Serum superoxide dismutase activity and risk of esophageal cancer in a nested case-control study.

Use of oral bisphosphonates has increased dramatically in the United States and elsewhere. Esophagitis is a known adverse effect of bisphosphonate use, and recent reports suggest a link between bisphosphonate use and esophageal cancer, but this has not been robustly investigated. To investigate the association between bisphosphonate use and esophageal cancer. Data were extracted from the UK General Practice Research Database to compare the incidence of esophageal and gastric cancer in a cohort of patients treated with oral bisphosphonates between January 1996 and December 2006 with incidence in a control cohort. Cancers were identified from relevant Read/Oxford Medical Information System codes in the patient's clinical files. Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals for risk of esophageal and gastric cancer in bisphosphonate users compared with nonusers, with adjustment for potential confounders. Hazard ratio for the risk of esophageal and gastric cancer in the bisphosphonate users compared with the bisphosphonate nonusers. Mean follow-up time was 4.5 and 4.4 years in the bisphosphonate and control cohorts, respectively. Excluding patients with less than 6 months' follow-up, there were 41 826 members in each cohort (81% women; mean age, 70.0 (SD, 11.4) years). One hundred sixteen esophageal or gastric cancers (79 esophageal) occurred in the bisphosphonate cohort and 115 (72 esophageal) in the control cohort. The incidence of esophageal and gastric cancer combined was 0.7 per 1000 person-years of risk in both the bisphosphonate and control cohorts; the incidence of esophageal cancer alone in the bisphosphonate and control cohorts was 0.48 and 0.44 per 1000 person-years of risk, respectively. There was no difference in risk of esophageal and gastric cancer combined between the cohorts for any bisphosphonate use (adjusted hazard ratio, 0.96 [95% confidence interval, 0.74-1.25]) or risk of esophageal cancer only (adjusted hazard ratio, 1.07 [95% confidence interval, 0.77-1.49]). There also was no difference in risk of esophageal or gastric cancer by duration of bisphosphonate intake. Among patients in the UK General Practice Research Database, the use of oral bisphosphonates was not significantly associated with incident esophageal or gastric cancer.

Angiotensin-Converting Enzyme Inhibitors and Risk of Esophageal and Gastric Cancer: A Nested Case-Control Study

Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer deaths or endoscopy rates, which could be higher in bisphosphonate users and lead to more cancers being diagnosed at a stage when their esophageal or gastric location could be accurately distinguished. We conducted a register-based, open cohort study using national healthcare data for Denmark. Upper endoscopy frequency, cancer incidence and mortality was examined in 30,606 alendronate users (female, age 50+) and 122,424 matched controls. Primary outcomes were esophageal cancer incidence and death because of esophageal cancer. The analysis showed that alendronate users were more likely to have undergone recent upper endoscopy (4.1 versus 1.7%, p < 0.001). Alendronate users had a lower risk of incident gastric cancer [odds ratio (OR) 0.61; 95% confidence interval (CI): 0.39-0.97) and no increased risk of esophageal cancer (OR 0.71; 95% CI: 0.43-1.19). Risk reductions were greater in users with 10+ prescriptions. The risk of dying of esophageal cancer was significantly reduced in alendronate users after 3 years OR 0.45 (95% CI: 0.22-0.92) but not after 9 years (OR 1.01; 95% CI: 0.52-1.95). An additional comparison with etidronate users revealed no statistically significant difference in outcomes. In conclusion, we found no excess in esophageal cancer deaths or incidence. The early decrease in esophageal cancer rates may relate to the greater use of endoscopy before starting alendronate. Longer term observations also indicated no excess risk of esophageal cancer death and a significantly decreased risk of gastric cancer death.

