Gastric Cancer In First-degree Relatives Research Articles

Risk of Gastric Cancer is Highly Dependent on Type of First-Degree Family Member Affected by Cancer: Lessons from a High-Risk Population in Iran.

Family history of gastric cancer (GC) in first-degree relatives may increase the risk of GC. This study aimed to assess how family history of GC in first-degree relatives really affects the risk of GC in an extremely high-risk population. A large population-based case-control study was carried out on 1222 incident GC cases and 1235 controls in Ardabil Province-a high-risk area in North-West Iran-to assess the associations of GC family history in first-degree relatives with the risk of GC (2003-2017). GC family history did not significantly associate with the risk of GC overall (ORadj=1.09, 95% CI: 0.80-1.47, P=0.589). It found no significant association of GC family history in a parent, and in a father, mother, and sister separately, with the risk of GC. However, GC risk was significantly associated with a history of GC in a sibling (ORadj=1.61, 95% CI: 1.11-2.35, P=0.013), especially brother (ORadj=2.24, 95% CI: 1.41-3.64, P=0.0008). The risk was greatly increased in subjects with two or more affected brothers (ORadj =5.56, 95% CI: 2.33-14.20, P=0.0002). We did not find a familial tendency to cardia GC and non-cardia GC as well as histopathologic features. Determining the type of first-degree relationships with GC may, therefore, be more important than assessing family history alone for predicting the risk of GC in this high-risk area.

Identifying the Profile of Helicobacter pylori-Negative Gastric Cancers: A Case-Only Analysis within the Stomach Cancer Pooling (StoP) Project.

The prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serologic test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (OR). Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n = 166/853) and decreased to 7.0% (n = 55) when considering CagA status; estimates for all criteria were 21.8% (n = 276/1,325) and 6.6% (n = 97), respectively. HpNGC had a family history of gastric cancer more often [OR = 2.18; 95% confidence interval (CI), 1.03-4.61] and were current smokers (OR = 2.16; 95% CI, 0.52-9.02). This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.

Association between gastric cancer and the family history of gastric cancer: a cross-sectional study using Korean Genome and Epidemiology Study data.

The risk of gastric cancer based on a family history of gastric cancer remains unclear. The purpose of this study was to investigate the relationship between gastric cancer and family history of gastric cancer within a large cohort in Korea. In total 211 708 participants were recruited in the Korean Genome and Epidemiology Study during 2001-2013, and divided into a group with a self-reported personal history of gastric cancer ( n = 930) and a 1:40 matched control group ( n = 37 200). We examined the family history of gastric cancer in first-degree relatives for cross-sectional analysis. Logistic regression was used to estimate the odds ratios (ORs) of gastric cancer according to family history, using four models that were adjusted for different confounding variables, including the interaction among a family history of gastric cancer. After matching the two groups for age and sex, the gastric cancer group had a significantly higher proportion of family history in each relative than the controls ( P < 0.001). In the adjusted model, the ORs [95% confidence interval (CI)] for gastric cancer with a history of an affected father, mother and sibling were 1.80 (1.38-2.34), 1.95 (1.42-2.69) and 2.98 (2.31-3.83), respectively, compared with those in the control group. There was no statistically significant interaction among a family history of gastric cancer in each relative. A history of gastric cancer in siblings, among first-degree relatives, is strongly associated with an increased risk of gastric cancer. Regular follow-up and early treatment are recommended for those with a family history of gastric cancer.

Preferences of first-degree relatives of gastric cancer patients for gastric cancer screening: a discrete choice experiment

