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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1735-1735
    Abstract: Introduction: Epidemiological findings on the association between fruit and vegetable consumption and gastric cancer risk remain inconsistent, resulting in the designation of fruits and vegetables as “probable” and “possible” respectively, but not “convincing”, protective factors. However, intervention studies provide support for the effect of micronutrient supplementation in the prevention of gastric cancer and its precursor lesions, though the effects remain less substantial than for Helicobacter pylori (H. pylori) eradication. Objective: To ascertain the association between fruit and vegetable intake and non-cardia gastric cancer incidence with adjustment for H. pylori within East Asian cohort studies. Methods: The present analysis includes 1970 participants (810 prospectively ascertained non-cardia gastric cancer cases with 1160 matched controls) from 5 cohort studies in the Helicobacter pylori Biomarker Cohort Consortium. These cohorts collected blood samples as well as demographic, lifestyle, and dietary data at baseline. Pre-diagnostic antibody levels to 15 H. pylori proteins were assessed using multiplex serology. Conditional logistic regression, adjusting for total energy intake, smoking, and H. pylori status, was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer risk across cohort- and sex-specific quartiles of fruit and vegetable intake. Results: Increasing fruit intake was significantly associated with decreasing risk of non-cardia gastric cancer, so that individuals in the highest quartile of fruit consumption had a 29% reduced odds of gastric cancer, compared to individuals in the lowest quartile (OR = 0.71, 95% CI, 0.52-0.95, P for trend = 0.02). Compared to CagA-positive H. pylori low fruit consumers, the strongest inverse association of gastric cancer risk was amongst those high fruit consumers without evidence of H. pylori antibodies (OR = 0.12, 95% CI: 0.06-0.25), whereby the inverse association by increasing fruit consumption was attenuated among individuals infected with CagA-positive H. pylori (OR = 0.82, 95% CI: 0.66-1.03). We observed a weaker, non-dose-response suggestion of an inverse association of vegetable intake with non-cardia gastric cancer risk. Conclusions: To our knowledge, this is the largest prospective study in the high-risk region of East Asia to examine the association of fruit and vegetable consumption with non-cardia gastric cancer risk adjusted for H. pylori. We have found that high fruit intake may play a role in decreasing risk of non-cardia gastric cancer, even after adjustment for H. pylori subtype-specific infection. Funding: R01 CA174853 Citation Format: Tianyi Wang, Hui Cai, Shizuka Sasazuki, Shoichiro Tsugane, Wei Zheng, Eo Rin Cho, Sun Ha Jee, Angelika Michel, Michael Pawlita, Yong-Bing Xiang, Yu-Tang Gao, Xiao-Ou Shu, Weicheng You, Meira Epplein. Fruit and vegetable consumption and risk of gastric cancer: a prospective nested case-control study in China, Japan and Korea. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1735.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 2
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    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. LB-361-LB-361
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. LB-361-LB-361
    Abstract: Background: The colonic opportunist Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) has been hypothesized to be associated with colorectal cancer (CRC). A recent case-control study (Butt et al., Int J Cancer. 2015 doi: 10.1002/ijc.29914.) showed an association of high antibody levels to S. gallolyticus pilus proteins with prevalent CRC. However, no study has yet explored this association in a prospective study. Objective: To determine whether antibody responses to S. gallolyticus are associated with CRC risk 1 to 8 (median 3) years before diagnosis. Methods: A case-control study was nested within the prospective Southern Community Cohort Study (SCCS) which has enrolled 86,000 men and women between 2002 and 2009 primarily from community health centers (CHC). Participants included here comprised 181 incident CRC cases that were identified until end of 2011 and 348 controls matched by sex, age, race, menopausal status, CHC site and date of blood collection. Antibodies to 11 recombinant affinity-purified S. gallolyticus proteins, including 4 S. gallolyticus pilus proteins, were quantified by multiplex serology. