may be of different etiologic origin.     

Changing patterns of lung cancer incidence by histological type.

Using data from five registries covering 7% of the U.S. population, we investigated lung carcinoma incidence trends from 1969-86 by histological type, sex, race, age, calendar time period, and cohort year of birth. Among white men, squamous cell carcinoma was the most frequent histological type, but by the mid-1980s the age-adjusted rates were decreasing while rates of adenocarcinoma and small (oat) cell carcinoma continued to rise. Among white women, adenocarcinoma was the most frequent type, followed by small cell carcinoma, with rates of all histological types rising over the entire study period. Similar time trends were seen among blacks. Rates for squamous cell carcinoma among both sexes and adenocarcinoma among men, however, were considerably higher for blacks than whites, whereas no racial disparity was seen for small cell carcinomas. Rates for each histological type were higher among men than women, although male-female sex ratios diminished over time. Age-specific rates varied considerably by cohort year of birth; incidence of squamous cell carcinoma among men increased steadily among those born from the late 1800s to the first quarter of this century before declining among those born thereafter. Cohort peaks were also reached, although about 10 to 20 years later, for small cell carcinoma and adenocarcinoma, suggesting an eventual reduction in incidence in these histological types as well. For each type, the peak incidence occurred earlier for men than women. These differing incidence patterns add to the evidence that the mechanisms of lung carcinogenesis may vary by histological type.     

Sex differences in the prognosis after surgery for esophageal squamous cell carcinoma and adenocarcinoma

Some investigations suggest a better prognosis in women compared to men with esophageal cancer but these differences are uncertain. The aim of our study was to clarify whether sex influences the prognosis after esophagectomy for esophageal squamous cell carcinoma and esophageal adenocarcinoma. A population-based and nationwide cohort study included almost all patients who underwent esophagectomy for esophageal cancer in Sweden in 1987–2010, with follow-up until 2016. Patients’ sex was analyzed in relation to risk of mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for calendar period, age, education, comorbidity, tumor stage, neoadjuvant therapy, and surgeon volume. Among 1,816 participants, 1,024 (56%) had esophageal squamous cell carcinoma (355 [35%] women), and 792 (44%) had esophageal adenocarcinoma (103 [13%] women). Compared to men, women had a decreased overall all-cause mortality in esophageal squamous cell carcinoma (HR = 0.73, 95% CI 0.63–0.85). Stratified analyses showed decreased mortality limited to women aged >55 years (HR = 0.71, 95% CI 0.61–0.83), but in all tumor stages, particularly stages 0-I (HR = 0.54, 95% CI 0.37–0.79). Women also had decreased 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality in esophageal squamous cell carcinoma compared to men. For esophageal adenocarcinoma, no sex differences were found for any of the mortality outcomes. Thus, women who undergo esophagectomy for esophageal squamous cell carcinoma seem to have better prognosis than men, especially those with early tumor stages, whereas no sex differences in prognosis were found for esophageal adenocarcinoma.     

食管癌围手术期治疗的研究现状和进展

食管癌是我国常见的恶性肿瘤之一。西方国家以腺癌为主,亚洲地区则以鳞癌为主,我国食管癌中鳞癌患者约占95％。手术为食管癌的主要治疗方法,但单纯手术的效果并不尽如人意,5年生存率不足30％。为了提高手术效果,国内外很多研究探索了手术联合围手术期治疗的综合治疗模式。目前认为,在确保疗前准确分期的基础上,对于Ⅰ期及ⅡA期的患者可直接行手术治疗;对于ⅡB期及Ⅲ期的患者可行新辅助化疗或同步放化疗后进行手术。关于术后辅助治疗,目前尚缺乏有力的循证医学证据支持,但一些研究已初步证实术后辅助治疗的有效性。此外,围手术期分子靶向药物的应用及新辅助治疗疗效预测因子的研究也越来越成为研究的热点。     

Histologic Lung Cancer Incidence Rates and Trends Vary by Race/Ethnicity and Residential County

Introduction

Lung cancer incidence is higher among non-Hispanic (NH) blacks than among the NH white and Hispanic populations in the United States. However, national cancer estimates may not always reflect the cancer burden in terms of disparities and incidence in small geographic areas, especially urban-rural disparities. Moreover, there is a gap in the literature regarding rural-urban disparities in terms of cancer histologic type.

