Gastric Cardia Adenocarcinoma Research Articles

Detection and Clinical Significance of Lymph Node Micrometastasis in Gastric Cardia Adenocarcinoma

Lymph node micro metastasis was investigated in gastric cardia adenocarcinoma (GCA) patients without lymph node metastasis on routine pathological examination. The relationship between micrometastasis and clinicopathological features was also evaluated. A total of 349 lymph nodes were obtained from 45 patients with GCA. Micrometastases were detected by immunohistochemical staining for the markers cytokeratin 19 (CK19) and CD44 variant 6 (CD44v6). A total of 33 lymph nodes (9.5%) from 15 patients (33.3%) were positive for CK19. Of these, 27 lymph nodes (7.7%) from 12 patients (26.7%) were also positive for CD44v6. Micrometastasis was significantly related to depth of tumour invasion and Lauren classification (intestinal or diffuse). The recurrence rate was significantly higher and 2-year survival rate significantly lower in patients with than in those without lymph node micrometastasis, showing the necessity of detecting micrometastasis in GCA patients who test negative for lymph node metastasis on routine examination. CK19 and CD44v6 were shown to be good markers for micrometastasis detection.

Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH‐AARP diet and health study

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995-1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27-2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84-1.64) p for trend = 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37-2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91-1.78) p for trend = 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5-<25 kg/m(2)) [HR (95% CI) 0.76 (0.63-0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96-1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90-1.05)]. p for interaction = 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI.

Diabetes and risk of esophageal and gastric adenocarcinomas.

Diabetes has been consistently associated with an increased risk of liver, pancreas and endometrial cancer and has been implicated as a risk factor for esophageal and gastric cancers, although this association has been less well studied. We sought to determine the role of diabetes in the etiology of esophageal, gastric cardia and distal gastric adenocarcinomas (DGAs). This analysis included patients with esophageal adenocarcinoma (EA) (n = 209), gastric cardia adenocarcinoma (GCA) (n = 257) and DGA (n = 382), and 1,309 control participants from a population-based case-control study conducted in Los Angeles County. The study included non-Hispanic whites, African Americans, Hispanics and Asian Americans. The association of diabetes with the three tumor types was estimated using polytomous logistic regression. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated. Nine percent of control participants and 13% of the case patients reported a history of diabetes. After adjustment for age, gender, race, birthplace, education, cigarette smoking status and body mass index, diabetes was associated with an increased risk of EA (OR, 1.48; 95% CI, 0.94-2.32; p = 0.089) and DGA (OR, 1.47; 95% CI, 1.01-2.15; p = 0.045), but was not associated with risk of GCA (OR, 0.96; 95% CI, 0.59-1.55; p = 0.87). However, the association between diabetes and risk of DGA was statistically significant only among patients for whom we interviewed their next of kin. Our study further investigated the association between diabetes and adenocarcinomas of the esophagus and distal stomach.

A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH–AARP Diet and Health Study

ObjectiveThe incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major...

Meta-analysis: risk of esophageal adenocarcinoma with medications which relax the lower esophageal sphincter

Reasons for the rising annual incidence of esophageal adenocarcinoma (EAC) remain uncertain. Previous studies have given conflicting results, but some have suggested that drugs which relax the lower esophageal sphincter (LES) may increase the risk of EAC. This study is to determine systematically the risk of EAC associated with individual medications which relax the LES and compare risks with esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). Relevant published studies were identified by systematic searching PubMed for case-control studies reporting on risk of EAC, ESCC or GCA with use of medications known to reduce LES pressure. Pooled odds ratios (ORs) were calculated for each malignancy. Data were analyzed from four case-control studies involving 9,412 participants. EAC was significantly associated with theophylline use (OR 1.55, 95% confidence interval [CI] 1.05-2.28; P= 0.03, I(2) = 0%) and anticholinergic medications (OR 1.66, 95% CI 1.13-2.44; P= 0.01, I(2) = 84%). This effect was not observed in cases of ESCC or GCA. Other drug groups including calcium channel modulators and nitrates did not increase the risk of EAC. An inverse relationship was observed between ESCC and nitrates and between GCA and benzodiazepines. The lack of increased EAC risk with many commonly used medications is reassuring. However, a significant correlation was found between EAC and the use of anticholinergics and theophyllines. This may reflect common causality between obstructive lung disease and EAC, and further studies to explore these relationships are warranted.