BackgroundIt is very necessary to implement gastric cancer screening in China to reduce the mortality of gastric cancer, but there are no national screening guidelines and programs. Understanding of individual preferences is conducive to formulating more acceptable screening strategies, and discrete choice experiments can quantify individual preferences. In addition, the first-degree relatives of gastric cancer patients are at high risk for gastric cancer. Compared with those without a family history of gastric cancer, the risk of gastric cancer in first-degree relatives of gastric cancer patients is increased by 60%. Therefore, a discrete choice experiment was carried out to quantitatively analyse the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening to serve as a reference for the development of gastric cancer screening strategies.MethodsA questionnaire was designed based on a discrete choice experiment, and 342 first-degree relatives of gastric cancer patients were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model.ResultsThe five attributes included in our study had a significant influence on the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening (P < 0.05). Participants most preferred the sensitivity of the screening program to be 95% (coefficient = 1.424, P < 0.01) with a willingness to pay 2501.902 Yuan (95% CI, 738.074–4265.729). In addition, the participants’ sex and screening experiences affected their preferences. An increase in sensitivity 35 to 95% had the greatest impact on the participants’ willingness to choose a gastric cancer screening program.ConclusionThe formulation of gastric cancer screening strategies should be rooted in people’s preferences. The influence of sex differences and screening experiences on the preferences of people undergoing screening should be considered, and screening strategies should be formulated according to local conditions to help them play a greater role.

Risk factors for gastric cancer: a large-scale, population-based case-control study.

Background:Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC.Methods:Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI).Results:A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219–0.599, P < 0.001), overweight/obesity (BMI ≥24 kg/m2; OR = 0.489, 95% CI = 0.329–0.726, P < 0.001), cigarette smoking (OR = 3.069, 95% CI = 1.700–5.540, P < 0.001), alcohol consumption (OR = 1.661, 95% CI = 1.028–2.683, P = 0.038), history of stomach disease (OR = 6.917, 95% CI = 4.594–10.416, P < 0.001), and family history of GC in first-degree relatives (OR = 4.291, 95% CI = 1.661–11.084, P = 0.003) were significantly correlated with the occurrence of GC. Subgroup analyses by age and gender indicated that GC risk was still increased in the presence of a history of stomach disease. A history of chronic gastritis, gastric ulcer, or gastric polyposis was positively associated with GC, with adjusted ORs of 4.155 (95% CI = 2.711–6.368), 1.839 (95% CI = 1.028–3.288), and 2.752 (95% CI = 1.197–6.326).Conclusions:Subjects who smoke, drink, with history of stomach disease and family history of GC in first-degree relatives are the high-risk populations for GC. Therefore, attention should be paid to these subjects for GC screening.

Paradigm-Shifting Research in Gastroenterology, Hepatology, and Nutrition: A Top 20 List of Articles Published in 2020

Paradigm-Shifting Research in Gastroenterology, Hepatology, and Nutrition: A Top 20 List of Articles Published in 2020

Cost‑effectiveness Analysis of Helicobacter pylori Eradication Therapy in First-Degree Relatives of Patients with Gastric Cancer.

BackgroundHelicobacter pylori (H. pylori) eradication therapy has been shown to reduce the risk of gastric cancer in patients who have a family history of gastric cancer in first-degree relatives. The aim of this study was to assess the cost-effectiveness of H. pylori eradication therapy in a select population in the People's Republic of China.MethodsA Markov model was applied to evaluate the cost-effectiveness of H. pylori eradication therapy. The long-term costs of H. pylori eradication therapy were calculated from the Chinese perspective. Health outcomes were measured by quality-adjusted life years (QALYs). Epidemiological information and health utilities used in the model were collected from published literatures or statistical bureaus. A sensitivity analysis was conducted to explore the influence of parameters on the uncertainty of the model.ResultsCompared with the no eradication therapy group, H. pylori eradication therapy prolonged an average of 4.52 QALYs (32.64 QALYs vs 28.12 QALYs) and saved $3227.07 ($2472.83 vs $5699.90). The cost-effectiveness analysis demonstrated that no H. pylori eradication therapy cost more and produced less QALYs. It was dominated by H. pylori eradication therapy. The one-way sensitive analyses proved that the results were robust to the fluctuations of the input parameters.ConclusionH. pylori eradication therapy not only reduced the risk of gastric cancer in first-degree relatives of patients with gastric cancer but also was an economical strategy with lower costs and greater efficacy.

Helicobacter pylori Eradication Therapy to Prevent Gastric Cancer in First-degree Relatives of Gastric Cancer Patient

<i>Helicobacter pylori</i> Eradication Therapy to Prevent Gastric Cancer in First-degree Relatives of Gastric Cancer Patient

Noneffectiveness of scopolamine for facilitating detection of upper gastrointestinal neoplasia during screening esophagogastroduodenoscopy: propensity score-matched study.