Targeted therapies for esophageal cancer

Esophageal cancer is a highly aggressive neoplasm. In 2005, 14,520 Americans will be diagnosed with esophageal cancer, and more than 90% will die of their disease. On a global basis, cancer of the esophagus is the sixth leading cause of cancer death worldwide. In fact, gastric and esophageal cancers together accounted for nearly 1.3 million new cases and 980,000 deaths worldwide in 2000-more than lung, breast, or colorectal cancer. Although esophageal squamous cell carcinoma cases have steadily declined, the incidence of gastroesophageal junction adenocarcinoma has increased 4%-10% per year among U.S. men since 1976, more rapidly than for any other cancer type, and parallels rises in population trends in obesity and reflux disease.With advances in surgical techniques and treatment, the prognosis of esophageal cancer has slowly improved over the past three decades. However, the 5-year overall survival rate (14%) remains poor, even in comparison with the dismal survival rates (4%) from the 1970s. The underlying reasons for this disappointingly low survival rate are multifold: (a) ineffective screening tools and guidelines; (b) cancer detection at an advanced stage, with over 50% of patients with unresectable disease or distant metastasis at presentation; (c) high risk for recurrent disease after esophagectomy or definitive chemoradiotherapy; (d) unreliable noninvasive tools to measure complete response to chemoradiotherapy; and (e) limited survival achieved with palliative chemotherapy alone for patients with metastatic or unresectable disease. Clearly, additional strategies are needed to detect esophageal cancer earlier and to improve our systemic treatment options. Over the past decade, the field of drug development has been transformed with the identification of and ability to direct treatment at specific molecular targets. This review focuses on novel targeted treatments in development for esophageal squamous cell carcinoma and distal esophageal and gastroesophageal junction adenocarcinoma.     

Secular trends in cancer mortality, California 1970-1998

BACKGROUND: Monitoring mortality is a meaningful way to evaluate the effectiveness of cancer control activities. Results of trend analysis for cancer related deaths by race/ethnicity in California from 1970 to 1998 are reported here. METHODS: Age-adjusted cancer mortality rates in California were used in the analysis of secular trends. Mortality patterns for selected cancers in all races combined are compared with similar patterns in the US for 1973-1998. RESULTS: The overall cancer mortality rates in California began to decline in 1987 in both men and women. Although mortality trends by site, sex, and race/ethnicity showed significant variations, the overall pattern in California is heavily influenced by trends for the non-Hispanic white (NHW) population and is very similar to the patterns in the US with minor differences in the magnitude and trend. CONCLUSIONS: This is the first time that secular trends in cancer mortality for California are presented by race and ethnicity. Despite notable racial differences, the overall trend follows a declining pattern. Detailed explanation of the reasons behind the observed patterns is not included in this report. Some of the differences between California and the US, however, can be explained by differences in the racial and ethnic composition of the two populations. Approximately 45% of the California population has Hispanic (HSP) or Asian origins among whom cancer mortality rates are substantially lower. Another factor is the difference in the intensity and coverage of cancer related activities such as tobacco control. Prevalence of smoking in California is much lower than the rest of the US.     

Racial treatment trends in localized/regional prostate carcinoma: 1992-1999

BACKGROUND: African-American men have a greater incidence of and mortality from prostate carcinoma compared with white men, and they are less likely to receive definitive therapy (radical prostatectomy or external beam radiation therapy). During the 1990s, the use of brachytherapy increased; however, its influence on racial and ethnic prostate carcinoma treatment trends remains unclear. The objective of this study was to describe treatment trends over the period 1992-1999 for localized/regional prostate carcinoma among white, Hispanic, and African-American men. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry data from 1992 through 1999, logistic regression models were used to determine whether the odds of receiving a specific treatment modality differed by racial and ethnic group and whether the differences changed over time when the models were adjusted for age, marital status, tumor grade, and SEER site (geography). RESULTS: The authors identified 142,340 men, including white men (81.6%), Hispanic men (6.4%), and African-American men (12.0%). Racial and ethnic differences in the rates of use of androgen-deprivation therapy/expectant management were noted; however, these differences appeared to lessen over time (P < 0.001). The rate of utilization of radical prostatectomy increased for Hispanic men, remained flat for African-American men, and decreased for white men. The utilization of brachytherapy and combination therapy increased for all three groups; however, the greatest increase in utilization was among white men. CONCLUSIONS: Further research will be required to determine the patient-level and provider-level variables that influence racial and ethnic treatment differences in localized/regional prostate cancer.     