Abstract A59: Selenoprotein gene variants and risk of esophageal and gastric cancer in a Chinese population

Abstract Objectives: Observational studies and intervention trials suggest that selenium has potential cancer prevention properties. We previously found that selenium supplementation reduces cancer mortality, particularly gastric cancer mortality, in a high-risk region in China, and that low serum selenium concentration is associated with increased risks of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). In humans, selenium may exert chemopreventive actions through the 25 known selenoproteins, which contain residues of selenocysteine, the 21st amino acid. Therefore, genetic variants in selenoprotein genes may influence susceptibility to ESCC and GCA, yet no previous studies have comprehensively investigated these potential associations. Thus, we examined the association between genetic variants in selenoprotein and selenium metabolism genes and risks of ESCC and GCA. Methods: We included 1027 ESCC and 753 GCA cases plus 1452 controls from two epidemiologic studies in the high-risk region in China. We genotyped 272 tag single nucleotide polymorphisms (SNPs) in all 25 known selenoprotein genes and 4 selenium metabolism genes. For each gene, we calculated a standardized summary p-value using the adaptive rank truncated product (ARTP) method. For SNPs, logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: In gene-based tests, the selenoprotein gene SELS (selenoprotein S) was associated with ESCC risk (p=0.00070); TXNRD2 (thioredoxin reductase 2) showed borderline non-significant associations with both ESCC (p=0.063) and GCA (p=0.051). In SNP-based tests for these two genes, rs8029790 (tagged to SELS in the upstream noncoding region) was associated with a 1.30-fold increased risk of ESCC (CI=1.14, 1.47; p=0.000052), whereas rs2073750 (tagged to intron in TXNRD2) was associated with risks of both ESCC (OR=0.84, CI=0.74, 0.94; p=0.0029) and GCA (OR=0.82, CI=0.72, 0.93; p=0.0026). Conclusions: The potential anticarcinogenic properties of selenium may be due to its presence as the amino acid selenocysteine in human selenoproteins. The association of SNPs in selenoprotein genes SELS and TXNRD2 with ESCC and GCA risk suggests that selenium and these selenoproteins may play an important role in cancer development. Our findings warrant further research on elucidating the functional effects of these SNPs on selenoproteins in the context of upper gastrointestinal (UGI) carcinogenesis so that we can better understand the role of selenium supplementation in cancer prevention. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A59.

Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. In 1986, 120,852 Dutch men and women aged 55-69 filled out a questionnaire on diet and other cancer risk factors. After 16.3 years of follow-up, 101 ESCC, 144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Multivariable adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable consumption was nonsignificantly inversely associated with EAC and ESCC risk, but not with GCA and GNCA risk. Significant inverse associations were observed for raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI) 0.68-0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI 0.54-0.95). Total fruit consumption was associated with a nonsignificantly decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk (RRs for highest vs. lowest intake: 0.55, 95% CI 0.31-0.98 and 0.38, 95% CI 0.21-0.69, respectively). Specifically for current smokers, vegetables and possibly also fruits intake was inversely associated with ESCC and EAC risk. Consumption of (specific groups of) vegetables and fruits may protect against subtypes of esophageal and gastric cancer.

Risk factors for esophageal and gastric cancers in Shanxi Province, China: A case–control study

Objective: Smoking and alcohol consumption explain little of the risk for upper-gastrointestinal (UGI) cancer in China, where over half of all cases in the world occur. Methods: We evaluated questionnaire-based risk factors for UGI cancers in a case–control study from Shanxi Province, China, including 600 esophageal squamous cell carcinomas (ESCCs), 599 gastric cardia adenocarcinomas (GCAs), 316 gastric noncardia adenocarcinomas (GNCAs), and 1514 age- and gender-matched controls. Results: Ever smoking and ever use of any alcohol were not associated with risk of UGI cancer; only modest associations were observed between ESCC risk and highest cumulative smoking exposure, as well as GNCA risk and beer drinking. While several associations were noted for socioeconomic and some dietary variables with one or two UGI cancers, the strongest and most consistent relations for all three individual UGI cancers were observed for consumption of scalding hot foods (risk increased 150–219% for daily vs. never users) and fresh vegetables and fruits (risk decreased 48–70% for vegetables and 46–68% for fruits, respectively, for high vs. low quartiles). Conclusion: This study confirms the minor role of tobacco and alcohol in UGI cancers in this region, and highlights thermal damage as a leading etiologic factor.

P1-263 A prospective study of obesity and risk of oesophageal and gastric adenocarcinoma

Explanations for increasing rates of oesophageal adenocarcinoma (OAC) remain unclear, though the concurrent increase in the prevalence of obesity may be a partial explanation. Although obesity has emerged as a...