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Results: Overall, there was no significant association of high antibody levels to any S. gallolyticus protein (OR: 1.11, 95% CI: 0.77-1.58) or any pilus protein (OR: 1.34, 95% CI: 0.91-1.96) with CRC. However, when stratifying by stage at diagnosis, the association with high antibody levels to any pilus protein was significant for CRC diagnosed with regional or distant stage (OR: 1.68, 95% CI: 1.01-2.78), whereby no association was found for localized CRC (OR: 0.85, 95% CI: 0.45-1.63). Epplein et al. showed that seropositivity to the gastric cancer virulence factor Helicobacter pylori (H. pylori) VacA is significantly associated with CRC (Epplein et al., Cancer Epidemiol Biomarkers Prev. 22(11):1964-74. 2013). Under the assumption that different bacteria may be involved in CRC and that they may interact with each other, we performed an analysis stratified by H. pylori VacA serostatus. Here, the association with high antibody levels to any S. gallolyticus protein with CRC was significant among H. pylori VacA negative individuals (OR: 2.40, 95% CI: 1.12-5.15) but absent among H. pylori VacA positives (OR: 0.83, 95% CI: 0.54-1.29; interaction p = 0.019). Conclusion: This prospective study failed to find a significant overall association of antibodies to S. gallolyticus proteins with CRC. However, among individuals (and their matched controls) who would go on to be diagnosed with later stage tumors, seropositivity to S. gallolyticus was associated with a significant 1.7-fold increase in risk for CRC. In addition we found an interaction between seropositivity to H. pylori VacA with S. gallolyticus in the association with CRC, whereby the increase in risk for seropositivity to S. gallolyticus was seen only among individuals not also infected with VacA-positive H. pylori. This finding supports the idea that different bacteria are involved in CRC and that they may influence each other in their association. Further research with larger study sizes is needed to examine the outcome by both time from blood collection to diagnosis and stage to more precisely shed light on the timing of the association, as well as to consider interaction with infection by other bacteria. Citation Format: Julia Butt, Michael Pawlita, Meira Epplein. Serology of Streptococcus gallolyticus subsp. gallolyticus and risk of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-361.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 3
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 27, No. 10 ( 2018-10-01), p. 1186-1194
    Abstract: Background: Antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG) proteins, especially pilus protein Gallo2178, have been consistently associated with colorectal cancer risk. Previous case–control studies and prospective studies with up to 8 years of follow-up, however, were unable to decipher the temporality of antibody responses to SGG in the context of the long-term multistep development of colorectal cancer. In this study, we analyzed a large U.S. colorectal cancer cohort consortium with follow-up beyond 10 years for antibody responses to SGG. Methods: We applied multiplex serology to measure antibody responses to 9 SGG proteins in participants of 10 prospective U.S. cohorts (CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS, and WHI) including 4,063 incident colorectal cancer cases and 4,063 matched controls. Conditional logistic regression was used to assess whether antibody responses to SGG were associated with colorectal cancer risk, overall and by time between blood draw and diagnosis. Results: Colorectal cancer risk was increased among those with antibody responses to Gallo2178, albeit not statistically significant [OR, 1.23; 95% confidence interval (CI), 0.99–1.52]. This association was stronger for cases diagnosed & lt;10 years after blood draw (OR, 1.40; 95% CI, 1.09–1.79), but was not found among cases diagnosed ≥10 years after blood draw (OR, 0.79; 95% CI, 0.50–1.24). Conclusions: In a large cohort consortium, we reproduced the association of antibody responses to SGG Gallo2178 with colorectal cancer risk for individuals diagnosed within 10 years after blood draw. Impact: This timing-specific finding suggests that antibody responses to SGG are associated with increased colorectal cancer risk only after tumorigenesis has begun. Cancer Epidemiol Biomarkers Prev; 27(10); 1186–94. ©2018 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2272-2272