Epidemiology of upper gastrointestinal malignancies

The demographics of esophageal and gastric cancer have been changing dramatically in the United States over the past several decades. While incidence rates for esophageal squamous cell carcinoma and distal gastric carcinoma have been declining, the trends for adenocarcinoma of the esophagus and proximal stomach have been rising rapidly, particularly among white males. The incidence of these upper gastrointestinal (GI) malignancies varies widely based on geographic location, race, and socioeconomic status. The primary causes of squamous cell carcinoma of the esophagus are tobacco use and alcohol consumption, whereas the main risk factors for adenocarcinoma of the esophagus are gastroesophageal reflux disease and obesity. Dietary factors and Helicobacter pylori infection play an important role in the development of gastric cancer. Understanding the epidemiology and etiologies of esophageal and gastric carcinomas will lead to the development of interventions for screening and prevention in high-risk populations.     

食管癌发病水平及变化趋势

食管癌在世界癌症发病中占第8 位,位居全球癌症死因的第6 位。食管癌预后较差,对人类健康的危害严重。我国是食管癌高发国家,也是世界上食管癌新发病例最多的国家。食管癌的组织学类型主要分为食管鳞癌和食管腺癌,从上世纪70代开始许多西方国家的食管鳞癌发病率呈下降趋势,与此相反食管腺癌的发病率迅速增加,成为增长速度最快的恶性肿瘤之一。中国人群食管癌的病理类型以鳞状上皮细胞癌为主,该组织学类型占我国食管癌发病的90% 以上。我国食管癌发病率呈明显的地区差异,食管鳞癌和食管腺癌的发病水平、地理分布、时间变化趋势及发病危险因素存在较大差别。本文阐述食管癌发病水平及变化趋势,以期为我国食道癌预防和控制策略制定、实施与效果评估提供基础信息。      

Late Stage and Grave Prognosis of Esophageal Cancer in Thailand

Background: Esophageal cancer is one of the major health concerns in Southeast Asian countries, includingThailand. However, only a limited number of studies have been reported from this region. This study wasdesigned to evaluate the prevalence, clinical characteristics and survival rate of esophageal cancer in Thailand.Materials and Methods: Clinical information, histological features and endoscopic findings were collected froma tertiary care center in central region of Thailand between September 2011- November 2014 and reviewed.Results: A total of 64 esophageal cancer patients including 58 men and 6 women with mean age of 62.6 yearswere enrolled. Common presenting symptoms were dysphagia (74%), dyspepsia (10%) and hematemesis (8%).Mean duration of symptoms prior to diagnosis was 72 days. Esophageal stenosis with contact bleeding was themost common endoscopic finding (55.6%). The location of cancer was found in proximal (16%), middle (50%)and distal (34%) esophagus. Squamous cell carcinoma was far more common histology than adenocarcinoma(84.2% vs 10.5%). However, esophageal adenocarcinoma was significantly more common than squamous cellcarcinoma in distal area of esophagus (100% vs 22.9%; p=0.0001, OR=1.6, 95%CI=1.1-2.2). Esophageal cancerstages 3 and 4 accounted for 35.2% and 59.3% respectively. Overall 2-year survival rate was 20% and only 16%in metastatic patients. Conclusions: Most esophageal cancer patients in Thailand have squamous cell carcinomaand nearly all present at advanced stage with a grave prognosis. Screening of high risk individuals and earlydetection might be important keys to improve the survival rate and treatment outcome in Thailand.     

Mistaken identity of widely used esophageal adenocarcinoma cell line TE-7

Cancer of the esophagus is the seventh leading cause of cancer death worldwide. Esophageal carcinoma cell lines are useful models to study the biological and genetic alterations in these tumors. An important prerequisite of cell line research is the authenticity of the used cell lines because the mistaken identity of a cell line may lead to invalid conclusions. Estimates indicate that up to 36% of the cell lines are of a different origin or species than supposed. The TE series, established in late 1970s and early 1980s by Nishihira et al. in Japan, is one of the first esophageal cancer cell line series that was used throughout the world. Fourteen TE cell lines were derived from human esophageal squamous cell carcinomas and one, TE-7, was derived from a primary esophageal adenocarcinoma. In numerous studies, this TE-7 cell line was used as a model for esophageal adenocarcinoma because it is one of the few esophageal adenocarcinoma cell lines existing. We investigated the authenticity of the esophageal adenocarcinoma cell line TE-7 by xenografting, short tandem repeat profiling, mutation analyses, and array-comparative genomic hybridization and showed that cell line TE-7 shared the same genotype as the esophageal squamous cell carcinoma cell lines TE-2, TE-3, TE-12, and TE-13. In addition, for more than a decade, independent TE-7 cultures from Japan, United States, United Kingdom, France, and the Netherlands had the same genotype. Examination of the TE-7 cell line xenograft revealed the histology of a squamous cell carcinoma. We conclude that the TE-7 cell line, used in several laboratories throughout the world, is not an adenocarcinoma, but a squamous cell carcinoma cell line. Furthermore, the cell lines TE-2, TE-3, TE-7, TE-12, and TE-13 should be regarded as one single squamous cell carcinoma cell line.     

