Risk Of Stomach Cancer Research Articles

Dietary flavonoid intake and risk of stomach and colorectal cancer

Stomach and colorectal cancers are common cancers and leading causes of cancer deaths. Because the alimentary tract can interact directly with dietary components, stomach and colorectal cancer may be closely related to dietary intake. We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30, 2012. Twenty-three studies out of 209 identified articles were finally selected for the analysis. Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies. Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio (OR) (95%CI) = 1.00 (0.90-1.11) and 1.07 (0.70-1.61), respectively]. Among flavonoid subclasses, the intake of flavonols, flavan-3-ols, anthocyanidins, and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR (95%CI) = 0.71 (0.63-0.81), 0.88 (0.79-0.97), 0.68 (0.56-0.82), and 0.72 (0.61-0.85), respectively]. A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR (95%CI) = 0.68 (0.46-0.99)]. In the summary estimates from case-control studies, all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk, whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies. The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design. There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer.

Intake of Soy Products and Other Foods and Gastric Cancer Risk: A Prospective Study

BackgroundGastric cancer, the most common cancer in the world, is affected by some foods or food groups. We examined the relationship between dietary intake and stomach cancer risk in the Korean Multi-Center Cancer Cohort (KMCC).MethodsThe KMCC included 19 688 Korean men and women who were enrolled from 1993 to 2004. Of those subjects, 9724 completed a brief 14-food frequency questionnaire at baseline. Through record linkage with the Korean Central Cancer Registry and National Death Certificate databases, we documented 166 gastric cancer cases as of December 31, 2008. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% CIs.ResultsFrequent intake of soybean/tofu was significantly associated with reduced risk of gastric cancer, after adjustment for age, sex, cigarette smoking, body mass index, alcohol consumption, and area of residence (P for trend = 0.036). We found a significant inverse association between soybean/tofu intake and gastric cancer risk among women (RR = 0.41, 95% CI: 0.22–0.78). Men with a high soybean/tofu intake had a lower risk of gastric cancer, but the reduction was not statistically significant (RR = 0.77, 95% CI: 0.52–1.13). There was no interaction between soybean/tofu intake and cigarette smoking in relation to gastric cancer risk (P for interaction = 0.268).ConclusionsFrequent soybean/tofu intake was associated with lower risk of gastric cancer.

Increased Risk of Gastrointestinal Malignancy in Patients with Diabetes Mellitus and Correlations with Anti-Diabetes Drugs: A Nationwide Population-based Study in Taiwan

Although the major cause of morbidity and mortality in patients with diabetes mellitus (DM) is cardiovascular disease, DM is also associated with certain site-specific cancers. However, whether DM is associated with an increased risk of cancer of the digestive tract remains undetermined. A nationwide, population-based database in Taiwan was analyzed to explore the relationship between DM and cancer of the digestive organs. From 2000 to 2007, a study cohort consisting of 39,515 patients with newly diagnosed diabetes without a previous diagnosis of gastrointestinal (GI) cancer was identified from the National Health Insurance Research Database in Taiwan. A control cohort of 79,030 age- and sex-matched non-diabetic subjects was selected to compare the occurrence of GI malignancies between the two groups. The association between the incidence of GI cancers and the use of glucose-lowering therapies was also investigated. During the 7-year follow-up period, GI cancers developed in 929 diabetic patients (2.35%) and 1,126 subjects (1.42%) in the comparison cohort. DM was associated with a 2.75-fold (95% confidence interval (CI), 2.51-3.02) higher risk of developing GI malignancy. Among GI cancers, the incidences of stomach (adjusted hazard ratio (HR), 1.49; 95% CI, 1.16-1.92), liver (adjusted HR, 2.65; 95% CI, 2.29-3.07), colon (adjusted HR, 1.58; 95% CI, 1.28-1.94) and pancreatic cancers (adjusted HR, 4.35; 95% CI, 2.93-6.47) were significantly increased in the patients with DM. An analysis of the effects of various glucose-lowering therapies in the diabetic patients revealed the use of α-glucosidase inhibitors to be associated with a lower risk of hepatic cancer (adjusted HR, 0.62; 95% CI, 0.4-0.94). Thiazolidinedione (TZD) treatment was associated with lower stomach (adjusted HR, 0.11; 95% CI, 0.02-0.82) and hepatic cancer risks (adjusted HR, 0.46; 95% CI, 0.29-0.73), while sulfonylurea use was associated with a lower colon cancer risk (adjusted HR, 0.74; 95% CI, 0.51-1.09) and a higher pancreatic cancer risk (adjusted HR, 2.36; 95% CI, 1.21-4.61). Patients with DM have an increased risk of GI malignancy that may be affected by the use of different categories of glucose-lowering therapies.

