Family History Of Stomach Cancer Research Articles

Socio-economic factors and medical conditions affecting regular stomach cancer screening in Korea: a retrospective longitudinal study using national public health data for 11 years

ObjectiveThis study aimed to explore socio-economic factors and medical conditions that affect regular stomach cancer (SC) screening among Korean adults. Study designThis was a retrospective observational study. MethodsStudy subjects were 5545 adults aged ≥40 years who participated in the 2007–2012 Korean National Health and Nutrition Examination Survey and were followed up to year 2017 based on data linking to the Korean National Health Insurance Service and Korean Health Insurance Review and Assessment. Socio-economic factors included sex, age, residential area, education, occupation, marital status, disability, public and private health insurance, service through local public health organizations, history of cancer except for SC, and family history of SC. Medical factors included six gastric lesions with the possibility of facilitating SC screening, including benign gastric neoplasm, chronic atrophic gastritis, gastric polyp, Helicobacter pylori infection, intestinal metaplasia, and peptic ulcers. The outcome was adherence to SC screening, which was divided into non-adherence, irregular adherence, and regular adherence. ResultsAfter adjusting for the effects of socio-economic factors, multivariate ordinal logistic regression revealed that participants with a history of four types of gastric lesions were more likely to regularly participate in SC screening: chronic atrophic gastritis (odds ratio [OR] 1.567; 95% confidence interval [CI] = 1.276–1.923), gastric polyps (OR 1.565; 95% CI = 1.223–2.003), H. pylori infection (OR 1.637; 95% CI = 1.338–2.003), and peptic ulcer (OR 2.226; 95% CI 1.750–2.831). ConclusionsTo improve participation in SC screening, it is necessary to implement personalized strategies for individuals at risk for gastric cancer in addition to population-based strategies for vulnerable groups.

Biomarkers for predicting diabetes in gastric cancer patients with machine learning methods based on proteomic data

Gastric cancer is a type of cancer that occurs when cells in the stomach tissue grow and multiply abnormally. Gastric cancer usually starts in the inner layer of the stomach wall and can spread to other layers over time. This type of cancer is most common in people over the age of 50, but it can also occur in younger people. Symptoms of gastric cancer include indigestion and stomach pain, nausea and vomiting, loss of appetite and weight loss, bloody stools, fatigue and weakness. Although the exact cause of stomach cancer is not known, several risk factors have been identified. These risk factors include infection with the bacterium Helicobacter pylori, a family history of stomach cancer, consumption of excessively salty foods, smoking, heavy alcohol use and some genetic factors. Diabetes, on the other hand, is a hormonal disorder that regulates the body's blood sugar levels. Normally, an organ called the pancreas controls blood sugar by producing a hormone called insulin. Insulin helps glucose (sugar) enter the cells so that they can make energy. In diabetes, this regulation is disrupted, which can lead to high blood sugar and various health problems. The relationship between stomach cancer and diabetes is not yet fully understood. In this study, machine learning models (Stochastic Gradient Boosting, Bagged Classification and Regression Trees) based on proteomic data were used to predict the diabetes risk of 40 gastric cancer patients, 21 with DM and 19 with non-DM. Performance metrics for the optimal model (Stochastic Gradient Boosting) the accuracy, balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value and F1-score values are 0.86, 0.83, 0.67, 1.00, 1.00, 0.80, 0.80, respectively. According to the variable importance values obtained as a result of the model, Mucin-13 protein has a positive predictive value in predicting the diabetes risk of gastric cancer patients in the clinic.

Stomach cancer burden in China: Epidemiology and prevention.