Antispasmodics, such as scopolamine, are widely used in several countries prior to diagnostic and screening esophagogastroduodenoscopy (EGD), with the goal of optimizing the detection of minute lesions, typically early gastric cancer (T1 lesions). The aim of this study was to determine whether scopolamine facilitates detection of gastric cancer in the screening setting. A propensity score-matched retrospective study was conducted in a tertiary referral medical center in Tokyo, Japan. Consecutive individuals (n = 40 776) underwent screening EGD between January 2011 and May 2016. All outcome lesions were diagnosed with histopathological confirmation. Detection of esophageal cancer, gastric adenoma, duodenal adenoma, and upper gastrointestinal neoplasia (UGIN) were investigated as secondary outcomes. Scopolamine was used in 31 130 patients (76.3 %) and propensity score matching yielded 6625 pairs. Bivariate analysis revealed no significant association between possible confounders (age, sex, overweight, atrophic gastritis, alcohol history, smoking history, midazolam use, endoscopist biopsy rate grade, and gastric cancer in first-degree relatives) and scopolamine use. Lesions detected were 18 gastric cancers, 11 esophageal cancers, 19 gastric adenomas, 6 duodenal adenomas, and 54 UGINs, with no significant association between scopolamine use and lesion detection. Scopolamine use did not appear to effectively facilitate detection of gastric or esophageal cancer, gastric or duodenal adenoma, and UGIN during screening EGD. Scopolamine should be avoided until its efficacy is confirmed by a randomized controlled trial.

Family History of Gastric Cancer and Helicobacter pylori Treatment

BackgroundHelicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown.MethodsIn this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period.ResultsA total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P=0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).ConclusionsAmong persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.)

Community-Based Pilot Study of a Screening Program for Gastric Cancer in a Chinese Population.

A majority of gastric cancer cases in China are diagnosed at advanced stages, chiefly due to lack of an established routine nationwide screening program. This study evaluated the effectiveness of a novel screening program for gastric cancer. Seven geographic communities were randomly selected, and residents ages 40-69 years were screened. Serologic tests of Helicobacter pylori antibodies and pepsinogens, and positive family history of gastric cancer in first-degree relatives (FDR), were used to differentiate individuals for further gastroscopic examination and gastric mucosal biopsies. Among 7,773 individuals who underwent examination of serum markers, gastric cancer was detected in 14 (1.8%; 10 men). The rate in terms of gastric cancer cases per 100 gastroendoscopies was 1.6% (14/872), which was greater than 0.87% previously reported. Eleven of 14 patients with gastric cancer (78.6%) were FDRs of patients with gastric cancer. Two-thirds of the subjects with cardia gastric cancer were FDRs of individuals with gastric cancer rather than cardia gastric cancer. Comparative analysis indicated that the gastric cancer subjects were significantly more likely to be FDRs of patients with gastric cancer, in contrast to those without gastric cancer. All the individuals with gastric cancer were aged ≥50 years. After conducting a reverse analysis, we propose a novel screening program for gastric cancer. In conclusions, the populations most vulnerable to gastric cancer are those with positive family history of gastric cancer in FDRs, male gender, and aged 50 years or older. This screening program using fewer serum markers combined individual risk factors, mainly FDRs, is novel for identification of high-risk individuals for further gastroscopy in detecting early gastric cancer.

Importance of tumor location and histology in familial risk of upper gastrointestinal cancers: a nationwide cohort study.