Effect of nutrition education on knowledge of nutrition in relation to prevention of stomach cancer among undergraduates in south-west, Nigeria

Stomach cancer is one of the common cancers worldwide including developing countries and is identified as one of the most lethal among the diet related cancers. In Nigeria, there is paucity of data and information about the prevalence of stomach cancer and without doubt this disease is on the increase. Youth engage in the consumption of western diets which have been identified in the literature as one factor that is closely associated with cancers. This shift to western diets by most youth may be due to lack of nutritional knowledge on the health consequences of their eating habits. In years to come, there may be an increase in the incidence of diet -related cancers and other chronic diseases if nutrition education is not put in place especially among the youth. Not many studies in Nigeria have focused on nutrition education of the youth in relation to the prevention of chronic diseases ; prominent among which is stomach cancer. This study is aimed at providing nutrition related education to university undergraduates in order to create awareness about nutrition with a view to preventing a rise in the incidence of stomach cancer and other chronic diseases. A quasi -experimental design was used for this study. Multi -stage sampling was used to select 436 male and female undergraduates between 16 -25 years old from two universities in south- west Nigeria (one control and one experimental ). The intervention consisted of lectures on nutritional factors of stomach cancer one hour weekly for 8 weeks and a placebo lecture on HIV/AIDS stigmatization for the control group. A validated self -structured questionnaire was used to collect the data for the pretest and posttest . Demographic characteristics were analyzed with percentages; variables were analyzed using t -test and ANCOVA set at 95% confidence interval. Nutrition education improved knowledge of nutrition in the participants (p<0.00). The experimental group displayed higher nutrition knowledge compared to control . Level of study affected participants’ nutrition knowledge; students of lower level study performed better (p< 0.00). Gender also affected participants’ nutrition knowledge; females performed better than males (p<0.00). More nutrition education should be encouraged in school setting s to improve knowledge of nutrition in order to prevent a possible dietary risk of stomach cancer and other chronic diseases.

Diverging breast and stomach cancer incidence and survival in migrants in The Netherlands, 1996–2009

Background. Migrant populations usually experience a health transition with respect to their cancer risk as a result from environmental changes and acculturation processes. We investigated potentially contrasting experiences with breast and stomach cancer risk and survival in migrants to the Netherlands in a retrospective cohort study. Methods. Invasive breast (n = 96 126) and stomach cancer cases (n = 24 496) diagnosed 1996–2009 were selected from the population-based Netherlands Cancer Registry. Standardized Incidence Ratios (SIRs) were computed as the ratio of observed and expected cancers. Differences in survival were expressed as relative excess risk of mortality (RER). Results. Women from Morocco, Suriname and Turkey exhibited a significantly lower risk for breast cancer than native Dutch women (SIR range 0.5–0.9). Relative excess mortality was significantly increased in Surinamese (RER = 1.2, 95% CI 1.0–1.5) patients. The incidence of non-cardia stomach cancer was significantly elevated in all migrants, except in Indonesians, being highest in Turkish males (SIR = 2.2, 1.9–2.6). Cardia stomach cancer appeared to be less frequent in all migrants, being lowest in Surinamese males (SIR = 0.3, 0.2–0.5). Relative excess mortality was significantly lower in patients from the Antilles (RER = 0.7, 0.5–1.0), Suriname (0.8, 0.6–0.9) and Turkey (0.7, 0.6–0.9). Conclusion. The lower incidence rates of breast and cardia stomach cancer in migrants as well as their higher non-cardia stomach cancer rates reflect most likely early life exposures including pregnancy and/or dietary patterns during life-course. While higher relative excess mortality from breast cancer in migrant women might point toward inadequate access and treatment in this group, lower excess mortality from (especially non-cardia) stomach cancer remains to be explained.