In 2020, stomach cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide. Due to the relatively huge population base and the poor survival rate, stomach cancer is still a threat in China, and accounts for nearly half of the cases worldwide. Fortunately, in China, the incidence and mortality rates of stomach cancer presented a declining trend owing to the change of individual life styles and the persistent efforts to prevent stomach cancer from the governments at all levels. Helicobacter pylori (H. pylori) infection, poor eating habits, smoking, history of gastrointestinal disorders, and family history of stomach cancer are the main risk factors for stomach cancer in China. As a result, by taking risk factors for stomach cancer into account, specific preventive measures, such as eradicating H. pylori and implementing stomach cancer screening projects, should be taken to better prevent and decrease the burden of stomach cancer.

GASTRIC ADENOCARCINOMA MASQUERADING AS CHRONIC COUGH

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Chronic cough in adults is defined by cough lasting for at least eight weeks in duration. It remains one of the most common symptoms encountered in ambulatory care, largely attributed to Upper Airway Cough Syndrome (UACS), Asthma, Non-asthmatic Eosinophilic Bronchitis (NAEB), or Gastroesophageal Reflux Disease (GERD). Other less common etiologies shouldn't be overlooked, such as those disorders which stimulate cough receptors. These receptors are located throughout the body including the gastrointestinal tract;irritation of any of these can trigger the vagal-mediated afferent limb of the cough reflex arc. We present the case of a patient with gastric cancer with an initial complaint of three months of cough with associated dyspnea. CASE PRESENTATION: A 33-year-old male with a medical history of obstructive sleep apnea, prior tobacco use, and GERD presented with a three month history of dry cough, fatigue, and dyspnea. Previous primary care visits were conducted via telehealth amid the COVID-19 pandemic, where he was empirically treated with therapies for UACS, asthma, and reflux disease without improvement. His physical exam and chest radiograph were unremarkable. Pulmonary function tests were not obtained secondary to profound coughing with forced exhalation maneuvers. On further questioning, he endorsed early satiety, 10-pound weight loss, and a family history of stomach cancer. CT of the chest demonstrated questionable gastric thickening, retroperitoneal lymphadenopathy surrounding the mesenteric root, a nine millimeter lytic lucency along the right periphery of the 11th thoracic vertebral body, and subtle diffuse peripheral tree-in-bud pulmonary opacities. Bronchoscopy with lavage, brushings, and endobronchial biopsies were negative for infection, granulomas, or malignancy. Upper endoscopy revealed a laterally spreading lesion with central ulceration in the gastric cardia, with biopsy consistent with poorly differentiated gastric adenocarcinoma. Stage IV disease was confirmed by retroperitoneal lymph node sampling. DISCUSSION: Gastric cancer represents 1.4% of all new cancer cases annually in the U.S., most frequently in the sixth decade of life in those with multiple risk factors. Our patient presented nearly three decades earlier with a chronic cough which is exceedingly rare. Plausible risk factors for our patient include male sex, Hispanic ethnicity, obesity, prior tobacco use, and familial predisposition. Early symptoms are equivocal but usually include abdominal pain and weight loss. Respiratory symptoms generally portend late-stage metastasis to the lungs or pulmonary embolism, which our patient did not exhibit. CONCLUSIONS: While UACS, Asthma, NAEB, and GERD remain the most conceivable etiologies of chronic cough, fully investigating all red flag symptoms during patient encounters, with consideration of uncommon causes, endure as foundational tenets of chronic cough evaluation. REFERENCE #1: Irwin RS, French CL, Chang AB, Altman KW, CHEST Expert Cough Panel*. Classification of cough as a symptom in adults and management algorithms: chest guideline and expert panel report. Chest. 2018;153(1):196-209. REFERENCE #2: Kou A, Patel JK, Adetula I, Frunzi J. Gastric cancer presenting as persistent pneumonia: an unusual case report. Cureus. Published online March 21, 2021. REFERENCE #3: Polverino M, Polverino F, Fasolino M, Ando F, Alfieri A, De Blasio F. Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip Respir Med. 2012;7(1):5. DISCLOSURES: No relevant relationships by Patrick Kicker, source=Web Response No relevant relationships by Ashley Soler Acevedo, source=Web Response