Association of polymorphisms in transforming growth factor-β receptors with susceptibility to gastric cardia adenocarcinoma

Both transforming growth factor-β receptor I (TGFBR1) and receptor II (TGFBR2) are serine/threonine kinases and play important roles in TGF-β/Smads signal pathway. The case-control study was performed to evaluate the possible association of Int7G24A and *6A polymorphisms of TGFBR1 and G-875A polymorphism of TGFBR2 with susceptibility to gastric cardia adenocarcinoma (GCA) in a population of North China. Polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR methods were used respectively to detect the genotype of Int7G24A, *6A and G-875A in 468 GCA and 584 healthy controls. Immunohistochemistry method was used to determine the protein expression of TGFBR1 and TGFBR2. Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing GCA. There were no differences in the genotype distribution of TGFBR1 *6A polymorphism among cases and controls. However, A allele of Int7G24A significantly elevated the risk of developing GCA (adjusted OR=1.34, 95% CI 1.03-1.87) and A allele of G-875A significantly decreased the risk of developing GCA (adjusted OR=0.73, 95% CI 0.49-0.92). When stratified for TNM stage, A allele of Int7G24A and G-875A allele carriers had a 1.41-fold (95% CI 1.05-1.98) increased and a 0.70-fold (95% CI 0.47-0.92) decreased risk of stage III and IV gastric cardia adenocarcinoma. The protein expression of TGFBR1 and TGFBR2 in GCA was not correlated with genotypes of them. In conclusions, TGFBR1 Int7G24A and TGFBR2 G-875A polymorphisms may play important roles in the risk of GCA in North China.

Smoking and COX-2 Functional Polymorphisms Interact to Increase the Risk of Gastric Cardia Adenocarcinoma in Chinese Population

BackgroundOver-expression and increased activity of cyclooxygenase (COX)-2 induced by smoking has been implicated in the development of cancer. This study aimed to explore the interaction between smoking and functional polymorphisms of COX-2 in modulation of gastric cardia adenocarcinoma (GCA) risk.Methods and FindingsThree COX-2 polymorphisms, including –1195G>A (rs689466), –765G>C (rs20417), and 587Gly>Arg (rs3218625), were genotyped in 357 GCA patients and 985 controls. In the multivariate logistic regression analysis, we found that the –1195AA, –765GC, and 587Arg/Arg genotypes were associated with increased risk of GCA (OR = 1.50, 95% CI = 1.05–2.13; OR = 2.06, 95% CI = 1.29–3.29 and OR = 1.67, 95% CI = 1.04–2.66, respectively). Haplotype association analysis showed that compared with G−1195-G−765- GGly587Arg, the A−1195-C−765-AGly587Arg conferred an increased risk of GCA (OR = 2.49, 95% CI = 1.54–4.01). Moreover, significant multiplicative interactions were observed between smoking and these three polymorphisms of –1195G>A, –765G>C, and 587Gly>Arg, even after correction by false discovery rate (FDR) method for multiple comparisons (FDR-P interaction = 0.006, 5.239×10−4 and 0.017, respectively). Similarly, haplotypes incorporating these three polymorphisms also showed significant interaction with smoking in the development of GCA (P for multiplicative interaction = 2.65×10−6).ConclusionThese findings indicated that the functional polymorphisms of COX-2, in interaction with smoking, may play a substantial role in the development of GCA.

Serum thyroglobulin, a biomarker for iodine deficiency, is not associated with increased risk of upper gastrointestinal cancers in a large Chinese cohort

Iodine concentrates in gastric tissue and may act as an antioxidant for the stomach. We previously showed that self-reported goiter was associated with significantly increased risk of gastric noncardia adenocarcinoma (GNCA) and nonsignificantly increased risks of gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) in a prospective case-cohort study in a high-risk population in China. Negatively correlated with iodine levels, serum thyroglobulin (Tg) is a more sensitive biomarker of iodine deficiency than goiter. Our study aimed to determine whether baseline serum Tg was also associated with development of GNCA, GCA and ESCC in the same cohort, the Linxian General Population Nutrition Intervention Trial. Sera from ∼200 subjects of each case type and 400 noncases were tested for serum Tg concentration using appropriate assays. Tg was modeled as sex- and assay-specific quartiles in Cox regression models adjusted for age, smoking, alcohol, Helicobacter pylori status, pepsinogens I/II ratio, family history and commune of residence. In the final combined analysis, participants in the highest quartile of serum Tg, compared to those in the lowest quartile, had adjusted hazard ratios of 0.88 (95% confidence interval 0.50-1.52), 1.14 (0.63-2.05) and 0.78 (0.47-1.31) for GNCA, GCA and ESCC, respectively. Using serum Tg, a sensitive biomarker of iodine deficiency, we found no association between serum Tg concentrations and risk of these upper gastrointestinal (UGI) cancers in the study population. Our results do not support the hypothesis that iodine deficiency, as assessed by serum Tg, is associated with an increased risk of UGI cancers.