Haldane, Hot Dogs and Halitosis: The Anion Nitrite As an Intrinsic Hypoxic Signaling Molecule and New Therapy for Pulmonary Arterial Hypertension

Nitrate and nitrite have traditionally been considered dietary toxins that increase the risk of stomach cancer. In this lecture we discuss how the scientific discovery was made that nitrate and nitrite are in fact natural signaling pathways in the human body. Nitrite is now considered a biological reservoir of nitric oxide (NO), present in plasma, red cells and organ systems, that is reduced to NO during physiological and pathological hypoxia. Current studies by multiple research groups indicate that dietary and NOS-dependent nitrite formation may contribute to critical physiological functions such as blood pressure control, hypoxic vasodilation, mitochondrial respiration and the cellular resilience to ischemic stress. Recent studies suggest that a number of cellular enzymes regulate nitrite reduction to NO at different oxygen tensions, with organ system specificity. The role of molybdenum containing enzymes and heme-globin superfamily proteins - hemoglobin, myoglobin, neuroglobin, cytoglobin and the plant and drosophila hemoglobins - are the subject of active current study, and recent advances in this area of investigation will be reviewed. Studies of cytochrome C oxidase, neuroglobin and plant hemoglobins have identified a role for heme coordination in the control of nitrite reduction to NO (six-to-five coordinate regulation of nitrite binding and reduction). New pre-clinical and clinical studies suggest that inhaled and oral nitrite may be able to prevent and reverse established pulmonary arterial hypertension and phase II proof of concept trials are currently in progress in the US and Europe. It is proposed that the nitrate - nitrite - NO pathway represents a fundamentally conserved pathway for energetics and signaling in biology.

Dust exposure and the risk of cancer in cement industry workers in Korea

Cement is used widely in the construction industry, though it contains hazardous chemicals such as hexavalent chromium. Several epidemiological studies have examined the association between cement dust exposure and cancer, but these associations have proved inconclusive. In the present study, we examined the association between dust exposure and cancer in cement industry workers in Korea. Our cohort consisted of 1,324 men who worked at two Portland cement manufacturing factories between 1997 and 2005. We calculated cumulative dust exposures, then categorized workers into high and low dust exposure groups. Cancer cases were identified between 1997 and 2005 by linking with the national cancer registry. Standardized incidence ratios (SIRs) were calculated for all workers and the high and low dust exposure groups, respectively. The SIR for overall cancers in all workers was increased (1.35, 95% CI: 1.01-1.78). The SIR for stomach cancer in the high dust exposure group was increased (2.18, 95% CI: 1.19-3.65), but there was no increased stomach cancer risk in the low dust exposure group. The SIR for rectal cancer in all workers was increased (3.05, 95% CI: 1.32-6.02). Rectal cancer risk was similar in the high and low exposure groups. Our findings suggest a potential association between exposure in the cement industry and an increased risk of stomach and rectal cancers. However, due to the small number of cases, this association should be further investigated in a study with a longer follow-up period and adjustment for confounders.

Genetic Polymorphism of Glutathione S-transferases M1 and T1, Tobacco Habits and Risk of Stomach Cancer in Mizoram, India

The incidence of stomach cancer in Mizoram is highest in India. We have conducted a population based matched case-control study to identify environmental and genetic risk factors in this geographical area. A total of 102 histologically confirmed stomach cancer cases and 204 matched healthy population controls were recruited. GSTM1 and GSTT1 genotypes were determined by PCR and H. pylori infections were determined by ELISA. Tobacco-smoking was found to be an important risk factor for high incidence of stomach cancer in Mizoram. Meiziol (local cigarette) smoking was a more important risk factor than other tobacco related habits. Cigarette, tuibur (tobacco smoke infused water) and betel nut consumption synergistically increased the risk of stomach cancer. Polymorphisms of GSTM1 and GSTT1 genes were not found to be directly associated with stomach cancer in Mizoram. However, they appeared to be effect modifiers. Persons habituated with tobacco smoking and/or tuibur habit had increased risk of stomach cancer if they carried the GSTM1 null genotype and GSTT1 non-null genotype. Tobacco smoking, especially meiziol is the important risk factor for stomach cancer in Mizoram. GSTM1 and GSTT1 genes modify the effect of tobacco habits. This study is a first step in understanding the epidemiology of stomach cancer in Mizoram, India.