Assessment of the Factors Contributing to Gastric Carcinoma among Patients at Baghdad Educational Hospitals

BACKGROUND: Stomach cancer refers to any malignant neoplasm that arises from the region extending between the gastro esophageal junction and the pylorus. Approximately 95 % of stomach tumors are epithelial in origin and designated as adenocarcinomas. Adeno-squamous, squamous, and undifferentiated carcinomas are however rare (1). Aim of the study: Assessment of the factors contributing to gastric carcinoma among patients at Baghdad educational hospitals. METHODOLOGY: A descriptive design of study was carried out from the period of 1st October 2015 until, the end of May 2016, to a purposive random sample consist of (30) patients with gastric carcinoma. The instrument questionnaire tool consist of two parts, First part consist of (8) items & second part consist of (12) items. The study was conducted in (4) setting; Digestive system teaching hospital, Al-Emamain teaching hospital, Al kindy teaching hospital and Baghdad teaching hospital. The data have been analyzed through the application of: descriptive and the inferential analysis, and the researcher used the SPSS version 20 to analysis of data. RESULTS: the characteristics of present study were male, their age group was 50 - 59 year old most of them were married. The study indicated that patients with changes factors complained of (using too many anti-inflammatory, stress and anxiety, complaining of stomach ulcers, high consumption of hot food or spicy and salty food, and consuming junk food). Smoker or patients with diabetes, hypertension, heart disease and cancer were at high risk and a large proportion of them had no family history of stomach cancer, while other factors (such as working with chemicals in places related to health hazards such as rubber and coal, or patients with overweight, or alcohol consumption) were low risk. CONCLUSION: The study concluded that the risk factors among patients with gastric cancer more common age group of (50 to 59) years old and the study showed that risk factors among patients with gastric cancer are associated significantly more frequently with low educational level. RECOMMENDATION: The study recommends coordination with specialists from the Ministry of Health to establish centers for cancer of the stomach for the early detection of cancer and treatment and for the purpose of follow-up and equipped with all new technological machinery to examine cancer and motivate further studies in this aspect.

Exploring the Excluded Territory: A Case of Signet Cell Cancer of the Excluded Stomach

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight reduction surgeries. Evaluation of diseases of the excluded stomach such as ulcers or malignancy pose a significant challenge due to difficulty in accessing the excluded portion of stomach. We report a case of gastric cancer of the excluded stomach diagnosed using advanced endoscopy techniques. A 40-year-old female with Roux-en-Y gastric bypass surgery performed 13 years ago for morbid obesity presented with epigastric pain and weight loss. She was recently diagnosed with bilateral metastatic signet cell carcinoma of the ovaries for which she was on chemotherapy. Her family history was significant for gastric cancer in maternal aunt. Abdominal computerized tomography (CT) was unremarkable. Esophagoduodenoscopy failed to examine the excluded stomach due to limited length of scope and was otherwise normal. Colonoscopy was unremarkable. The excluded stomach was subsequently approached using antegrade double balloon enteroscopy (ADBE) via afferent limb of Roux-en-Y bypass. A large infiltrative ulcerated circumferential mass was found in the prepyloric region and antrum of the stomach. Biopsies were negative for H. pylori infection and revealed invasive signet cell gastric adenocarcinoma that likely had metastasized to the ovaries. Gastric cancer is the fifth most common malignancy worldwide and the fourth leading cause of cancer-related deaths. RYGB is associated with a 4-fold reduction in incidence of gastric cancer in animal models. Tinoco et al reported the incidence of gastric cancer in the excluded stomach to be 0.03% among 3047 patients who underwent bariatric surgery. However, larger prospective studies are lacking regarding incidence of cancer in this population. Risk factors for gastric cancer include H. pylori infection, smoking, high-salt intake, family history of stomach cancer, obesity and a diet low in fruits and vegetables. Symptoms are non-specific like anorexia, epigastric pain, anemia and weight loss following a period of stability or weight gain. Minimal invasive techniques which can be used to evaluate the excluded stomach are ADBE, percutaneous endoscopy, virtual gastroduodenoscopy, laparoscopic transgastric endoscopy and endoscopic ultrasound (EUS). Patients with prior RYGB presenting with alarming, new onset, unexplained symptoms should prompt evaluation including adequate visualization of the excluded stomach with imaging and advanced endoscopic techniques.Figure: showing postoperative anatomy of modern RYGB.Figure: showing endoscopic view of Infiltrative ulcerated mass in prepyloric region and antrum of stomach (black arrow).Figure: Histopathology slide showing signet cell gastric adenocarcinoma (black arrow).

