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Background. New serum pepsinogen (PG) criteria have been shown to indicate more accurately infection with Helicobacter pylori (H. pylori). We sought to improve risk classification for gastric cancer by adopting the new PG criteria with the addition of an H. pylori antibody test. Methods. The study participants were 275 patients with gastric cancer and 275 apparently healthy controls from case–control study data. We cross-sectionally compared the results of gastric cancer risk classifications that were based on a combination of the new PG criteria (PG II ≥ 10 ng/mL or PG I/II ≤ 5) and an H. pylori antibody test with those that were based on a combination of the conventional criteria (PG I ≤ 70 ng/mL and PG I/PG II ≤ 3) and an H. pylori antibody test. Results. Applying the conventional criteria resulted in 89 controls being classified as low risk. Applying the new criteria resulted in 23 controls (bootstrapped 95% confidence intervals [CI]: 14, 32) being additionally classified as high risk. Eight patients with gastric cancer were classified as low risk using the conventional criteria; however, six of these patients were classified as high risk by the new criteria (bootstrapped 95% CI: 2, 11). Conclusions. Compared with the conventional criteria, the new PG criteria with H. pylori antibody reduced instances of gastric cancer cases being misclassified as low risk. These findings suggest that the new PG criteria may help identify individuals at high risk of developing gastric cancer.

Background and Aim The causal relationship between Helicobacter pylori (H. pylori) infection and gastric cancer has been established. Although the magnitude of the carcinogenic effect of H. pylori is the next concern, it has not been sufficiently evaluated in Japan. Spontaneous disappearance of H. pylori infection may have provoked underestimation of the carcinogenic effect of the infection. To reduce the influence, a comparison should be carried out between subjects with and without the infection history. Cutoff values of H. pylori antibody lower than the manufacturer's recommendation are known to be more appropriate to diagnose history of H. pylori infection. The aim was to evaluate the carcinogenic effect of H. pylori. Methods A case–control study consisting of 275 gastric cancer patients and 275 age‐ and sex‐matched controls was performed. Serum H. pylori antibody was measured using the “JHM‐Cap” kit with a domestic antigen (cut value of the manufacturer's recommendation was 2.3 EV: ELISA value). Using a conditional logistic model, the odds ratios (ORs) for five cutoff values adjusted for smoking and drinking doses were calculated. Results For cutoff values of 1.25, 1.5, 1.75, 2.0, and 2.3 EV, the ORs (95% confidence intervals) were 67.7 (9.1, 502), 37.2 (8.8, 157), 21.3 (9.0, 60.2), 25.5 (9.0, 72.7), and 25.9 (9.2, 73.2), respectively. Conclusions These results suggest that the risk ratio of gastric cancer between subjects with and without history of H. pylori infection in Japan may exceed 20. Spontaneous disappearance of H. pylori infection may have provoked underestimation of the relative risk that reflects the carcinogenic effect of the infection. To reduce the effect of the spontaneous disappearance, comparison should be done between subjects with and without the infection history, and the relative risk is estimated to be more than 20 in Japan.

The relationship between gastric cancer and serum vascular endothelial growth factor receptor‐1 (sVEGFR‐1) and sVEGFR‐2, which are soluble form receptor proteins of vascular endothelial growth factor (VEGF), has not been extensively studied. VEGF, sVEGFR‐1 and sVEGFR‐2 were measured in the sera obtained before surgical operation from 164 gastric cancer patients and from 164 healthy controls matched for age and gender. Compared with controls, the cases showed elevated VEGF (P < 0.01) and reduced sVEGFR‐1 (P = 0.07) and sVEGFR‐2 (P = 0.02). The difference in VEGF levels was small among men and when the outcome was early cancer. The difference in sVEGFR‐1 levels was significant or borderline significant only in men and when the outcome was diffuse type cancer. The difference in sVEGFR‐2 levels was significant only in men and when the outcome was advanced or diffuse type cancer. The sensitivities and specificities of VEGF, sVEGFR‐1 and sVEGFR‐2 were all approximately 60%. For diffuse type cancer, sVEGFR‐2 showed a sensitivity of 62.4% and a specificity of 63.4%, which was similar to serum pepsinogen. In conclusion, elevated VEGF and reduced sVEGFR‐1 and sVEGFR‐2 in serum are characteristic of gastric cancer patients, and the value of serum sVEGFR‐2 in the diagnosis of diffuse type gastric cancer should be further evaluated. (Cancer Sci 2011; 102: 866–869)