Iodine Supplementation and Monitoring to Ensure Patient Health and Safety

Iodine deficiency is a leading cause of thyroid disorders. Deficiency can manifest as hypothyroidism, goiter, or impaired mental function. Insufficient levels of iodine increase the risk of thyroid cancer and may be associated with risk of breast, ovarian, endometrial, stomach, and esophageal cancer. In an effort to address iodine deficiency, salt iodization was introduced. Yet, despite these efforts, iodine levels have decreased in recent years. Several tests may be used to determine iodine status including the iodine spot test, iodine loading test, bromide spot test, bromide loading test, fluoride spot test, fluoride loading test and sodium/iodide symporter (NIS) test. Iodine supplements are effective in preventing and treating iodine deficiency and in achieving whole-body iodine sufficiency. In order to avoid adverse effects such as hyperthyroidism, and goiter, iodine supplementation requires proper monitoring of thyroid hormones (TSH, serum total T4, and free T3), with more frequent assessments during the first year of supplementation. Adverse effects are usually avoided when adequate and regular monitoring of thyroid hormone levels and whole-body iodine levels is employed and when dosages are increased/decreased accordingly.

Primary biliary cirrhosis and cancer risk: A systematic review and meta-analysis

Several studies have indicated that primary biliary cirrhosis (PBC) may be associated with increased risk of some cancers, but the results are controversial. We conducted a systematic review of studies to examine the association of PBC with cancer risk by meta-analysis. We searched the PubMed and EMBASE databases for English-language studies published before November 2011. Studies were included if they reported relative risk estimates with 95% confidence intervals (CIs) or related data for the association between PBC and cancer risk. Approximately 16,300 PBC patients from several countries were included in this analysis. Of the 3510 titles identified, 16 publications involving 17 studies meeting the inclusion criteria were included in the meta-analysis. Compared with the general population, PBC patients had a significantly higher risk of overall cancer (pooled rate ratio [RR], 1.55; 95% CI, 1.28-1.83) and hepatocellular carcinoma (HCC) (pooled RR, 18.80; 95% CI, 10.81-26.79). For stomach and pancreas cancers, the results of one study that only examined male patients with PBC indicated that PBC patients had increased risk of stomach cancer and pancreatic cancer, whereas the results of other studies of mixed-sex patients showed no significant association. Therefore, despite inconsistent results, the meta-analysis could not be conducted for assessing the association. PBC was not significantly associated with increased risk of other cancers. The present systematic review and meta-analysis demonstrate that PBC is closely associated with a greater risk of overall cancer and HCC, but not with other cancers. The data regarding the association between PBC and risks of several cancers need to be further confirmed in future studies.

Nutrition deficiency increases the risk of stomach cancer mortality.