A Novel Endoscopic Technique to Diagnose Gastric Cancer in the Excluded Stomach After Roux-en-Y Gastric Bypass

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight reduction surgeries. Evaluation of diseases of the excluded stomach (Figure 1) such as ulcers or malignancy pose a significant challenge due to difficulty in accessing the excluded portion of the stomach. We report the first case of the gastric cancer of the excluded stomach diagnosed with endoscopic ultrasound (EUS). A 50-year-old female with Roux-en-Y gastric bypass surgery performed six years ago presented with epigastric pain, nausea and recurrent gastrointestinal bleeding for nine months. Multiple upper and lower gastrointestinal (GI) endoscopies, as well as a video capsule endoscopy failed to identify the source of her recurrent bleeding. Abdominal computed tomography (CT) scan showed a mass in the excluded stomach with enlarged lymph nodes in the perigastric region and gastrohepatic ligament. An EUS via gastric pouch showed diffuse wall thickening of the excluded stomach at the antrum (Figure 2) and two enlarged lymph nodes in the gastrohepatic ligament. Fine needle aspiration (FNA) of the lymph nodes and the gastric wall of the excluded stomach revealed poorly differentiated gastric adenocarcinoma (Figure 3). The biopsy was negative for H. pylori infection. Staging laparoscopy confirmed peritoneal implants. Gastric cancer is the fifth most common malignancy worldwide and fourth leading cause of cancer-related deaths. RYGB is associated with a 4-fold reduction in the incidence of gastric cancer in animal models. Tinoco et al reported the incidence of gastric cancer in the excluded stomach to be 0.03% among 3047 patients who underwent bariatric surgery. However, larger prospective studies are lacking regarding the incidence of cancer in this population. Risk factors for gastric cancer include H. pylori infection, smoking, high-salt intake, family history of stomach cancer, obesity and a diet low in fruits and vegetables. Symptoms are non-specific and include anorexia, epigastric pain, anemia and weight loss following a period of stability or weight gain. Minimal invasive techniques which can be used to evaluate the excluded stomach are double balloon enteroscopy (DBE), percutaneous endoscopy, virtual gastroduodenoscopy, laparoscopic transgastric endoscopy and EUS. Patients with prior RYGB presenting with alarming, new onset, unexplained symptoms should prompt evaluation including adequate visualization of the excluded stomach with imaging and advanced endoscopic techniques.Figure: showing postoperative anatomy of modern RYGB.Figure: EUS showing antral wall thickening in the excluded stomach (arrow).Figure: Histology slide showing poorly differentiated adenocarcinoma.

Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight.

BACKGROUND/OBJECTIVESThis is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction.SUBJECTS/METHODSThe experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > 23 kg/m2) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < 1 × 10-4). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted.RESULTSWe found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; P = 8.0 × 10-7, rs1040675; 2.3 × 10-6) and BMI (rs10786764; P = 2.5 × 10-5, rs10786764; 6.57 × 10-5). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P <10 × 10-4. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < 1 × 10-4). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group.CONCLUSIONWe discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.

Family history, body mass index and survival in Japanese patients with stomach cancer: a prospective study.

