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Background: Environmental tobacco smoke (ETS) exposure is hypothesized to influence survival after breast cancer, but few studies have examined this association. Methods: A population-based cohort of women (N = 1,508) diagnosed with first primary invasive or in situ breast cancer in 1996 to 1997 was interviewed shortly after diagnosis and again approximately 5 years later to assess ETS exposure, and women were followed for more than 18 years using the National Death Index; 597 deaths (237 associated with breast cancer) were identified. Multivariable Cox regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for mortality among women with breast cancer as related to at-diagnosis and at-/postdiagnosis changes in ETS exposure. Results: There was little or no association between at-diagnosis ETS exposure and all-cause (HR = 1.04; 95% CI, 0.78–1.40) or breast cancer–specific (HR = 0.98; 95% CI, 0.63–1.52) mortality. Mortality was elevated among women who reported cessation in postdiagnosis ETS exposure up to 1 year before the follow-up assessment, for all-cause (HR = 1.81; 95% CI, 0.87–3.74) and breast cancer mortality (HR = 1.89; 95% CI, 0.68–5.24); however, estimates were imprecise. Conclusions: We found little evidence of an association between at-diagnosis ETS exposure and mortality after breast cancer. Postdiagnosis cessation of ETS exposure was positively associated with mortality, although we could not rule out chance and reverse causation as possible explanations. Impact: Exposure to ETS does not appear to influence mortality after breast cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 278–80. ©2016 AACR.

Polychlorinated biphenyls (PCBs) are hypothesised to influence breast carcinogenesis due to their persistence and potential to induce oestrogenic and anti-oestrogenic effects. Whether PCBs influence survival following breast cancer is unknown.A population-based cohort of women diagnosed with first primary invasive or in situ breast cancer in 1996-1997 and with blood-measured PCBs (n=627) collected shortly after diagnosis was followed for vital status through 2011. After 5 and 15 years, we identified 54 and 187 deaths, respectively, of which 36 and 74 were breast cancer related. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality for baseline PCB concentrations, individually and as oestrogenic (ΣGroup 1B: PCB101, PCB174, PCB177, PCB187, and PCB199), anti-oestrogenic (ΣGroup 2A: PCB66, PCB74, PCB105, and PCB118; ΣGroup 2B: PCB138 and PCB170), and cytochrome P450 enzyme-inducing (ΣGroup 3: PCB99, PCB153, PCB180, PCB183, and PCB203) groups.The highest PCB174 tertile was associated with an increase in all-cause (HR=2.22, 95% CI: 1.14-4.30) and breast cancer-specific (HR=3.15, 95% CI: 1.23-8.09) mortalities within 5 years of diagnosis and remained associated with breast cancer-specific mortality (HR=1.88, 95% CI: 1.05-3.36) at 15 years. At 5 years, the highest tertile of PCB177 was positively associated with all-cause mortality (HR=2.12, 95% CI: 1.05-4.30). At 15 years, the highest tertiles of ΣGroup 2A congeners and PCB118 were inversely associated with all-cause mortality (HR=0.60, 95% CI: 0.39-0.83; HR=0.63, 95% CI: 0.43-0.92, respectively).In this first US study of PCBs and breast cancer survival, PCBs were associated with mortality in biologically plausible directions. The investigation of other, structurally similar, chemicals may be warranted.

Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up (N = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43-4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43-12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19-2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45-4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.

Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people; however, the etiology of these cancers is poorly understood. We therefore investigated associations of body mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux and use of nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (

Purpose Obesity is associated with increased bioavailability of estrogen, hyperinsulinemia, and chronic inflammation, all of which may promote tumor growth. Given DNA repair and oxidative stress pathways may work together with these mechanisms to influence carcinogenesis, we hypothesized that genetic variation in these pathways may modify the obesity-postmenopausal breast cancer (BC) association. Methods Resources from a population-based case-control study (990 cases and 970 controls) were used to construct logistic regression models. Body mass index (BMI, weight [kilogram]/height [square meter]) was assessed 1 year before reference date. We characterized interactions between BMI and 29 genetic polymorphisms in oxidative stress and DNA repair pathways. Results Age-adjusted odds ratios (95% confidence intervals) for postmenopausal BC were 1.24 (1.00–1.52) and 1.35 (1.09–1.71) for 25 ≥ BMI 2 , respectively. We observed multiplicative interactions ( P ≤ .05) for eight gene polymorphisms in DNA repair and oxidative stress pathways. For example, among MPO variant allele carriers, obesity was associated with a twofold increased risk of postmenopausal BC (2.13 [1.35–3.36]); however, in wild-type homozygotes, the relationship was less pronounced (1.33 [0.93–1.89]). Our findings were no longer significant after Bonferroni correction. Conclusions Obesity may be particularly deleterious for postmenopausal BC development in the presence of biologically plausible DNA repair or oxidative stress genotypes.