BackgroundThe purpose of the study is to determine whether exposure to malnutrition during early life is associated with increased risk of stomach cancer in later life.MethodsThe design protocol included analyzing the trend of gastric cancer mortality and nutrition and evaluating the association between nutrient deficiency in early life and the risk of gastric cancer by hierarchical age–period–birth cohort (APC) analysis using general log-linear Poisson models and to compare the difference between birth cohorts who were exposed to the 1959–1961 Chinese famine and those who were not exposed to the famine. Data on stomach cancer mortality from 1970 to 2009 and the dietary patterns from 1955 to 1985 which included the 1959–1961 Chinese famine period in the Zhaoyuan County population were obtained. The nutrition information was collected 15 years prior to the mortality data as based on the latest reference of disease incubation.ResultsAPC analysis revealed that severe nutrition deficiency during early life may increase the risk of stomach cancer. Compared with the 1960–1964 birth cohort, the risk for stomach cancer in all birth cohorts from 1900 to 1959 significantly increased; compared with the 1970–1974 cohort, the risk for stomach cancer in the 1975–1979 cohort significantly increased, whereas the others had a steadily decreased risk; compared with 85–89 age group in the 2005–2009 death survey, the ORs decreased with younger age and reached significant levels for the 50–54 age group after adjusting the confounding factors. The 1930 to 1964 group (exposed to famine) had a higher mortality rate than the 1965 to 1999 group (not exposed to famine). For males, the relative risk (RR) was 2.39 and the 95% confidence interval (CI) was 1.51 to 3.77. For females, RR was 1.64 and 95% CI was 1.02 to 2.62.ConclusionThe results of the present study suggested that prolonged malnutrition during early life may increase the risk of stomach cancer mortality in later life.

Malignant Gastrocolic Fistula as a Late Complication of Radiation Therapy

Malignant gastrocolic fistula is a rare mode of presentation of gastric or colonic carcinoma [1–3]. A benign aetiology is more common, including peptic ulcer disease, particularly benign gastric ulcers which may relate to non-steroidal antiinflammatory use. Other benign causes include inflammatory bowel disease, post-PEG insertion, post-gastroenterostomy, pancreatitis, abdominal tuberculosis, trauma, perforated diverticular disease and infections including CMV, histoplasmosis, actinomycosis, amoebiasis, echinococcosis and lymphogranuloma venereum [2, 4–7]. A malignant gastrocolic fistula is most commonly found between the greater curvature of the stomach and the distal half of the transverse colon [8]. They are usually seen in the setting of large infiltrative tumours with a surrounding inflammatory reaction, and lymph node involvement is uncommon [8]. The colon rather than the stomach is the more usual site of origin. In a review of 1,500 cases of stomach cancer and 3,200 cases of colon cancer at the Lahey Clinic, 11 cases of gastrocolic fistula were reported, with 10 being of colonic origin [9]. Radiation therapy is associated with an increased risk of second cancers. Abdominal radiation therapy has been most frequently administered in the context of testicular cancer, where the overall cure rate is greater than 90 % [10]. The average age of presentation of testicular cancer is 35, and second neoplasms are uncommon but well-recognised complications where radiation therapy has been given [11–14]. Exposure to radiation may induce a broad variety of DNA damage including singleand double-stranded DNA breaks, cross-linking and damage to nucleotide bases [15]. Radiation-related genomic instability enhances the rate at which mutations and epigenetic changes are acquired in the descendants of that cell line after many generations of replication. In a cohort study of 40, 576 survivors of testicular cancer, Travis et al. reported on 2,285 second solid tumours observed where 1,619 new cancers were expected, demonstrating an elevated relative risk (ERR) as well as an excess absolute risk of developing a second neoplasm in comparison with the general population [16]. A further report of 5,142 patients treated with radiation therapy describes a 3.4fold increased risk of stomach cancer in survivors of testicular cancer and Hodgkin’s lymphoma [17]. This study found that the risk of second cancer begins approximately 10– 15 years after the original cancer diagnosis. We report herein a case of an adenocarcinoma presenting acutely as a J. Costelloe : C. O’Connell :O. Mc Cormack :N. Ravi : J. V. Reynolds Department of Surgery, St. James’s Hospital, Dublin, Ireland

A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy(-1) of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