Family history and nutritional status may affect the long-term prognosis of stomach cancer, but evidence is insufficient and inconsistent. To clarify the prognostic factors of stomach cancer, we conducted a prospective study of 1,033 Japanese patients with histologically confirmed stomach cancer who were admitted to a single hospital between 1997 and 2005. Family history of stomach cancer and pretreatment body mass index (BMI) were assessed using a self-administered questionnaire. Clinical data were retrieved from a hospital-based cancer registry. All patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to family history in parents and siblings and BMI category. During a median follow-up of 5.3 years, 403 all-cause and 279 stomach cancer deaths were documented. Although no association with family history was observed in the patients overall, analysis according to age group found an increased risk of all-cause death associated with a history in first degree relatives (HR = 1.61, 95% CI: 0.93-2.78, p = 0.09) and with a parental history (HR = 1.86, 95% CI: 1.06-3.26) among patients aged under 60 years at diagnosis. BMI was related to all-cause and stomach cancer death among patients aged 60 and over, showing a J-shaped pattern (HR of all-cause death = 2.28 for BMI < 18.5; HR = 1.61 for 25 ≤ vs. ≥ 23.0 to < 25.0 kg/m(2)). A family history of stomach cancer, especially parental history, may affect mortality among younger stomach cancer patients, whereas nutritional status may be a prognostic factor in older patients.

Gastric Cancer in Young Patients

Aim. The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. Patients and Methods. Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. Results. Male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. Conclusion. Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance.

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.

Association between insulin‐like growth factor‐1 polymorphisms and stomach cancer risk in a Japanese population

The insulin-like growth factor (IGF) signaling system plays a central role in cellular growth, differentiation and proliferation. Although the association between IGF1 gene polymorphisms and cancer risk has been evaluated for several carcinomas, this association has not yet been examined for stomach cancer. We investigated the association between IGF1 polymorphisms and the risk of stomach cancer in a Japanese population. A total of 703 patients with stomach cancer and 1462 non-cancer control subjects were enrolled in this case-control study. Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in multiple logistic regression models. We observed that the C allele in rs1520220 and the G allele in rs4764887 were significantly associated with stomach cancer risk in the per-allele model after adjusting for other risk factors (OR: 1.14 [95% CI: 1.00-1.30] and OR: 1.18 [95% CI: 1.02-1.36], respectively). We also observed a positive and dose-dependent association between the number of risk alleles and stomach cancer risk (P-trend: 0.019) when examining the two loci in the same model. These associations were still seen after adjusting for potential confounders, including sex, age, smoking status, history of diabetes and family history of stomach cancer. We did not find any significant interaction between these factors and the number of risk alleles. In conclusion, we observed a significant association between IGF1 polymorphisms and stomach cancer risk among a Japanese population. Examination of the biological significance of IGF1 is warranted.

“How do you live without a stomach?”: A multiple case study examination of total gastrectomy for palliation or prophylaxis

The number of diagnosed cases of stomach cancer in Western countries is relatively small compared to prevalence rates in Eastern populations. This disparity creates a general lack of information and understanding of the experience of patients treated for this disease in North America. Surgical removal of the stomach, also called total gastrectomy (TG), is presently the only curative treatment available to patients with stomach cancer. Considering the impact such a procedure may have, very little is known about what factors influence an individual's postsurgical quality of life (QL). This article reviews current literature and examines three unique case studies. Semi-structured interviews were analyzed using content analysis, a qualitative analytic approach for reporting combined subject responses. Participants included one 37-year-old man with multiple polyps in his stomach and a family history of stomach cancer, one 18 year-old man with a confirmed CDH1 mutation and a family history of stomach cancer, and one 33-year-old man with confirmed metastatic gastric adenocarcinoma. Subjective patient experience was categorized into: (1) making the decision, (2) treatment impact, and (3) life after TG. Prior to surgery, all patients carefully evaluated their perceived risk compared to the treatment consequences and indicated that a certain event triggered their decision. The largest treatment impacts were learning to eat again and adjusting to the physical changes. Each patient endorsed that their experience made them appreciate and make the most of life. This currently represents the only study to investigate the lived experience of TG for prophylaxis or palliation in individuals with and without genetic risk for stomach cancer. Understanding this process will allow all members of the cancer care team, and the patients themselves, to better understand the factors involved in decision making and postoperative adjustment. Fruitful avenues for future research are discussed.