BackgroundFamilial clustering of upper gastrointestinal (UGI) cancers and the significance of family history has been addressed previously. We aimed to elucidate the familial risk based on the specified tumor location and histology.MethodIn the Swedish Family-Cancer Database, we determined the familial risk of UGI cancer patients diagnosed (1958–2015) with esophageal and gastric cancer by tumor location using standardized incidence ratios (SIRs).ResultsRisk of esophageal cancer in first-degree relatives (FDRs) of patients with esophageal cancer increased 2.4-fold (SIR 95% CI 2.0–2.8), whereas risk of esophageal cancer in cases with family history of cancer in the middle third of the esophagus increased 3.4-fold (SIR 95% CI 2.1–5.1). Risk of gastric cancer in FDRs increased 1.6-fold (SIR 95% CI 1.5–1.7), occurrence of concordant subsite gastric cancer in the antrum, body, and cardia was 5.5-fold (SIR 95% CI 2.4–11), 4.6-fold (SIR 95% CI 2.6–7.4), and 1.7-fold (SIR 95% CI 1.1–2.5), respectively. Familial risk of concordant histological subtype in esophageal cancer was 4.1-fold for squamous cell carcinoma (SIR 95% CI 3.2–5.2) and 3.6-fold for adenocarcinoma (SIR 95% CI 2.5–5.1). The risk of concordant gastric adenocarcinoma was 1.6-fold for one affected FDR (SIR 95% CI 1.5–1.7), 6.1-fold for two FDRs (SIR 95% CI 4.4–8.4), and 8.6-fold among twins (SIR 95% CI 2.3–22).ConclusionFamily history of cancer in the lower third of the esophagus and stomach cancer in specific locations such as the antrum, body, and cardia can be considered as important predictive evidence for cancer in the same location in relatives. Our findings might guide endoscopy-based surveillance by introducing subgroups of populations with a higher risk for UGI cancer with particular attention to concordance of location of lesions, which could be a reasonable strategy for early detection, and thus help save more lives.

What is the quantitative risk of gastric cancer in the first-degree relatives of patients? A meta-analysis.

AIMTo quantify the risk of gastric cancer in first-degree relatives of patients with the cancer.METHODSA comprehensive literature search was performed. Case-control trials comparing the frequency of a positive family history of gastric cancer in patients with gastric cancer, vs non-gastric cancer controls were retrieved. Studies with missed or non-extractable data, studies in children, abstracts, and duplicate publications were excluded. A meta-analysis of pooled odd ratios was performed using Review Manager 5.0.25. We performed subgroup analysis on Asian studies and a sensitivity analysis based on the quality of the studies, type of the outcome, sample size, and whether studies considered only first-degree relatives.RESULTSThirty-two relevant studies out of 612 potential abstracts (n = 80690 individuals) were included. 19.0% of the patients and 10.9% of the controls had at least one relative with gastric cancer (P < 0.00001). The pooled relative risk for the development of gastric cancer in association with a positive family history was 2.35 (95%CI: 1.96-2.81). The Cochran Q test for heterogeneity was positive (P < 0.00001, I² = 92%). After excluding the three outlier studies with the highest relative risks, heterogeneity remained significant (P < 0.00001, I² = 90%). The result was not different among Asian studies as compared to others and remained robust in several sensitivity analyses. In the 26 studies which exclusively analysed the history of gastric cancer in first-degree relatives, the relative risk was 2.71 (95%CI: 2.08-3.53; P < 0.00001).CONCLUSIONIndividuals with a first-degree relative affected with gastric cancer have a risk of about 2.5-fold for the development of gastric cancer. This could be due to genetic or environmental factors. Screening and preventive strategies should be developed for this high-risk population.

Gastric cancer and family history.

Gastric cancer is associated with high morbidity and mortality rates worldwide. Identifying individuals at high risk is important for surveillance and prevention of gastric cancer. Having first-degree relatives diagnosed with gastric cancer is a strong and consistent risk factor for gastric cancer, but the pathogenic mechanisms behind this familial aggregation are unclear. Against this background, we reviewed the risk factors for gastric cancer in those with a first-degree relative with gastric cancer, and the possible causes for familial clustering of gastric cancer including bacterial factors, inherited genetic susceptibility, environmental factors or a combination thereof. Among individuals with a family history, current or past Helicobacter pylori infection, having two or more first-degree affected relatives or female gender was associated with an increased risk of developing gastric cancer. To date, no specific single nucleotide polymorphism has been shown to be associated with familial clustering of gastric cancer. H. pylori eradication is the most important strategy for preventing gastric cancer in first-degree relatives of gastric cancer patients, particularly those in their 20s and 30s. Early H. pylori eradication could prevent the progression to intestinal metaplasia and reduce the synergistic effect on gastric carcinogenesis in individuals with both H. pylori infection and a family history. Endoscopic surveillance is also expected to benefit individuals with a family history. Further large-scale, prospective studies are warranted to evaluate the cost-effectiveness and optimal time point for endoscopy in this population. Moreover, genome-wide association studies that incorporate environmental and dietary factors on a ‘big data’ basis will increase our understanding of the pathogenesis of gastric cancer.