Association between novel PLCE1variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck

BackgroundPhospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN.MethodsWe genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population.ResultsAlthough none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (Ptrend = 0.046), particularly for non-oropharyngeal tumors (Ptrend = 0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR = 1.29, 95% CI = 1.01-1.64; AG/GG vs. AA: adjusted OR = 1.30, 95% CI = 1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR = 0.54, 95% CI = 0.34-0.86; TG/GG vs. TT: adjusted OR = 0.76, 95% CI = 0.61-0.95).ConclusionsOur findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers.

Tobacco Smoking and Esophageal and Gastric Cardia Adenocarcinoma

Smoking has been related to esophageal and gastric cardia adenocarcinoma, but the magnitude of the association is uncertain. We conducted a meta-analysis of 33 studies published up to January 2010. We derived summary estimates using random-effects models. Compared with never-smokers, the pooled relative risk (RR) was 1.76 (95% confidence interval = 1.54-2.01) for ever-smokers, 2.32 (1.96-2.75) for current smokers, and 1.62 (1.40-1.87) for ex-smokers. There was no important difference between esophageal (RR = 1.85 for ever- vs. never-smokers) and gastric cardia (RR = 1.76) adenocarcinoma. We found a direct association with dose (RR = 2.48 [2.14-2.86] for ≥ 20 cigarettes/d) and duration (RR = 2.32 [1.92-2.82] for ≥ 40 years) of cigarette consumption. This meta-analysis estimates the excess of esophageal and gastric cardia adenocarcinoma risk for smokers. This risk was similar for the 2 cancer sites.

Prospective Study of Self-Reported Diabetes and Risk of Upper Gastrointestinal Cancers

Although gastric noncardia adenocarcinoma (GNCA) incidence rates in the United States have decreased, the rates of gastric cardia adenocarcinoma (GCA) and esophageal adenocarcinoma (EADC) have increased. Obesity increases the risks of GCA and EADC, and the associations may be partially mediated by insulin resistance. A few case-control studies have shown an association between diabetes and an increased risk of EADC. We prospectively examined the association between diabetes and upper gastrointestinal (UGI) cancers in a cohort of 469,448 people in the United States, ages 50 to 71 at baseline. Cox proportional hazards regression was used to estimate the HR and 95% CI for diabetes and UGI cancers, controlling for multiple potential confounders, including body mass index (BMI). We observed no association of self-reported diabetes with risk of EADC, HR (95% CI) = 0.98 (0.73-1.31), esophageal squamous cell carcinoma (ESCC), HR (95% CI) = 1.02 (0.60-1.74), or GNCA, HR (95% CI) = 0.98 (0.70-1.37). However, diabetes was significantly associated with an increased risk of GCA, HR (95% CI) = 1.89 (1.43-2.50). The significant association between diabetes and risk of GCA remained after adjustment for BMI, HR (95% CI) = 1.70 (1.28-2.26) and did not differ by BMI strata (P(interaction) = 0.83). The significant association was unchanged when restricting to only overweight subjects (BMI 25 to ≤30), HR (95% CI) = 1.83 (1.18-2.85). We found a significant association between self-reported diabetes and increased risk of GCA. Our results suggest that the metabolic and hormonal changes related to diabetes may play a role in the etiology of GCA independently from BMI.

Aberrant methylation of the CpG island of HLTF gene in gastric cardia adenocarcinoma and dysplasia

Objectives To investigate the promoter methylation of HLTF in the tissues and plasma of patients with gastric cardia adenocarcinoma (GCA) and dysplasia. Design and methods Nested MSP approach was used to detect HLTF methylation status. Results The frequency of HLTF methylation in high grade dysplasia and GCA tumor tissues was significantly higher than that in chronic inflammation tissues and was significantly associated with upper gastrointestinal cancers (UGIC) family history and protein and mRNA expression of the gene. HLTF methylation was not found in the plasma of patients with chronic inflammation and low grade dysplasia, while 4.0% (1/25) of patients with high grade dysplasia and 20.8% of (20/96) GCA patients were detected with hypermethylation of HLTF in the plasma. Conclusions In all, HLTF methylation may exist in gastric cardia dysplasia stages and may play important role in the development of GCA especially in individuals with UGIC family history.