Oral Insulin Secretagogues, Insulin, and Cancer Risk in Type 2 Diabetes Mellitus

Hyperinsulinemia might be the mechanism leading to an increased cancer risk in patients with type 2 diabetes. The objective was to evaluate the association between oral insulin secretagogues, insulins, and cancer incidence. A total of 108,920 patients with newly diagnosed type 2 diabetes were identified from the Taiwan National Health Insurance claims database during the period from 1 January 2000 to 31 December 2000. As of 31 December 2007, patients with incident cancer were included as cases, and up to four age- and sex-matched controls were selected by risk-set sampling. Logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between antidiabetic medication and cancer incidence. A total of 8,194 incident cancer cases and 32,776 diabetic controls were included. A significantly increased risk for overall cancer incidence was found for any use of insulin (OR, 1.97; 95% CI, 1.85-2.09) and glinides (OR, 1.16; 95% CI, 1.06-1.28). Significantly increased risks were found for first- and second-generation sulfonylureas (OR, 1.08; 95% CI, 1.01-1.15), but not for third-generation drug, glimepiride (OR, 1.00; 95% CI, 0.93-1.08). Use of insulin and glinides was associated with higher risks for liver, colorectal, lung, stomach, and pancreas cancer, whereas sulfonylurea was mainly associated with an increased risk of liver cancer. The results showed that sulfonylureas and glinides increased the risk for overall cancer, but to a lesser extent than insulin. Therapies that are associated with cancer risks certainly require further investigation.

The Association between Cancer Incidence and Family Income: Analysis of Korean National Health Insurance Cancer Registration Data

Economic status is known to be directly or indirectly related to cancer incidence since it affects accessibility to health-related social resources, preventive medical checkups, and lifestyle. This study investigates the relationship between cancer incidence and family income in Korea. Using the Korean National Health Insurance cancer registration data in 2009, the relationship between their family income class and cancer risk was analyzed. The age-standardized incidence rates of the major cancers were calculated for men and women separately. After adjusting for age, residential area, and number of family members, cancer risks for major cancers according to family income class were estimated using a logistic regression model. In men, the risk of stomach cancer for Income Class 5 (lowest) was 1.12 times (95% CI 1.02-1.23) higher than that of Income Class 1 (highest), for lung cancer 1.61 times (95% CI 1.43- 1.81) higher, for liver cancer 1.22 times (95% CI 1.08-1.37) higher, and for rectal cancer 1.37 times higher (95% CI 1.18-1.59). In women, the risk of stomach cancer for Income Class 5 was 1.22 times higher (95% CI 1.08-1.37) than that for Income Class 1, while for cervical cancer it was 2.47 times higher (95% CI 2.08- 2.94). In contrast, in men, Income Class 1 showed a higher risk of thyroid cancer and prostate cancer than that of Income Class 5, while, in women the same was the case for thyroid cancer. The results show the relationship between family income and cancer risk differs according to type of cancer.

Methyl bromide exposure and cancer risk in the Agricultural Health Study

Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects. We used Poisson regression to calculate rate ratios (RR) and 95% confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score. A total of 7,814 applicators (14.6%) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR=1.42; 95% CI, 0.51-3.95 and RR=3.13; 95% CI, 1.25-7.80 for low and high use compared with no use; p (trend)=0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a nonsignificant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance. Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.

Mo1565 Helicobacter pylori Infection and Development of Gastric Cancer a 10-Year Follow-up Population-Based Study in a High Incidence Area

Backgrounds & Aim: H. pylori (HP) infection is the most important etiology of gastric cancer (GC) in the world but it causes GC in only a minority of those infected .Eradication of HP can decrease the development of GC only in the subgroup of HP infected subjects without precancerous lesions. Strategies of HP eradication is still not well defined in countries with high mortality rates secondary to GC with almost universal HP infection in adults. The aim of the present study was to investigate the predictors of GC in an adult population with almost universal HP infection in an area with highest rate of gastric cancer in the world. Methods: 1011 healthy subjects 40 years and older, permanent residents of Ardabil and Meshkinshahr districts in northwest Iran, were randomly selected and enrolled in an endoscopic screening study during 2000 to 2001 year. Data on demographics and potential risk factors were collected using a well-structured questionnaire. Upper gastrointestinal endoscopy with multiple biopsy sampling was performed to detect HP infection and endoscopic precancerous lesions.Participants have been followed up until 2011. During followup period data on the occurrence of GC, mortality, and cause of death were obtained from cancer and death registries, and when neccessary by direct contacting to participants, and their families. The cumulative incidence and person-time incidence rate were calculated. The effect of other risk factors in addition to H. pylori infection on the risk of GC development were estimated by fitting multivariate hazard model using Cox proportional regression analysis, and were presented as hazard ratio (HR) and corresponding 96% confidence interval (95%CI). Results: During 10-year follow up, 36 participants (3.6%) developed GC yielding an incidence rate of 3.6 per 1000 person-years. The significant risk factors of GC included age over 50 (HR 4.8; 95%CI 1.4-16.2), a positive family history of stomach cancer (6.4; 3.1-13.1), smoking (5.7; 2.5-12.6), gastric atrophy (2.3; 1.0-5.1), intestinal metaplasia (4.5; 2.3-8.9) and presence of gastric ulcer (4.8; 1.9-11.5). Joint presence of precancerous lesion and one of the other risk factors significantly increased risk of stomach cancer as (46.5; 10.8-98.6) for a positive family history of stomach cancer; (27.6; 6.5-116.4) for smoking and (25.1; 16.3-105.3) for age>50. Conclusion: Combining the information on family history, lifestyle risk factors and the type of precancerous lesion may be helpful in order to identify high risk HP infected patients who need more intensive surveillance for early detection of GC. Key words: Stomach cancer, Precancerous lesions, Risk factors, H. pylori, Ardabil,Iran.

Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach

Iron can cause oxidative stress and DNA damage, and heme iron can catalyze endogenous formation of N-nitroso compounds, which are potent carcinogens. Dietary iron promotes esophageal cancer incidence in animal studies and has been identified as a growth factor for Helicobacter pylori, an established risk factor for stomach cancer. We conducted a population-based case-control study of adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in Nebraska. Heme iron and total iron intake were estimated from a food frequency questionnaire and databases of heme and total iron. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for known risk factors. Esophageal cancer was positively associated with higher intakes of heme iron (ORQ4 vs. Q1=3.04, 95% CI: 1.20-7.72; P trend=0.009) and total iron from meat sources (ORQ4 vs. Q1=2.67, 95% CI: 0.99-7.16; P trend=0.050). Risk of stomach cancer was elevated among those with higher intakes of heme iron (ORQ4 vs.Q1=1.99, 95% CI: 1.00-3.95; P trend=0.17) and total iron from meat (OR=2.26, 95% CI: 1.14-4.46; P trend=0.11). Iron intake from all dietary sources was not significantly associated with risk of either cancer. Our results suggest that high intakes of heme and iron from meat may be important dietary risk factors for esophageal and stomach cancer and may partly explain associations with red meat.

Cancer Risks for the Relatives of Colorectal Cancer Cases with a Methylated MLH1 Promoter Region: Data from the Colorectal Cancer Family Registry

Methylation of the MLH1 gene promoter region is an underlying cause of colorectal cancer (CRC) with high microsatellite instability (MSI-H) diagnosed in persons without a germ line mutation in a mismatch repair (MMR) gene (non-Lynch Syndrome CRC). It is unclear whether relatives of CRC cases with MLH1 methylation have an increased risk of colorectal or other cancers. In this retrospective cohort study, we assessed risk of CRC and other cancers for the first- and second-degree relatives of CRC cases with a methylated MLH1 gene, by comparing observed numbers of cases with those expected on the basis of age-, sex-, and country-specific cancer incidences (standardized incidence ratios). The cohort consisted of 3,128 first- and second-degree relatives of the 233 MLH1-methylated CRC cases with no MMR or MUTYH gene mutations. The standardized incidence ratio (SIR) for CRC was 1.60 [95% confidence interval (CI), 1.22-2.16] for first-degree relatives and 1.08 (0.74-1.60) for second-degree relatives. The SIR for gastric cancer was 2.58 (1.52-4.71) for first-degree relatives and 4.52 (2.23-10.61) for second-degree relatives and, for ovarian cancer, it was 2.16 (1.29-3.86) for first-degree relatives. The risk of liver cancer was also increased significantly in first-degree relatives but the estimate was on the basis of only two cases. These data imply that relatives of CRC cases with MLH1 methylation may be at increased risk of CRC and stomach cancer and possibly ovarian and liver cancer, suggesting that there may be a heritable factor for CRC and other cancers associated with MLH1 methylation in non-Lynch syndrome CRCs.