Polycyclic aromatic hydrocarbon (PAH)–DNA adducts have been associated with breast cancer incidence. Aberrant changes in DNA methylation may be an early event in carcinogenesis. However, possible relations between PAH–DNA adducts, methylation, and breast cancer are unknown. The objectives of this study were to (1) assess associations between PAH–DNA adducts, and breast cancer, stratified by DNA methylation markers and (2) examine interactions between adducts and DNA methylation in association with breast cancer and tumor subtype. In a population-based case–control study, promoter methylation of 13 breast cancer-related genes was measured in tumor tissue (n = 765–851 cases). Blood DNA from breast cancer cases (n = 873) and controls (n = 941) was used to assess PAH–DNA adducts and global methylation. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95 % confidence intervals (CI); and the ratio of the OR (ROR) was used to assess heterogeneity. Women with detectable PAH–DNA adducts and methylated RARβ (ROR 2.69, 95 % CI 1.02–7.12; p for interaction = 0.03) or APC (ROR 1.76, 95 % CI 0.87–3.58; p for interaction = 0.09) genes were more likely to have hormone receptor-positive tumors than other subtypes. Interactions with other methylation markers were not apparent (p ≥ 0.10). The association between adducts and breast cancer did not vary by methylation status of the tumor nor did adducts associate with global methylation in the controls. Gene-specific methylation of RARβ, and perhaps APC, may interact with PAH–DNA adducts to increase risk of hormone receptor-positive breast cancer. There was little evidence that adducts were associated with or interacted with other methylation markers of interest.

Purpose Although risk factors for squamous cell carcinoma of the esophagus and adenocarcinomas of the esophagus (EA), gastric cardia (GC), and other (noncardia) gastric (OG) sites have been identified, little is known about interactions among risk factors. We sought to examine interactions of diet, other lifestyle, and medical factors with risks of subtypes of esophageal and gastric cancers. Methods We used classification tree analysis to analyze data from a population-based case-control study (1095 cases, 687 controls) conducted in Connecticut, New Jersey, and western Washington State. Results Frequency of reported gastroesophageal reflux disease symptoms was the most important risk stratification factor for EA, GC, and OG, with dietary factors (EA, OG), smoking (EA, GC), wine intake (GC, OG), age (OG), and income (OG) appearing to modify the risk of these cancer sites. For esophageal squamous cell carcinoma, smoking was the most important risk stratification factor, with gastroesophageal reflux disease, income, race, noncitrus fruit, and energy intakes further modifying risk. Conclusion Various combinations of risk factors appear to interact to affect risk of each cancer subtype. Replication of these data mining analyses are required before suggesting causal pathways; however, the classification tree results are useful in partitioning risk and mapping multilevel interactions among risk variables.

The associations of types of fish and fish preparation methods with pancreatic cancer risk remain unknown. The authors conducted a prospective cohort study in western Washington State among 66,616 adults, aged 50-76 years, who participated in the VITamins And Lifestyle cohort study. Diet was assessed by a food frequency questionnaire. Pancreatic cancer cases were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. During an average follow-up of 6.8 years, 151 participants developed pancreatic cancer (adenocarcinoma). Long-chain (n-3) polyunsaturated fatty acids (LC-PUFAs) and nonfried fish intake were inversely associated with pancreatic cancer incidence. When the highest and lowest tertiles of exposure were compared, the multivariable-adjusted hazard ratio of pancreatic cancer was 0.62 (95% confidence interval: 0.40, 0.98) (P(trend) = 0.08) for LC-PUFAs and 0.55 (95% confidence interval: 0.34, 0.88) (P(trend) = 0.045) for nonfried fish. Docosahexaenoic acid showed a greater inverse association with pancreatic cancer than eicosapentaenoic acid. No statistically significant associations were observed with fried fish and shellfish consumption. The potential health impact of fish consumption may depend on the types of fish consumed and fish preparation methods. LC-PUFAs, particularly docosahexaenoic acid, and nonfried fish, but not shellfish or fried fish, may be beneficial in the primary prevention of pancreatic cancer.