ABSTRACTSeveral case-control studies have associated dietary patterns with esophageal cancer (EC) risk, but prospective studies are scarce. We investigated dietary pattern and EC mortality risk associations by smoking status. Participants were 26,562 40- to 79-yr-old Japanese men, who enrolled in the Japan Collaborative Cohort Study between 1988 and 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for EC mortality in nonsmokers and smokers were estimated using Cox proportional models. During follow-up (1988–2009), 132 participants died of EC. Using a baseline food frequency questionnaire and factor analysis, vegetable, animal, and dairy product food patterns were identified. EC risk decreased significantly with a higher factor score for the dairy product pattern (Ptrend = 0.042) and was more pronounced in smokers [multivariable HR (4th vs. 1st quartiles) = 0.57, 95% CI: 0.30, 1.09; Ptrend = 0.021]. Neither vegetable nor animal food patterns were significant overall; however, EC risk increased with a higher factor score for the animal food pattern in nonsmokers [multivariable HR (4th vs. 1st quartiles) = 6.01, 95% CI: 1.17, 30.88; Ptrend = 0.021], although the small number of events was a limitation. Our findings suggest a dairy product pattern may reduce EC risk in Japanese men, especially smokers.

Background: Folate and other nutrients in the one-carbon metabolism pathway play essential roles in DNA synthesis and methylation, and may be critically involved in carcinogenesis. Low folate intake has been linked to the development of breast, colorectal and pancreatic cancer, and the effect may be modulated by other factors such as alcohol drinking and smoking. Up to date, few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer. Method: We examined the association between the intakes of folate, methionine, and vitamin B6 and B12 and gastric and esophageal cancer in the National Institutes of Health–AARP Diet and Health Study (492,293 men and women, aged 50 to 71 at baseline in 1995-1996). Dietary and supplemental intakes of such nutrients were assessed with a food frequency questionnaire at baseline. Total intake is a sum of dietary and supplemental intakes. Cancer cases were ascertained by linkage to state cancer registries. A multivariate Cox proportional hazard model was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: During an average of 9 years of follow up, we identified 815 and 935 incident cases of esophageal and gastric cancer, respectively. The median intake of dietary folate in the lowest (Q1), the middle (Q3) and the highest quintile (Q5) were 275, 405, and 595 mcg/d, respectively. Compared to Q3, Q1 of dietary folate intake was associated with a significantly higher risk of esophageal cancer (RR =1.33, 95% CI, 1.08, 1.64), while no further risk reduction was observed in Q5 (RR =1.01, 95% CI, 0.79, 1.28). The elevated risk in Q1 in relation to Q3 was more pronounced in esophageal squamous cell carcinoma (RR =1.91, 95% CI, 1.17, 3.10) than in esophageal adenocarcinoma (RR =1.22, 95% CI, 0.96, 1.54), and was observed across subgroups of alcohol consumption and smoking (RR (95% CI): 1.49 (0.95, 2.33) in nondrinkers, 1.25 (0.91, 1.72) in drinkers of &amp;gt;0-15 g/d of alcohol consumption, and 1.33 (0.92, 1.91) in drinkers of &amp;gt;15 g/d; and 1.29 (0.76, 2.18) in never smokers and 1.29 (1.02, 1.63) in ever smokers). Among other nutrients, low dietary intake of vitamin B6 was also associated with increased risk of esophageal cancer (Q1 vs. Q3: RR =1.30, 95% CI, 1.05, 1.61), and gastric cancer (Q1 vs. Q3: RR =1.22, 95% CI, 0.99, 1.50). There was a similar L-shaped association between esophageal cancer and total intake of folate and vitamin B6. No association was observed with methionine or vitamin B12. Conclusion: Our findings suggest that low intake of folate and vitamin B6 was associated with increased risk of esophageal cancer while higher intake of these nutrients did not provide additional benefits. Citation Format: Qian Xiao, Jiansong Ren, Christian Abnet, Yikyung Park. Intakes of folate, methionine, and vitamin B6 and B12 and risk of esophageal and gastric cancer in a large cohort study. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A105.