    Abstract: Background. Previous studies suggest that a stable end-product of prostaglandin E2, the urinary metabolite PGE-M, is excreted in the urine and can be used as an index of systemic prostaglandin E2 (PGE2) production. In the present study we investigate the PGE-M, Helicobacter pylori (H. pylori), and gastric cancer association. Methods. The present analysis included 359 prospectively ascertained gastric cancer cases and 700 individually matched controls from two population-based prospective cohort studies, the Shanghai Women’s Health Study and Shanghai Men’s Health Study. Urinary PGE-M was measured by a liquid chromatography/tandem mass spectrometric method. Sero-positivity to 15 H. pylori recombinantly expressed fusion proteins was detected by H. pylori multiplex serology. Results. Adjusting for H. pylori, increasing PGE-M was associated with higher risk of gastric cancer (Quartile 4 vs. 1, OR=1.76, 95% CI: 1.17-2.66, Ptrend =0.004). This association remained after excluding those diagnosed within two years from sample collection (OR=1.73, 95% CI: 1.12-2.65, Ptrend =0.007). However it was no longer present among individuals with 10 or more years of follow-up (2-4.9 years, OR=3.15, 95% CI: 1.11-8.91; 5-9.9 years, OR=2.23, 95% CI: 1.22-4.06; ≥10 years, OR=0.73, 95% CI: 0.31-1.70). The association of PGE-M with gastric cancer risk was not modified by H. pylori status, but added predictive ability beyond H. pylori; compared to H. pylori-negative individuals with below-median PGE-M levels, H. pylori-positive individuals with above-median PGE-M levels had a 5-fold increase in the odds ratio of gastric cancer (OR=5.08, 95% CI: 2.47-10.43). Conclusion. In China, higher PGE-M levels may indicate an increased risk of gastric cancer independent of the risk conferred by H. pylori infection status, particularly for cancers diagnosed within 10 years of sample collection. Citation Format: Tianyi Wang, Hui Cai, Wei Zheng, Angelika Michel, Michael Pawlita, Ginger Milne, Yong-Bing Xiang, Yu-Tang Gao, Hong-Lan Li, Nathaniel Rothman, Qing Lan, Xiao-Ou Shu, Meira Epplein. A prospective study of urinary prostaglandin E2 metabolite, Helicobacter pylori antibodies, and gastric cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2272. doi:10.1158/1538-7445.AM2017-2272
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 5
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    Online Resource
    Public Library of Science (PLoS) ; 2019
    In:  PLOS Pathogens Vol. 15, No. 8 ( 2019-8-8), p. e1007861-
    In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 15, No. 8 ( 2019-8-8), p. e1007861-
    Type of Medium: Online Resource
    ISSN: 1553-7374
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2019
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  • 6
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 45, No. 3 ( 2016-06), p. 774-781
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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  • 7
    In: Gastroenterology, Elsevier BV, Vol. 156, No. 1 ( 2019-01), p. 175-186.e2
    Type of Medium: Online Resource
    ISSN: 0016-5085
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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  • 8
    In: Digestive Diseases and Sciences, Springer Science and Business Media LLC, Vol. 63, No. 10 ( 2018-10), p. 2765-2772
    Type of Medium: Online Resource
    ISSN: 0163-2116 , 1573-2568
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
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  • 9
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 64, No. 10 ( 2017-05-15), p. 1380-1386
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2002229-3
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  • 10
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 27, No. 12 ( 2018-12-01), p. 1472-1479
    Abstract: Helicobacter pylori is the leading cause of gastric cancer, yet the majority of infected individuals will not develop neoplasia. Previously, we developed and replicated serologic H. pylori 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. Methods: This cross-sectional study included 1,402 individuals from Linqu County screened by upper endoscopy. H. pylori 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. Results: 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 H. pylori, 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, Pdifference = 0.0002). Conclusions: The present study of prevalent precancerous gastric lesions provides support for two new serum biomarkers of gastric cancer risk, Omp and HP 0305. Impact: 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.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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