Patterns and trends in esophageal cancer mortality and incidence in Europe (1980–2011) and predictions to 2015

BackgroundOver the last few decades, esophageal cancer incidence and mortality trends varied substantially across Europe, with important differences between sexes and the two main histological subtypes, squamous cell carcinoma (ESCC) and adenocarcinoma (EAC).Patients and methodsTo monitor recent esophageal cancer mortality trends and to compute short-term predictions in the European Union (EU) and selected European countries, we analyzed data provided by the World Health Organization (WHO) for 1980–2011. We also analyzed incidence trends and relative weights of ESCC and EAC across Europe using data from Cancer Incidence in Five Continents.ResultsLong-term decreasing trends were observed for male esophageal cancer mortality in several southern and western European countries, whereas in central Europe mortality increased until the mid-1990s and started to stabilize or decline over the last years. In some eastern and northern countries, the rates were still increasing. Mortality among European women remained comparatively low and showed stable or decreasing trends in most countries. Between 2000–2004 and 2005–2009, esophageal cancer mortality declined by 7% (from 5.34 to 4.99/100 000) in EU men, and by 3% (from 1.12 to 1.09/100 000) in EU women. Predictions to 2015 show persistent declines in mortality rates for men in the EU overall, and stable rates for EU women, with rates for 2015 of 4.5/100 000 men (about 22 300 deaths) and 1.1/100 000 women (about 7400 deaths). In northern Europe, EAC is now the predominant histological type among men, while for European women ESCC is more common and corresponding rates are still increasing in several countries.Conclusion(s)The observed trends reflect the variations in alcohol drinking, tobacco smoking and overweight across European countries.     

Epidemiologic differences in esophageal cancer between Asian and Western populations

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.     

Carcinoma of the esophagus with mixed basaloid squamous and glandular differentiation

Esophageal cancer is the third most common gastrointestinal cancer and ranks among the ten commonest cancers worldwide. Histologically, approx 60% of esophageal cancers are adenocarcinomas and 40% are squamous cell carcinomas (SCC). Other rare cancers of the esophagus include small-cell carcinomas, squamous cell carcinomas with sarcomatous features, adenoid cystic carcinomas, and mucoepidermoid carcinomas. Basaloid squamous cell carcinoma (BSCC) or basaloid squamous carcinoma (BSC) is a distinct clinicopathological entity, seen more frequently in elderly males. Stage at presentation is often advanced and regional adenopathy or distant metastases are not uncommon at presentation. We describe an unusual case report of esophageal BSCC with glandular differentiation. The clinical significance of glandular differentiation in this rare type of tumor is not known.     

EPHX1 polymorphisms do not modify esophageal carcinoma susceptibility in Dutch Caucasians

Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Crucial risk factors are exposure to toxins or carcinogens. Microsomal epoxide hydrolase (mEH) is a biotransformation enzyme essential for the detoxification of xenobiotics. Polymorphisms in exon 3 and exon 4 of the microsomal epoxide hydrolase gene (EPHX1) modify catalytic activity of this enzyme and subsequently may play a role in EC etiology. This case-control study investigated whether these polymorphisms in the EPHX1 gene influence esophageal cancer susceptibility in a Dutch Caucasian population. A case-control study including 349 Caucasian EC patients and 581 Caucasian healthy controls was conducted and the polymorphisms Tyr113His (exon 3) and His139Arg (exon 4) in the EPHX1 gene were determined, using polymerase chain reaction. The distribution of exon 3 and exon 4 genotypes were compared between cases and controls. Analyses included a stratification according to tumor histology; esophageal adenocarcinoma (EAC) or squamous cell carcinoma (ESCC). Furthermore, on the basis of allelic in vitro enzyme activity assays, exon 3 and 4 genotypes were combined and categorized according to their predicted high, medium or low enzyme activity. Homozygosity and heterozygosity for both exon 3 and 4 polymorphisms were correlated with a decreased esophageal squamous cell carcinoma risk. Heterozygosity and homozygosity for both polymorphisms correlated with an increased and a decreased esophageal adenocarcinoma risk, respectively. Predicted intermediate and high activity genotypes were risk and protective factors for esophageal squamous cell carcinoma and esophageal adenocarcinoma, respectively. However, none of these associations were statistically significant. In conclusion, the polymorphisms in exon 3 and exon 4 of the EPHX1 gene do not seem to be modifiers of esophageal squamous cell carcinoma or esophageal adenocarcinoma risk in Dutch Caucasians.