Correlation of TSP1 G1678A and A2210G Polymorphisms to Risk of Gastric Cardia Adenocarcinoma

Objective To investigate the possible association of TSP1 exon10 G1678A and exon13 A2210G polymorphisms with susceptibility to gastric cardia adenocarcinoma(GCA) in a population of North China.Methods The TSP1 G1678A and A2210G single nucleotide polymorphisms(SNPs) were genotyped by polymerase-chain reaction-restriction fragment length polymorphism(PCR-RFLP) analysis in 145 GCA patients and 198 healthy controls.Results The overall genotype and allelotype distributions of TSP1 G1678A in GCA patients were not significantly different from those in healthy controls(P0.05).When stratified for smoking status and upper gastrointestinal cancers(UGIC) family history,compared with GG and GA genotype,AA genotype significantly increased the risk of developing GCA in non-smoker group [age and gender and UGIC family history adjusted odds ratio(OR)= 1.79,95%CI= 1.46~2.11].The frequency of G allelotype was less than 1%,which indicated that TSP1 A2210G was not a common polymorphism in north China.Conclusion AA genotype of TSP1 G1678A may be one of the factors that affect the risk of developing GCA in non-smoking population in north China.

Principal Component Analysis of Dietary and Lifestyle Patterns in Relation to Risk of Subtypes of Esophageal and Gastric Cancer

To carry out pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing gastroesophageal reflux disease (GERD)/body mass index (BMI) score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, whereas fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.

Genetic variants at 1q22 and 10q23 reproducibly associated with gastric cancer susceptibility in a Chinese population

Two recent genome-wide association studies reported significant associations of genetic variants at 1q22, 10q23 and 20p13 with gastric cancer (GC) risk in Chinese populations. However, these findings have not been confirmed in other independent studies. Here, we performed an independent case-control study in a Chinese population by genotyping three loci (rs4072037A>G at 1q22, rs2274223A>G at 10q23 and rs13042395C>T at 20p13) in 1681 GC cases and 1858 controls. We found that rs4072037 at 1q22 and rs2274223 at 10q23 were significantly associated with risk of GC with per allele odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.63-0.81; P = 2.98 × 10(-7)] and 1.42 (95% CI: 1.27-1.58; P = 9.68 × 10(-10)), respectively. The association was more prominent for rs2274223 in female (OR = 1.86, 95% CI: 1.49-2.32) and gastric cardia adenocarcinoma (GCA) (OR = 1.71, 95% CI: 1.49-1.95). Furthermore, we combined the two single-nucleotide polymorphisms to evaluate the joint effect and found that the GC risk significantly increased with the number of risk allele increasing with a trend P value of 6.66 × 10(-16), and individuals with four risk alleles had a 3.28-fold (95% CI: 1.75-6.13) risk of GC compared with those having no risk alleles. However, no significant association was detected between rs13042395 at 20p13 and GC risk (OR = 1.04, 95% CI: 0.94-1.15; P = 0.452). In conclusion, our results indicate that genetic variants at 1q22 and 10q23 but not 20p13 may serve as candidate markers for GC susceptibility in the Chinese population.

A Population-Based Analysis of Esophageal and Gastric Cardia Adenocarcinomas in Ontario, Canada: Incidence, Risk Factors, and Regional Variation

IntroductionIn Western countries, the incidence of esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) is increasing. This population-based study describes the incidence of, associated patient risk factors for, and regional variation in EA/GCA in Ontario, Canada. MethodsAll adults with a new diagnosis of EA or GCA between 1972 and 2005 in Ontario were identified. Adjusted annual incidence rates were calculated, and multivariate models were used to identify patient risk factors. Maps were created to explore regional variation. ResultsOver the study period, 8,245 persons were diagnosed with EA/CGA; incidence increased from 1.01 to 3.9 per 100,000. Age (>65 vs. <50 years; rate ratio (RR), 3.4; 95% confidence interval (CI), 2.8–4.1) and comorbidity (highest vs. lowest, RR, 3.5; 95% CI, 2.9–4.2) were most strongly associated with the development of EA/GCA. We found considerable regional variation in the rates of EA/GCA (North West vs. Central region, RR, 6.5; 95% CI, 4.4–9.6). Maps suggested ethnicity may explain some regional variation, and that the current allocation of designated surgical treatment centers for EA/CGA may be suboptimal. ConclusionsThe incidence of EA/GCA is rising dramatically in Ontario. Further investigation of observed regional variation is warranted, particularly for the allocation of cancer health resources.