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Validation of a Blood Biomarker for Identification of Individuals at High Risk for Gastric Cancer
Epplein, Meira,Butt, Julia,Zhang, Yang,Hendrix, Laura H.,Abnet, Christian C.,Murphy, Gwen,Zheng, Wei,Shu, Xiao-Ou,Tsugane, Shoichiro,Qiao, You-lin,Taylor, Philip R.,Shimazu, Taichi,Yoo, Keun-Young,Par American Association for Cancer Research 2018 Cancer Epidemiology, Biomarkers & Prevention Vol.27 No.12
<P><B>Background:</B></P><P><I>Helicobacter pylori</I> is the leading cause of gastric cancer, yet the majority of infected individuals will not develop neoplasia. Previously, we developed and replicated serologic <I>H. pylori</I> biomarkers for gastric cancer risk among prospective cohorts in East Asia and now seek to validate the performance of these biomarkers in identifying individuals with premalignant lesions.</P><P><B>Methods:</B></P><P>This cross-sectional study included 1,402 individuals from Linqu County screened by upper endoscopy. <I>H. pylori</I> protein-specific antibody levels were assessed using multiplex serology. Multivariable-adjusted logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for prevalent intestinal metaplasia, indefinite dysplasia, or dysplasia, compared with superficial or mild atrophic gastritis.</P><P><B>Results:</B></P><P>Compared with individuals seronegative to Omp and HP0305, individuals seropositive to both were seven times more likely to have precancerous lesions (OR, 7.43; 95% CI, 5.59–9.88). A classification model for precancerous lesions that includes age, smoking, and seropositivity to <I>H. pylori</I>, Omp, and HP0305 resulted in an area under the curve (AUC) of 0.751 (95% CI, 0.725–0.777), which is significantly better than the same model, including the established gastric cancer risk factor CagA (AUC, 0.718; 95% CI, 0.691–0.746, <I>P</I><SUB>difference</SUB> = 0.0002).</P><P><B>Conclusions:</B></P><P>The present study of prevalent precancerous gastric lesions provides support for two new serum biomarkers of gastric cancer risk, Omp and HP 0305.</P><P><B>Impact:</B></P><P>Our results support further research into the serological biomarkers Omp and HP0305 as possible improvements over the established virulence marker CagA for identifying individuals with precancerous lesions in East Asia.</P>
Butt, Julia,Varga, Matthew G.,Wang, Tianyi,Tsugane, Shoichiro,Shimazu, Taichi,Zheng, Wei,Abnet, Christian C.,Yoo, Keun-Young,Park, Sue K.,Kim, Jeongseon,Jee, Sun Ha,Qiao, You-lin,Shu, Xiao-Ou,Waterboe AMERICAN ASSOCIATION FOR CANCER RESEARCH INC 2019 CANCER PREVENTION RESEARCH Vol.12 No.10
<P>Smoking is an established risk factor for gastric cancer development. In this study, we aimed to assess prospectively the association of smoking with gastric cancer risk in 1,446 non-cardia gastric cancer cases and 1,796 controls from China, Japan, and Korea with consideration of <I>Helicobacter pylori</I> infection as a potential effect modifier. Applying logistic regression models stratified by study and adjusted for age and sex we found that current, but not former, smoking was significantly associated with gastric cancer risk [OR = 1.33; 95% confidence interval (CI), 1.07–1.65]. However, the association was significant only in <I>H. pylori</I> sero-positive individuals determined by 3 different sero-markers: overall sero-positivity, sero-positivity to the onco-protein CagA, and sero-positivity to the gastric cancer associated sero-marker HP0305 and HP1564. Specifically, a significant interaction was found when stratifying by HP0305/HP1564 (<I>P</I><SUB>interaction</SUB> = 0.01) with a 46% increased risk of gastric cancer among HP0305/HP1564 sero-positive current smokers (95% CI, 1.10–1.93) as opposed to no increased gastric cancer risk among HP0305/HP1564 sero-negative current smokers (OR = 0.93; 95% CI, 0.65–1.33). We confirmed that current smoking is associated with an increased gastric cancer risk, however, only among individuals that are simultaneously sero-positive for the leading causal factor for gastric cancer, <I>H. pylori</I>.</P>
Chen, Yu,Wu, Fen,Saito, Eiko,Lin, Yingsong,Song, Minkyo,Luu, Hung N.,Gupta, Prakash C.,Sawada, Norie,Tamakoshi, Akiko,Shu, Xiao-Ou,Koh, Woon-Puay,Xiang, Yong-Bing,Tomata, Yasutake,Sugiyama, Kemmyo,Par Springer-Verlag 2017 Diabetologia Vol.60 No.6
<P>Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality.</P>
Michelle L. Baglia,Yong Cui,Tao Zheng,Gong Yang,Honglan Li,Mingrong You,Liling Xu,Harvey Murff,Yu-Tang Gao,Wei Zheng,Yong-Bing Xiang,Xiao-Ou Shu 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2
Purpose Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. Materials and Methods The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. Results After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. Conclusion Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.
Liao, Linda M,Friesen, Melissa C,Xiang, Yong-Bing,Cai, Hui,Koh, Dong-Hee,Ji, Bu-Tian,Yang, Gong,Li, Hong-Lan,Locke, Sarah J,Rothman, Nathaniel,Zheng, Wei,Gao, Yu-Tang,Shu, Xiao-Ou,Purdue, Mark P BMJ Publishing Group Ltd 2014 Occupational and environmental medicine Vol.71 No.suppl1
<P><B>Objectives</B></P><P>Epidemiologic studies of occupational lead exposure have suggested increased risks of cancers of the brain, kidney, lung, meninges, and stomach; however, the totality of the evidence is inconsistent. To clarify whether lead is a carcinogen, we investigated the relationship between occupational lead exposure and risks of these five cancer sites in two prospective cohort studies in Shanghai, China.</P><P><B>Method</B></P><P>Annual job/industry-specific estimates of lead fume and lead dust exposure were derived from a statistical model that combined expert ratings of lead intensity with inspection measurements collected by the Shanghai Centre for Disease Control and Prevention. The job/industry estimates were applied to the lifetime work histories of subjects from the Shanghai Women’s Health Study (73 363 participants) and the Shanghai Men’s Health Study (61 379 participants) to estimate cumulative exposure to lead dust and lead fume. Cohort-specific relative hazard rate ratios (RRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models and then pooled using a random effects meta-analysis model.</P><P><B>Results</B></P><P>We observed a statistically significant increased risk of meningioma among individuals with estimated occupational exposure to lead dust or fumes (RR=2.4, 95% CI:1.1–5.0), and in particular among those with an above-median cumulative exposure to dust or fumes (RR=3.1, 95% CI:1.3–7.4). We observed suggestive associations with lead exposure for cancers of the kidney (RR=1.4, 95% CI:0.9–2.3) and brain (RR=1.8, 95% CI:0.7–4.8), and null findings for cancers of the lung and stomach.</P><P><B>Conclusions</B></P><P>Our findings provide additional evidence that occupational lead exposure increases risk of meningioma.</P>