Abstract 2202: Identification of CDH1 mutations in patients with lobular carcinoma with and without a family history of gastric cancer

Abstract Background: The E-cadherin (CDH1) gene is involved in cell adhesion and maintenance of tissue architecture. Loss of expression of CDH1 has been found in both invasive lobular carcinoma (ILCA) of the breast as well as hereditary diffuse gastric cancer (HDGC). While mutations in CDH1 have been found in patients with hereditary diffuse gastric cancer, less is known about the role of CDH1 mutations in patients with breast cancer, thus mutation status was determined in a breast cancer cohort with and without family histories of gastric cancer. Methods: The Clinical Breast Care Project database was queried to identify all patients with ILCA with or without a family history of gastric or stomach cancer as well as those with non-lobular invasive cancer with a family history of gastric or stomach cancer. Genomic DNA was isolated from peripheral blood samples. DNA variants were detected for each exon using high-resolution melting technology and the underlying change identified by direct sequencing. Results: Of the 72 patients with ILCA, five had a first degree relative with stomach cancer; 14 patients with non-lobular invasive cancer (12 IDCA, one mixed lobular and ductal, and one tubular) had first degree relatives with stomach or gastric cancer. Three mutations previously associated with gastric cancer were identified: A617T and V832M were identified in a patient with ILCA with no history of gastric cancer and in a patient with IDCA with a family history of gastric cancer, respectively, while one patient with ILCA and no family history harbored the splice site mutation 1137G-T. Three novel variants were also identified: G879S, in a patient with ILCA and no family history, P825Q in a patient with mixed lobular and ductal features with a family history of stomach cancer and L230F in a patient with IDCA and a family history of stomach cancer. Conclusions: The frequency of CDH1 mutations in this patient population was low (∼7%) and were split between patients with ILCA and no family history of gastric cancer and those with non-lobular cancers and at least one family member with gastric or stomach cancer. Identification of known mutations in patients with non-lobular carcinomas suggests that while these specific CDH1 mutations are associated with increased risk of hereditary diffuse gastric cancer, they do not confer increased risk for lobular cancer. In those patients with ILCA, the low frequency of germline mutations in CDH1 suggests alternate methods, such as epigenetic modification or miRNA silencing, may be driving the suppression of expression of E-cadherin and the development of ILCA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2202. doi:10.1158/1538-7445.AM2011-2202

Colonoscopy screening for individuals aged 40–49 years with a family history of stomach cancer in Korea

For asymptomatic individuals aged 40-49 years, screening for colorectal cancer is recommended only if individuals are at an increased risk. A family history of colon cancer (FHCRC) is considered to increase risk, however, whether family history of stomach cancer (FHSC) increases the risk of adenoma is not well known. We aimed to see whether FHSC increases the risk in asymptomatic individuals aged 40-49 years in Korea. Among asymptomatic individual aged 40-49 years who underwent colonoscopy screening, risk of adenoma was assessed according to FHCRC or FHSC. Of 3,160 individuals, male comprised 1,602 individuals (50.7%). FHCRC and FHSC was noticed in 163 (5.2%) and 227 (7.0%) individuals, respectively. Prevalence of adenoma was 31.9 %, 28.8%, and 22.3% for individuals with FHCRC, individuals with FHSC, and individuals without family history of cancer, respectively. FHSC was an independent risk factor for adenoma (odds ratio, 1.38; 95% confidence interval, 1.02-1.87, P = 0.039) in asymptomatic individuals aged 40-49 years. Compared with individuals with FHCRC, individuals with FHSC showed no difference in risk for adenoma (P = 0.347). As with individuals with FHCRC, individuals with FHSC might need to be considered as an individual with increased risk for adenoma. Therefore, earlier screening might be needed for asymptomatic individuals aged 40-49 years with FHSC in Korea.