Diabetes has been associated with increased risk of breast cancer in a number of epidemiologic studies, but its effects on survival among women diagnosed with breast cancer have been examined less frequently. Importantly, prior investigations have rarely considered the influence of factors associated with diabetes such as obesity, age at diabetes diagnosis, duration of diabetes, or diabetes treatments.We evaluated the effect of self-reported diabetes on breast cancer incidence and mortality in the Long Island Breast Cancer Study Project, which includes 1,447 breast cancer cases and 1,453 controls. Follow-up data for all-cause (n = 395) and 5-year breast cancer-specific mortality (n = 104) through December 2005 were determined for case women from the National Death Index. Adjusted logistic regression and Cox proportional hazards models were used to estimate odds ratios (OR) and hazards ratios (HR), respectively.Postmenopausal women with diabetes were at increased risk of developing breast cancer [OR = 1.35; 95 % confidence interval (CI) = 0.99-1.85], as were those who were not of white race regardless of menopausal status [OR = 3.89; 95 % CI = 1.66-9.11]. Among case women, diabetes was associated with a modestly increased risk of death from all causes [HR = 1.65; 95 % CI = 1.18-2.29], an association that was stronger in women who were obese at breast cancer diagnosis [HR = 2.49; 94 % CI = 1.58-3.93]. In analyses restricted to diabetics, there was no statistically significant effect of duration of diabetes or type of treatment on breast cancer incidence or mortality.Our findings suggest that diabetes may increase incidence of breast cancer in older women and non-whites, and mortality due to all causes.

Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case–control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these potential associations.

Abnormal methylation in gene promoters is a hallmark of the cancer genome; however, factors that may influence promoter methylation have not been well elucidated. As the one-carbon metabolism pathway provides the universal methyl donor for methylation reactions, perturbation of this pathway might influence DNA methylation and, ultimately, affect gene functions. Utilizing approximately 800 breast cancer tumor tissues from a large population-based study, we investigated the relationships between dietary and genetic factors involved in the one-carbon metabolism pathway and promoter methylation of a panel of 13 breast cancer-related genes. We found that CCND2, HIN1 and CHD1 were the most "dietary sensitive" genes, as methylation of their promoters was associated with intakes of at least two out of the eight dietary methyl factors examined. On the other hand, some micronutrients (i.e., B 2 and B 6) were more "epigenetically active" as their intake levels correlated with promoter methylation status in 3 out of the 13 breast cancer genes evaluated. Both positive (hypermethylation) and inverse (hypomethylation) associations with high micronutrient intake were observed. Unlike what we saw for dietary factors, we did not observe any clear patterns between one-carbon genetic polymorphisms and the promoter methylation status of the genes examined. Our results provide preliminary evidence that one-carbon metabolism may have the capacity to influence the breast cancer epigenome. Given that epigenetic alterations are thought to occur early in cancer development and are potentially reversible, dietary modifications may offer promising venues for cancer intervention and prevention.

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP -2548AA genotype when compared to the LEP -2548GG genotype (age-adjusted OR = 1.30; 95% CI = 1.01-1.66). This association was stronger among postmenopausal women who were obese (OR = 1.86; 95% CI = 0.95-3.64) although the interaction was of borderline statistical significance (P = 0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time = 66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.

A number of risk factors for esophageal and gastric cancers have emerged, yet little is known whether risk factors map to molecular tumor markers such as overexpression of the tumor suppressor TP53. Using a US multicenter, population-based case-control study (170 cases of esophageal adenocarcinomas, 147 gastric cardia adenocarcinomas, 220 non-cardia gastric adenocarcinomas, and 112 esophageal squamous cell carcinomas), we examined whether the risk associated with cigarette smoking, body mass index (BMI), gastroesophageal reflux disease (GERD), and non-steroidal anti-inflammatory drug (NSAID) use varied by P53 overexpression. We defined P53 overexpression through immunohistochemistry of paraffin-embedded tumor tissues, using cutpoints based on percent of cells positive. Polytomous logistic regression was used to assess differences between each case group (defined by tumor subtype and P53 expression) and the control group by risk factors. The proportion of cases overexpressing P53 by tumor subtype was 72% for esophageal adenocarcinoma, 69% for gastric cardia adenocarcinoma, 52% for non-cardia gastric adenocarcinoma, and 67% for esophageal squamous cell carcinoma. For most tumor subtypes, we found little difference in risk factors by tumor P53 overexpression. For non-cardia gastric cancer however, an association with cigarette smoking was suggested for tumors that do not overexpress P53, whereas larger BMI was related to adenocarcinomas that overexpress P53 versus no overexpression. Overall, this study did not find a clear relationship between P53 protein overexpression and the known risk factors for subtypes of esophageal and gastric cancers. Further research on these tumors is needed to identify molecular markers associated with variations in the risk factor profiles.