Background: Several studies have examined association between human papillomaviruses (HPV) and esophageal cancer, but results have been inconsistent. This is the first prospective study to investigate associations between α, β and γ HPV detection in the oral cavity and risk of esophageal cancer.Methods: We conducted a nested case-control study among 96,650 cancer-free participants in the American Cancer Society Cancer Prevention Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident esophageal cancer cases (n = 125) were identified during an average 3.9 years of follow-up. Three controls per case (n = 372) were selected and matched on age, sex, race/ethnicity, and time since mouthwash collection. α, β, and γ HPV DNA in oral samples were detected using a next-generation sequencing assay. Conditional logistic regression models were used to estimate OR and 95% confidence intervals (CIs), adjusting for smoking and alcohol consumption. Statistical significance was evaluated using permutation test.Results: Prevalence of oral α, β, and γ HPV was 18.4%, 64.8%, and 42.4% in cases and 14.3%, 55.1%, and 33.6% in controls, respectively. Oral HPV16 detection was not associated with esophageal cancer (OR = 0.54, 95% CI, 0.1-4.84) and none of the esophageal squamous cell carcinoma cases (n = 28) were HPV16 positive. Some oral HPV types were more common in cases than controls; however, none of the associations were statistically significant.Conclusions: Although HPVs in the oral cavity are very common, this study showed no evidence of association between oral HPVs and esophageal cancer.Impact: Oral HPVs may not contribute to risk of esophageal cancer. Cancer Epidemiol Biomarkers Prev; 27(10); 1168-75. ©2018 AACR.

Covering the Cover

The authors evaluated associations between occupational exposures in the textile industry and the risks of esophageal cancer and stomach cancer. The authors conducted a case-cohort study nested in a cohort of female textile workers in Shanghai, China. One hundred and two workers with incident esophageal cancer and 646 workers with incident stomach cancer diagnosed between 1989 and 1998 were compared with an age-stratified reference subcohort (n = 3,188). Work histories were ascertained for all study subjects from factory personnel records or interviews. Exposures were reconstructed for chemicals and dusts by linking work history data with a job-exposure matrix developed for the Shanghai textile industry. Hazard ratios and 95 percent confidence intervals were calculated with Cox proportional hazards modeling adapted for the case-cohort design. Risk of esophageal cancer was associated with long-term (> or = 10 years) exposure to silica dust (hazard ratio = 15.8, 95% confidence interval: 3.5, 70.6) and metals (hazard ratio = 3.7, 95% confidence interval: 1.9, 7.1). Cumulative exposure to endotoxin, a contaminant of cotton dust, was inversely related to risks of both esophageal cancer (p-trend = 0.01) and stomach cancer (p-trend < 0.001) when exposures were lagged 20 years. Endotoxin has not been previously reported to be a protective factor for either stomach cancer or esophageal cancer and therefore warrants further study.

AIMTo assess the relationship between serum levels of insulin-like growth factor-1 (IGF1)/IGF-binding protein-3 (IGFBP3) and the risk of esophageal carcinoma.METHODSWe assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective, nested case-control study of participants from the Japan Collaborative Cohort Study. A baseline survey was conducted from 1988 to 1990. Of the 110585 enrolled participants, 35% donated blood samples. Those who had been diagnosed with esophageal cancer were considered cases for nested case-control studies. A conditional logistic model was used to estimate odds ratios for the incidence of esophageal cancer associated with serum IGF1 and IGFBP3 levels.RESULTSThirty-one cases and 86 controls were eligible for the present assessment. The molar ratio of IGF1/IGFBP3, which represents the free and active form of IGF1, was not correlated with the risk of esophageal carcinoma. A higher molar difference between IGFBP3 and IGF1, which estimates the free form of IGFBP3, was associated with a decreased risk of esophageal carcinoma (P = 0.0146), and people in the highest tertile had the lowest risk (OR = 0.107, 95%CI: 0.017-0.669). After adjustment for body mass index, tobacco use, and alcohol intake, the molar difference of IGFBP3-IGF1 was inversely correlated with the risk of esophageal carcinoma (P = 0.0150).CONCLUSIONThe free form of IGFBP3, which is estimated by this molar difference, may be inversely associated with esophageal cancer incidence.