Midkine (MK) is one of a family of heparin‐binding growth factors, and increased MK expression is reported in various types of human carcinomas. To clarify the association between serum MK (S‐MK) concentrations and gastric cancer, we examined S‐MK concentrations of gastric cancer patients (n = 275) and healthy controls (n = 275). S‐MK concentrations of all subjects were measured by enzyme‐linked immunosorbent assay (elisa). The medians (25th and 75th percentiles) of S‐MK were 192 (123 and 314) pg/mL in the cases and 170 (81 and 273) pg/mL in the controls (P < 0.01). We also compared S‐MK concentrations in each group divided by the progression stage or histological type of cancer. A difference was observed in the median S‐MK concentrations between early and advanced cancers [182 (105 and 301) pg/mL vs 203 (139 and 331) pg/mL, P = 0.07], but not between intestinal and diffuse type cancers [185 (121 and 306) pg/mL vs 198 (127 and 323) pg/mL, P = 0.51]. We found that those progression stages affect S‐MK concentration more strongly than the histological types in gastric cancer patients. Because S‐MK seems to reflect the progression stage of gastric cancer, it may serve as a useful marker in the clinical follow‐up of gastric cancer patients. (Cancer Sci 2005; 96: 54 –57)

We conducted a case‐control study to evaluate the association between serum levels of copper/zinc superoxide dismutase (Cu/Zn SOD) and the risk of gastric cancer. Cases were 214 patients who had been diagnosed with gastric cancer and controls were 120 persons who underwent medical checkups. Serum levels of Cu/Zn SOD were determined by enzyme‐linked immunosorbent assay (ELISA). Compared with the lowest quartile, the OR (odds ratio) was 4.54 (95% CI (confidence interval), 1.62–12.66) for the third quartile and 15.75 (95% CI, 5.84–42.46) for the highest quartile. With both early and advanced cancers, as well as with the intestinal and diffuse types, a significant increase in risk was observed with increasing levels of serum Cu/Zn SOD. Our case‐control study showed that serum levels of Cu/Zn SOD were significantly elevated in gastric cancer patients compared with apparently healthy controls, and higher Cu/Zn SOD levels may be associated with an increased risk of gastric cancer.

Few risk factors for gallbladder cancer have been identified with sufficient statistical power, because this cancer is rare. The present study was conducted to evaluate the association of bowel movement frequency and medical history with the risk of death from gallbladder cancer using the data set from a large‐scale cohort study. A total of 113,394 participants (42.0% males), aged 40 to 89 years, were followed up for 11 years. Information on the medical history of selected diseases, history of blood transfusions, frequency of stools, and tendency toward diarrhea at baseline was collected through a self‐administered questionnaire. The Cox proportional hazard model was used to estimate the hazard ratio (HR). During the follow‐up period, a total of 116 deaths (46 males, 70 females) from gallbladder cancer were identified. After adjustments for age and gender, history of hepatic disease (HR: 2.28; 95% confidence intervals (95% CI): 1.24–4.21), frequency of stool, and tendency toward diarrhea (HR: 0.26; 95% CI: 0.08‐0.83) were found to be significantly associated with the risk of death from gallbladder cancer. Compared with those who had a stool at least once a day, the HR was 2.06 (95% Cl: 0.82–5.18) for those who had a stool less than once in 6 days (P for trend=0.050). In this prospective study, constipation and a history of hepatic disease were found to elevate the risk of gallbladder cancer death, whereas a tendency toward diarrhea diminished it.

PurposeMetastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a prognostic marker for the metastasis of early-stage non-small cell lung cancer (NSCLCs). We studied MALAT1 expression in breast cancer in relation to disease features and patient survival.MethodsQuantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure MALAT1 expression in tumor samples of 509 breast cancer patients. Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between MALAT1 expression and breast cancer survival using the Cox proportional hazards regression model, and the analysis was adjusted for age at surgery, tumor grade, disease stage, and hormone receptor status. Meta-analysis of multiple microarray datasets from online databases and our own study was performed to evaluate the association of MALAT1 with breast cancer survival.ResultsPatients with low-grade or ER-positive tumors had higher expression of MALAT1 compared to those with high-grade (p = 0.013) or ER-negative (p = 0.0002) tumors. Patients with PR-positive tumors also had higher MALAT1 expression than those with PR-negative tumors (p < 0.0001). In patients with positive hormone receptors or low tumor grade, tumors with high MALAT1 expression were more likely to recur. Survival analysis showed that patients with high expression of MALAT1 had a twofold increase in risk of relapse (p = 0.0083) compared to those with low expression. This association remained significant after adjustment for age at surgery, disease stage, tumor grade, and hormone receptor status. Meta-analysis showed that high MALAT1 expression was associated with poor relapse-free survival in patients with hormone receptor-positive tumors (HR 1.44, 95% CI 1.08–1.92).ConclusionsHigh expression of lncRNA MALAT1 is associated with breast cancer relapse and may play a role in tumor progression.

The etiology of pancreatic cancer remains largely unknown. We examined the association of pancreatic cancer deaths with menstrual and reproductive factors in a cohort study involving Japanese women. A total of 63,273 women were followed up for mortality from 1988 to 1999. Information on menstrual and reproductive factors was obtained by a questionnaire survey at baseline. Cox proportional-hazards models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for death from pancreatic cancer in relation to menstrual and reproductive factors. During 631,401 person-years of follow-up, 154 women died from pancreatic cancer. Parity was not significantly associated with the risk of death from pancreatic cancer; the RR was 0.80 (95% CI, 0.31-2.11) for women with six or more births compared with women with zero or one birth. We found no significant overall association with other reproductive factors, including pregnancy, age at first birth, and menopause. The risk appeared to increase with increasing age at menarche; the RR was 1.49 (95% CI, 0.95-2.34) for women who had menarche after 16 years of age compared to those who had menarche before they were 15 years old. Our prospective data indicate that menstrual and reproductive factors are not associated with the risk of death from pancreatic cancer among Japanese women.

Objective To examine the relationship of baseline levels of serum TGF-β1 to the subsequent risk of death from pancreatic cancer in a nested case-control study. Methods The cases were 85 persons who had provided a blood sample at baseline and subsequently died of pancreatic cancer during the study period. For each case, three controls were randomly selected from among the cohort participants, and were matched for each case by sex, age (±1 year), and study area. Serum TGF-β1 levels were measured with enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from conditional logistic models. Results The mean of serum TGF-β1 levels was significantly higher among cases than among controls (p = 0.01). Individuals with serum TGF-β1 levels in the highest quartile had a 2.5-fold increase in risk as compared with those in the lowest quartile (OR, 2.5; 95% CI, 0.9-6.9), after adjustment for month of blood draw, cigarette smoking, body mass index and history of diabetes. Excluding 12 pancreatic cancer deaths that occurred within three years of follow-up did not alter the positive association. Conclusion Our prospective data indicate that high serum TGF-β1 levels may be associated with an increased risk of death from pancreatic cancer.

Although age-adjusted mortality from gastric cancer has been decreasing in Japan, the crude incidence of gastric cancer shows a slight increase. We have observed trends in the incidence of gastric cancer by sex and 20-year age groups over the past two decades (1976-1996). Source data were obtained from the cancer statistics materials provided by the Research Group for Population-Based Cancer Registration in Japan. Simultaneously, we observed changes in the prevalence of Helicobacter pylori infection and in serological atrophy of the gastric mucosa, and compared the results with those involving changes in the incidence of gastric cancer. A slight decline was observed in all age groups over 40 years old, in both men and women, between 1986 and 1996. However, a marked decline in incidence was observed for those aged 20-39 years. The prevalence of H. pylori infection declined in both sexes between 1989 and 1998. The frequency of serological atrophy of the gastric mucosa significantly declined in all age groups between 1989 and 1996, with young age groups experiencing a more marked decrease. The marked decline in gastric cancer incidence observed in the young population will also begin to occur in the elderly population in the future.