Choline is an essential nutrient required for methyl group metabolism, but its role in carcinogenesis and tumor progression is not well understood. By utilizing a population-based study of 1508 cases and 1556 controls, we investigated the associations of dietary intake of choline and two related micronutrients, methionine and betaine, and risk of breast cancer. The highest quintile of choline consumption was associated with a lower risk of breast cancer [odds ratio (OR): 0.76; 95% confidence interval (CI): 0.58−1.00] compared with the lowest quintile. Two putatively functional single nucleotide polymorphisms of cholinemetabolizing genes, PEMT −774G>C (rs12325817) and CHDH +432G>T (rs12676), were also found be related to breast cancer risk. Compared with the PEMT GG genotype, the variant CC genotype was associated with an increased risk of breast cancer (OR: 1.30; 95% CI: 1.01−1.67). The CHDH minor T allele was also associated with an increased risk (OR: 1.19; 95% CI: 1.00−1.41) compared with the major G allele. The BHMT rs3733890 polymorphism was also examined but was found not to be associated with breast cancer risk. We observed a significant interaction between dietary betaine intake and the PEMT rs7926 polymorphism (Pinteraction=0.04). Our findings suggest that choline metabolism may play an important role in breast cancer etiology.—Xu, X., Gammon, M. D., Zeisel, S. H., Lee, Y. L., Wetmur, J. G., Teitelbaum, S. L., Bradshaw, P. T., Neugut, A. I., Santella, R. M., Chen, J. Choline metabolism and risk of breast cancer in a population-based study.

Background: Polymorphisms in glutathione-S-transferase ( GST ), N-acetyltransferase ( NAT ) 1 , and CYP1A1 genes have been suggested as susceptibility factors for esophageal and gastric adenocarcinomas, but have not been consistently linked to elevated risks. In a population-based case–control study, we examined risks in relation to polymorphisms of the following genes: GSTP1 ; GSTM1 ; GSTT1 ; NAT1 ; and CYP1A1 . Methods: Histologically confirmed incident cases, ages 30–79, were identified in three US locations. Population controls from the same catchment areas were frequency matched to expected age and sex distributions of esophageal and gastric cardia adenocarcinomas. DNA was extracted from buffy coat for PCR-based assays, with interpretable genotyping results obtained from 209 controls, 67 esophageal adenocarcinomas, 60 gastric cardia adenocarcinomas, and 56 noncardia gastric adenocarcinomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated among whites, adjusting for age, sex, and study center. Results: In all histologic subgroups, ORs were somewhat elevated for the GSTP1 Val/Val genotype (versus Ile/Ile ), although 95% CIs included 1.00. The respective ORs for esophageal, cardia, and other gastric adenocarcinomas were 1.73 (0.75–4.02), 1.46 (0.57–3.73), and 1.22 (0.48–3.09). No consistent patterns of elevated risk were associated with the null GSTM1 or GSTT1 genotypes, one or two copies of NAT1*10 or *11 alleles, or CYP1A1 Val/Val or Ile/Val genotypes (versus Ile/Ile ). Conclusions: Additional research in larger samples is needed to further assess polymorphisms and their interactions with epidemiologic risk factors, particularly for esophageal adenocarcinoma, which has been increasing markedly in incidence.

Objectives; We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case–control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model. Methods; Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects’ homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH–DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station. Results; The data for soil, PAH–DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40–80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection

Background & Aims: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1β and its endogenous receptor antagonist are associated with risk of Helicobacter pylori -related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. Methods: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Results: Proinflammatory genotypes of tumor necrosis factor α and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B o IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6–5.1) for one, 5.4 (2.7–10.6) for 2, and 27.3 (7.4–99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were not associated with any of the cancers studied. Conclusions: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.