Association of prostate stem cell antigen gene polymorphisms with the risk of stomach cancer in Japanese

A recent whole-genome association study identified a strong association between polymorphisms in the prostate stem cell antigen (PSCA) gene and stomach cancer risk. In this case-control study, we aimed to validate this association, and further to explore environmental factors possibly interacting with PSCA polymorphisms in 708 incident stomach cancer cases and 708 age-sex matched controls. The association between PSCA polymorphisms and Helicobacter pylori infection was also examined. We found that rs2294008 and rs2976392, which were strongly linked to each other (D' = 1.00), were significantly associated with stomach cancer risk. Per allele odds ratio for rs2994008 was 1.40 (95% confidence interval: 1.19-1.65; p = 3.7 x 10(-5)). We found significant interaction with a family history of stomach cancer in first-degree relatives (p-heterogeneity = 0.009). Similar to originally reported association, we found significant heterogeneity between diffuse and intestinal type (p-heterogeneity = 0.007). No association was seen between PSCA polymorphisms and H. pylori infection. In conclusion, PSCA polymorphisms are associated with stomach cancer risk in Japanese. A possible interaction with family history warrants further evaluation.

Family history of various cancers and pancreatic cancer mortality in a large cohort

A family history of pancreatic cancer is associated with increased risk of pancreatic cancer, but uncertainty remains about the magnitude of this association, whether it varies by age or smoking and whether a family history of other cancers may also be associated with increased risk. We examined family history of 14 cancers and pancreatic cancer mortality among ~1.1 million men and women in Cancer Prevention Study-II (CPS-II). CPS-II participants completed a questionnaire at enrollment in 1982. During follow-up through 2006, there were 7,306 pancreatic cancer deaths. A family history of pancreatic cancer in a parent or sibling was associated with pancreatic cancer mortality [multivariable adjusted rate ratio (RR) = 1.66, 95% confidence interval (CI) 1.43-1.94]. This association was stronger among participants aged under 60 (RR = 2.89, 95% CI 1.67-5.02) than among participants aged 60 or older (RR = 1.61, 95% CI 1.37-1.88). Weaker associations were observed for family history of stomach cancer (RR = 1.23, 95% CI 1.11-1.37), liver cancer (RR = 1.25, 95% CI 1.10-1.43), and colorectal cancer (RR = 1.12, 95% CI 1.01-1.23). Results from this large prospective study indicate family history of pancreatic cancer is associated with a moderate increase in risk of pancreatic cancer, and also identify associations with the family history of certain other cancers which may be useful in generating hypotheses about shared risk factors.

Family history of cancer and stomach cancer risk

A family history of stomach cancer in first-degree relatives increases the risk of stomach cancer, but uncertainties remain as concerns the variation of the risk according to age, sex and type of relative, as well as on the role of family history of other cancers. We investigated the issue using data from a multicentric case-control study conducted in Italy between 1997 and 2007 on 230 cases aged not more than 80 years, with histologically confirmed incident gastric cancer and 547 controls admitted to hospital for acute, non neoplastic conditions. Logistic regression models adjusted for the effect of sex, age, year of interview, education, body mass index (BMI), tobacco smoking and number of brothers and sisters were used to estimate the odds ratios (OR) of stomach cancer. Relative to subjects with no history, those with a family history of gastric cancer had an OR of 2.5 (95% confidence interval (CI) 1.5-4.2). No significant heterogeneity emerged according to sex or age of the proband or of the affected relative, or smoking habits, BMI and education of the proband. As suggested from previous studies the OR was higher when the affected relative was a sibling (OR=5.1, 95% CI: 1.3-20.6) rather than a parent (OR=2.2, 95% CI: 1.2-3.9), although the heterogeneity test was not significant. The risk of stomach cancer was not increased in subjects with a family history of cancer at any other site. The OR for all sites excluding stomach was 1.0 (95% CI: 0.7-1.4).