TNF-α-308/-238 polymorphisms are associated with gastric cancer: A case-control family study in China

Associations of TNF-α-308 (rs1800629) and -238 (rs361525) with gastric cancer had the inconsistent indication among different populations. In this case-control family study, 47families were determined with the probands diagnosed with gastric cancer (case family, n=296), accordingly 47families without gastric cancer were matched with the case families by multivariate distribution of age, sex, social class, and pedigree size (control family, n=319). Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) was used to identify the TNF genotype. Chi-square test was used to compare the groups regarding genotype and the allele frequencies, HWE test for Hardy-Weinberg equilibrium. The frequencies of TNF-α-308 GA and AA genotypes were significantly higher in case family than that in control family. The risk of gastric cancer was increased in GA and AA carriers in the first degree (OR=2.06, 95% CI=1.20-3.51 and OR=4.89, 95% CI=2.74-8.74), however the similar result was not found in the second degree. Helicobacter pylori infection status were significantly associated with risk of gastric cancer in first-degree relatives (OR=1.96, 95% CI=1.26-3.05) while no statistical significance was noted in the second-degree relatives. Haplotypes of TNF-α-308/-238 alleles, GA/GG, AA/GG and AA/GA indicated the susceptibilities to gastric cancer with OR and 95% confident intervals resulting 2.07 (1.34-3.21), 4.49 (2.74-7.33) and 4.98 (1.76-14.01) respectively. TNF-α-G308A (rs1800629) polymorphisms are associated with gastric cancer in Chinese population. Haplotypes of TNF-α-308/-238 GA/GG, AA/GG and AA/GA increase the susceptibilities to gastric cancer. The first-degree relatives are more likely to develop into gastric cancer with TNF-α-G308 polymorphisms and H.pylori positive than the second-degree are.

Clinical Factors Related with Helicobacter Pylori Infection - Is there an Association with Gastric Cancer History in First-Degree Family Members?

The aim of this study was to assess clinical factors associated with Helicobacter pylori positivity and to evaluate the incidence of gastric carcinoma in first-degree family members of infected patients. A total of 580 patients (mean age:38±17) with gastrointestinal complaints underwent C-14 urea breath test (UBT). Patients were grouped as: Group-1, untreated patients (n:384); and Group-2, patients who previously treated with eradication triple therapy (n:196). C-14 UBT was performed 1-2 months after the completion of eradication therapy. Associations of H pylori positivity with age, gender, ABO and Rhesus groups, smoking, dietary habits, and history of gastric cancer in first-degree family members were evaluated. The frequency of H pylori positivity was significantly higher in group-1 (58%) compared to group-2 (20%), p=0.001. There were no correlations between H pylori positivity and age, gender, ABO groups, Rhesus subgroups, smoking and dietary habits in both patient groups. The frequency of gastric cancer in family members was significantly higher in patients with H pylori infection among group-1, compared to infected patients among group-2 (56% vs. 28.6% respectively, p=0.03). We observed a significant association between H pylori positivity and the presence of gastric cancer in first-degree relatives of group-1 patients. Our results provide some confirmation of the presence of a link between gastric cancer development and H pylori. C-14 UBT is a sensitive, reliable and a widely recommended test for the detection of H pylori infection and recurrence. We suggest that detection and eradication of H pylori may contribute to a reduced risk of gastric cancer in the family members of infected patients.