We conducted a systematic review and meta-analysis of meat intake and esophageal cancer risk, with subgroup analyses based on meat type and histological type of cancer. The purpose of this study was to investigate the association between meat intake and risk of esophageal cancer. We searched MEDLINE, EMBASE and Cochrane Library (April 2013) for cohort and case-control studies that assessed meat intake and esophageal cancer risk. Random-effect or fixed-effect models were used to pool relative risks (RRs) from individual studies with heterogeneity and publication bias analyses carried out. Seven cohort and 28 case-control studies were included. The summary RRs for esophageal cancer for the highest versus lowest consumption categories were 1.19 (95 % confidence interval [CI] 0.98-1.46) for total meat, 1.55 (95 % CI 1.22-1.96) for red meat, 1.33 (95 % CI 1.04-1.69) for processed meat, 0.72 (95 % CI 0.60-0.86) for white meat, 0.83 (95 % CI 0.72-0.96) for poultry, and 0.95 (95 % CI 0.76-1.19) for fish. When striated by histological subtype, positive associations were seen among esophageal squamous cell carcinoma and red meat, white meat and poultry, and esophageal adenocarcinoma with total meat and processed meat. Meat consumption is associated with esophageal cancer risk, which depends on meat type and histological type of esophageal cancer. High intake of red meat and low intake of poultry are associated with an increased risk of esophageal squamous cell carcinoma. High meat intake, especially processed meat, is likely to increase esophageal adenocarcinoma risk. And fish consumption may not be associated with incidence of esophageal cancer.

Aim: to systematise the data of available studies related to the association of papillomavirus infection with oesophageal squamous cell cancer. Methods. A literature search was conducted in PubMed and Google Scholar databases. All full-text articles from 1995 to 2023 were included. The language of the studies was not a barrier to inclusion in this meta-analysis. A total of 130 literature sources were analysed. The meta-analysis was based on data from 17 case-control studies, which together account for 1912 oesophageal squamous cell tumour tissue samples and 2206 control samples of normal oesophageal tissue. Key points. There is a growing body of research on the importance of human papillomavirus as a risk factor for oesophageal squamous cell cancer. However, the association of human papillomavirus with the risk of oesophageal cancer, despite the large number of studies on this topic, is still controversial. Conclusions. The resulting relative risk (RR) of oesophageal squamous cell cancer in papillomavirus infection was 1.22 (95% confidence interval (95% CI): 1.11–1.35; p = 0.000023). Meanwhile, stratification of the data according to the ethnicity of the patients showed that the highest risk of oesophageal squamous cell cancer in papillomavirus infection was observed in patients of Asian ethnic group (RR = 1.34; 95% C: 1.26–1.42; p = 0.042). In the Arab ethnic group, the risk of oesophageal squamous cell cancer with papillomavirus infection was 1.27 (95% CI: 1.09–1.48; p = 0.005), while in Europeans it does not reach statistically significant values (p = 0.232).

There is conflicting evidence on the association between folate intake and the risk of upper gastrointestinal tract cancers. In order to further elucidate this relationship, we performed a systematic review and quantitative meta-analysis of folate intake and the risk of esophageal, gastric, and pancreatic cancer. Four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) were searched to July 26, 2013, with no language restrictions for observational studies that measured folate intake and the risk of esophageal cancer, gastric cancer, or pancreatic cancer. Pooled odds ratios and 95% confidence intervals were calculated using a random effects model. The meta-analysis of dietary folate and esophageal cancer risk comprising of nine retrospective studies showed a decreased risk of esophageal cancer (odds ratio [OR] 0.59; 95% confidence interval [95% CI] 0.51-0.69). The meta-analysis of dietary folate and gastric cancer risk comprising of 16 studies showed no association (OR 0.94; 95% CI 0.78-1.14). The meta-analysis of dietary folate and pancreatic cancer risk comprising of eight studies showed a decreased risk of pancreatic cancer (OR 0.66; 95% CI 0.49-0.89). Dietary folate intake is associated with a decreased risk of esophageal and pancreatic cancer, but not gastric cancer. Interpretation of these relationships is complicated by significant heterogeneity between studies when pooled, and by small numbers of studies available to analyze when stratification is performed to reduce heterogeneity.