Mutations and polymorphisms of genes moderate increase in gastric cancer risk

Results of studies performed in our center point at DNA changes of many cancer (mostly moderate) susceptibility genes. Association of weak mutations and polymorphism of many genes and additional influence of environmental factors can significantly increase the risk of cancer development. The preliminary studies performed in our department indicate, that increased risk of gastric cancer may be related to mutation in NOD2 and CHK2 genes predisposing to cancers of many organs. The CHEK2 gene encodes checkpoint kinase 2 (Chk2), it acts as a tumor suppressor whose functions are central to the induction of cell cycle arrest and apoptosis by DNA damage. Results of studies performed in our center indicate that the frequency of the IVS2+1G→A alteration was significantly increased in a group of 658 consecutive patients, especially in those under 50 years of age (OR=5.332, p=0.0174). I157T was over-represented in the group of familial gastric cancer patients, particularly in patients diagnosed at less than 50 years of age (OR=3.687, p=0.0011) and females. The specific group of intestinal and mixed histopathological subtype occurs more frequently (OR=1.671) in consecutive carriers of I157T mutation. Recently, the NOD2/CARD15, gene located on chromosome 16q12, has been associated with Crohn’s disease. It is believed to play a role both in intracellular recognition of lipopolysaccharides (LPS) typical of Gram negative bacteria and subsequent activation of NFkB. 3020insC NOD2 mutation causes an increased risk of developing chronic inflammatory diseases of the gastrointestinal tract and colorectal cancer in their course. In light of recent studies, in fact 3020insC mutation predisposes to cancers of many organs, including breast, ovarian, lung. Studies conducted in our center in the group of 103 patients with a family history of gastric cancer, have shown that NOD2 3020insC carriers in persons over 50 y of age more than doubled (OR=2.479, p=0.022) and among women almost 3-fold increased risk. In addition, NOD2 R702W alteration occurred almost three times more frequently (OR=2.816, p=0.0121) in the group of 241 consecutive patients with gastric cancer diagnosed before 50 years of age and over 2-times frequently (OR=2.268, p=0.0371) in gastric cancer selected histopathologically as intestinal type according to Lauren. There are a large number of reports describing the relationship between changes in the gene TP53, particularly polimomorfizm Arg72Pro, and risk of gastric cancer. Many researchers have found links between gene polymorphism of Interleukin-1, and the risk of stomach cancer. Gene polymorphism of angiotensin converting enzyme ACE, was recently linked with the pathogenesis and development of human cancers. Research Ebert MP, et al. conducted in a group of 88 patients shows that the insertion / deletion ACE gene may be associated with the development of early gastric cancer in the German population. In the Japanese population genetically distant, however, found no relationship between gastric cancer and ACE gene polymorphism). Sentences on the ACE polymorphism and risk of stomach cancer researchers are divided among different centers. XRCC1 gene is part of composite protein complex containing the s-polymerase DNA ligase I and PARP (polymerase poly (ADP-ribose). This multi-unit complex is involved in DNA repair pathway. T. Poplawski et al. indicate that the variant Gln / Gln XRCC1 gene polymorphism Arg399Gly occurred more frequently in patients with gastric cancer and family burden (OR=2.04, 95% CI=1,27-3,29) and the results obtained from studies in the group of 152 patients with a family history of gastric cancer suggest that gene XRCC1 399Gln allele may be considered a marker of gastric cancer. In terms of predisposition to gastric cancer has also been studied recently LAPTM4B gene associated with a genetic predisposition to liver cancer, having LAPTM4B alleles * 1 and LAPTM4B * 2. The risk of stomach cancer was increased 1.819 times in patients with genotype * 1 / 2 (CI=1.273-2.601) and 2.387 times in patients with genotype * 2 / 2 LAPTM4B (CI=1.195-4.767) compared with genotype * 1 / first. These studies indicate that allele * 2 LAPTM4B may be one of the genetic factors of gastric cancer. Further studies of newly described mutation moderately increased risk of stomach cancer may allow to estimate the real risk of gastric cancer associated with these mutations in the Polish population.