Features of Gastric Neoplasm Detected during the Screening Examination

Gastric cancer is the leading malignancy in Korea and early detection through the health screening seems to be important. The aims of this study were to investigate the features of gastric neoplasms detected during screening, and to figure out the risk factors of these lesions. From October 2003 to September 2005, subjects who visited Seoul National University Hospital Healthcare System Gangnam Center for health check-up were included in the study. The program included a questionnaire and tests including anti-Helicobacter pylori (H. pylori) antibody, esophagogastroduodenoscopy or double contrast upper gastrointestinal study. To figure out the risk factors, an age and gender-matched, four-fold sized control group was selected from the subjects. Of 25, 432 subjects, 122 cases of gastric neoplasms were detected including 61 adenocarcinoma (45 early gastric cancers), 53 adenoma, 7 mucosa-associated lymphoid tissue lymphoma, and one metastatic cancer. There was no significant statistical difference in basal characteristics of the subjects between gastric adenocarcinoma and adenoma. When comparing with the control group those without gastric neoplasms, smoking history, family history of stomach cancer, and H. pylori seropositivity were found to be significant risk factors for gastric neoplasms. Metabolic syndrome was more prevalent in adenoma than in the control (p<0.05). The health screening may be beneficial in early detection of gastric cancer. In addition, metabolic syndrome might be related with gastric adenoma.

OCCUPATIONAL EXPOSURE TO WHEAT PRODUCTS TRIGGERS CELIAC DISEASE EXACERBATION

Strict adherence to a gluten free diet is the recommended treatment for celiac disease. We report an unusual case where an occupational exposure to wheat flour reactivated gluten sensitive enteropathy. In 1999, a 56 year-old Caucasian male presented with iron deficiency anemia, fatigue, and weight loss. The patient reported a change in bowel habits from constipation to occasional loose stools 1–2 times a week, associated with fat intolerance. He was referred to a gastroenterologist for evaluation of anemia and possible malabsorption. His medical history is significant for Type II Diabetes Mellitus and a family history of stomach cancer. In addition, the patient takes Naprosyn for low back pain and arthralgias. Physical examination was significant for a weight of 152 pounds (ideal body weight of 172 lbs.) CBC revealed a Hematocrit of 27.6 with an MCV of 72. An initial colonoscopy was unremarkable. An EGD revealed nonerosive gastritis and a scalloped appearance of the duodenum. Duodenal biopsies confirmed celiac disease with moderate villous blunting and chronic inflammation. Anti-gliadin antibody IgA was positive. The patient was started on a gluten-free diet and his diarrhea and anemia improved. He managed to regain considerable weight and had 1–2 formed bowel movements a day. Repeat endoscopy five months later showed mild villous blunting without significant inflammation. A repeat Hematocrit was 41.5. In 2001, the patient began working at a bakery performing maintenance. Since starting work, he developed episodes of diarrhea once a week with explosive loose stools, fatigue, and malaise. His symptoms typically worsened towards the end of the workweek despite adherence to a strict gluten-free diet. He also developed vesicular-bullous lesions on his shoulders and buttocks. Upper endoscopy and duodenal biopsies were repeated and revealed moderate chronic inflammation and mild villous blunting. It was believed that the patient's occupational exposure to wheat flour (gluten) contributed to his worsening symptoms. The patient was advised to wear an N-95 particulate respiratory mask to decrease exposure to wheat while at work. He was also started on dapsone for Dermatitis Herpetiformis. After wearing the mask at work, the patient noted improvement of his diarrhea and skin lesions. A repeat EGD and biopsy showed considerable improvement in the villous atrophy and a decrease in the number of intraepithelial lymphocytes.