Second primary cancer is prevalent in patients with head and neck cancer (HNC), for which esophagus and lung are the most usual sites, associated with an extremely poor prognosis. However, information regarding the actual risk of second primary esophageal or lung cancer in South-east Asia, the betel-quid chewing area, has been restricted to data from single-institutions. We have therefore conducted a population-based study to evaluate the incidence, risk, and developmental time of second esophageal or lung cancer in HNC patients. Standardized incidence ratios (SIRs) and cumulative incidences were calculated for second primary esophageal or lung cancer using a database from the Taiwan Cancer Registry that included 63,720 cases having an initial diagnosis of HNC. The risk of second esophageal cancer was increased in patients with oral/pharyngeal (SIR = 8.71, 95% CI 7.55-10.01) and laryngeal (SIR = 4.65, 95% CI 3.37-6.27) cancers, whereas second lung risk was increased in patients with laryngeal (SIR = 2.05, 95% CI 1.69-2.45) and oral/pharyngeal (SIR = 1.56, 95% CI 1.34-1.80) cancers. The risk excess was prominent for patients with a follow-up interval <5 years and a first primary cancer diagnosed at age <50. Nevertheless, patients with nasopharyngeal carcinoma were not associated with an excess risk in second esophageal or lung cancer. The present dataset provides definite evidence that there is a substantial excess risk of second primary esophageal or lung cancer for the index tumors of oral cavity, pharynx and larynx. The absence of risk excess found in nasopharyngeal carcinoma is also compatible with the existing knowledge that it might have an entirely distinctive etiology.

Background Diet may affect esophageal and gastric cancer risk, but associations have been inconsistent. Due to the complexity of the diet, studies of dietary patterns may elucidate the associations between diet and cancer better than studies of individual foods. Yet, studies evaluating the association between index-based dietary patterns and incident esophageal and gastric cancers have been sparse. Objectives We aimed to prospectively evaluate the association between two diet quality indices, the Healthy Eating Index-2005 (HEI-2005) and the alternate Mediterranean Diet Score (aMED), and risk of esophageal and gastric cancers in the United States. Methods In sum, 494,968 participants from the National Institutes of Health-AARP Diet and Health study completed a self-administered baseline food frequency questionnaire which was used to estimate scores for each index. Results During the follow-up (1995-2006), we documented 215 esophageal squamous cell carcinomas (ESCC), 633 esophageal adenocarcinomas (EAC), 453 gastric cardia adenocarcinomas, and 501 gastric noncardia adenocarcinomas. Higher scores in the HEI-2005, reflecting healthy eating patterns, were associated with a reduced risk of ESCC (the highest quintile compared to lowest: hazard ratio (HR) =0.51, 95% confidence interval (CI): 0.31-0.86, Ptrend =0.001), and EAC (HR=0.75, 95% CI: 0.57-0.98, Ptrend=0.01). We observed an inverse association of ESCC with higher diet quality as assessed by aMED, but not for EAC. No significant associations for gastric cardia or noncardia adenocarcinomas were found with either HEI-2005 or aMED. Conclusions In this prospective study, the HEI-2005 was inversely associated with risk of both ESCC and EAC, while the aMED was associated with reduced risk of ESCC, suggesting that adherence to dietary recommendations may help prevent esophageal cancer. Citation Format: Wen-qing Li, Yikyung Park, Jennifer W. Wu, Jian-song Ren, Alisa M. Goldstein, Philip R. Taylor, Albert R. Hollenbeck, Neal D. Freedman, Christian C. Abnet. Index-based dietary patterns and risk of esophageal cancer and gastric cancer in the NIH-AARP diet and health study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4805. doi:10.1158/1538-7445.AM2013-4805

The north-western region of China has a high incidence of oesophageal cancer. This study aimed to investigate whether the intake of food and beverage at high temperature is associated with the risk of oesophageal cancer among adults residing in this remote part of China. A case-control study was undertaken in Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China, between 2008 and 2009. Participants were 359 incident oesophageal cancer patients and 380 hospital-based controls. Information on temperature of food and beverage intake was obtained by face-to-face interview. Logistic regression analyses were performed to ascertain the association between intake temperature and the risk of oesophageal cancer. The oesophageal cancer patients consumed foods and beverages at higher temperatures than controls, p<0.001. High temperature of tea, water and food intake appeared to increase the risk of oesophageal cancer by more than two-fold, with adjusted odds ratio (95% confidence intervals) of 2.86 (1.73-4.72), 2.82 (1.78-4.47) and 2.26 (1.49-3.45), respectively. Intake of food and beverage at high temperature was positively associated with the incidence of oesophageal cancer in north-western China.