Evaluation of apoptosis along with BCL-2 and Ki-67 expression in patients with intestinal metaplasia

The primary aim is to compare individuals with intestinal metaplasia (IM), chronic active gastritis (CAG), and normal gastric mucosa (NGM) in terms of apoptosis, proliferation, and Bcl-2 expression. The secondary aim is to determine whether these parameters are different between patients with and without gastric cancer in first-degree relatives. We enrolled 106 patients whose histopathological results were consistent with IM (n: 42), CAG (n: 51), or NGM (n: 13). Antral biopsies were immunohistochemically stained for Bcl-2 and Ki-67 expression. Apoptosis was detected using TUNEL assay. While no significant difference was determined between three groups with regard to apoptosis and Bcl-2 expression (p>0.05), Ki-67 expression was significantly higher in the IM group when compared with the CAG and NGM groups (29.90±22.87 vs. 18.18±16.22 vs. 18.54±20, respectively; p=0.012). Helicobacter pylori was determined to increase apoptosis (49.3% vs. 25.7%, p<0.05), nevertheless, it had no significant effect on proliferation and Bcl-2 expression. Bcl-2 and Ki-67 expression and apoptosis were not different among patients with and without a history of gastric cancer in first degree relatives. Although intestinal metaplasia cases demonstrate an increase in proliferation, no elevation is observed in apoptosis. This can be an important factor in the progression to gastric cancer.

Stomach Cancer Risk in Gastric Cancer Relatives

To identify the risk of gastric cancer in first-degree relatives of gastric cancer patients, and to determine if there is an interaction between Helicobacter pylori (H. pylori) infection and family history of gastric cancer in gastric carcinogenesis. It is unclear to what degree a family history of gastric cancer is associated with stomach cancer risk in Korea. From May 2003 to July 2008, 428 gastric cancer patients and 368 controls were included in the analyses. Logistic regression models including age, sex, family history of gastric cancer, residency during childhood, smoking, monthly income, spicy food diet and H. pylori status were evaluated to estimate the odds ratios (ORs) of developing gastric cancer. Adjusted OR for gastric cancer increased 3-fold for subjects reporting first-degree relatives with gastric cancer [OR 2.85, 95% confidence interval (CI): 1.83-4.46]. The association was strong in the 40 to 59 years age group (OR 4.00, 95% CI: 2.06-7.76), and became weaker in subjects older than 60 years of age (OR 1.81, 95% CI: 0.95-3.46). Compared with the uninfected subjects without a family history, subjects with both a family history and H. pylori infection had a 5-fold increased risk (OR 5.32, 95% CI: 2.76-10.25). After adjusting for environmental factors and H. pylori infection, a family history of gastric cancer remained independently associated with gastric cancer. The interaction between H. pylori infection and family history of gastric cancer might be a rationale for H. pylori eradication in the gastric cancer relatives as a strategy to prevent gastric cancer.

MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer

Two common mutations, 677 C→T and a1298 A→C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors. Helicobacter pylori (HP) infection was also determined. An increased risk was found for 677TT in GC patients with respect to blood donors (odds ratio (OR) = 1.98), and statistical significance was sustained when we compared sex–age-matched GC patients and donors (OR = 2.37). The 677TT genotype association with GC was found in women (OR = 3.10), while a reduction in the 667C allele frequency was present in both the sex. No statistically significant association was detected when 677–1298 genotype was stratified by sex and age. Men of GC-relatives showed a higher 1298C allele frequency than donors (OR = 4.38). Between GC and GC-relatives, HP infection frequency was similar. In conclusion, overall findings support the hypothesis that folate plays a role in GC risk. GC-relatives evidence a similar 677TT frequency to that found in the general population.

Familial clustering in subgroups of gastric cancer stratified by histology, age group and location

Aim To assess the risk of gastric cancer in a Japanese patient population with the disease by stratification with histology, age, tumour location and the association with family history of gastric or non-gastric tumours. Methods A retrospective analysis of 1400 consecutive patients with gastric cancer and 13,467 age- and gender-matched controls from a pre-recorded database using conditional logistic regression models. Results Young patients (≤43 years of age) with gastric cancer of intestinal type had a strong association with family history of gastric cancer in first degree-relatives (OR = 12.5). Moreover, when a history of gastric cancer was observed in both parents, there was an increased risk of gastric cancer intestinal type (OR = 7.8), more commonly in the proximal and mid-stomach. In contrast, there was an increased risk of diffuse-type cancer when both parents suffered non-gastric cancers (OR = 2.1). Conclusion These data suggest that the degree of familial clustering differ in gastric cancer subgroups stratified by histology, age, and stomach location in this Japanese population.