Person: Song, Mingyang
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Song
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Mingyang
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Song, Mingyang
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Publication Optimal dietary patterns for prevention of chronic disease(Springer Science and Business Media LLC, 2023-03) Giovannucci, Edward L; Wang, Peilu; Song, Mingyang; Eliassen, A; Wang, Molin; Fung, Teresa; Clinton, Steven K.; Rimm, Eric; Hu, Frank; Willet, Walter C.; Tabung, Fred; Giovannucci, EdwardMultiple dietary patterns have been associated with different diseases; however, their comparability to improve overall health is yet to be determined. In 205,852 healthcare professionals from three US cohorts followed for up to 32 years, we prospectively assessed two mechanism-based diets and six diets based on dietary recommendations in relation to major chronic disease, defined as a composite outcome of incident major cardiovascular disease, type 2 diabetes, and cancer. We demonstrated that adherence to a healthy diet was generally associated with a lower risk of major chronic disease (hazard ratio [HR] comparing the 90th to 10th percentile of dietary pattern scores: 0.58–0.80). Participants with low insulinemic (HR 0.58, 95% CI 0.57, 0.60), low inflammatory (HR 0.61, 95% CI 0.60, 0.63), or diabetes risk-reducing diet (HR 0.70, 95% CI 0.69, 0.72) had the largest risk reduction for incident major cardiovascular disease, type 2 diabetes, and cancer in composite and individually. Similar findings were observed across sex, and diverse ethnic groups. Our results suggest that dietary patterns that are associated with markers of hyperinsulinemia and inflammation and diabetes development may inform on future dietary guidelines for chronic disease prevention.Publication Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location(Nature Publishing Group, 2016) Mima, Kosuke; Cao, Yin; Chan, Andrew; Qian, Zhi Rong; Nowak, Jonathan; Masugi, Yohei; Shi, Yan; Song, Mingyang; da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Hamada, Tsuyoshi; Kosumi, Keisuke; Hanyuda, Akiko; Liu, Li; Kostic, Aleksandar; Giannakis, Marios; Bullman, Susan; Brennan, Caitlin; Milner, Danny; Baba, Hideo; Garraway, Levi; Meyerhardt, Jeffrey; Garrett, Wendy; Huttenhower, Curtis; Meyerson, Matthew; Giovannucci, Edward; Fuchs, Charles; Nakashima, Reiko; Ogino, ShujiObjectives: Evidence suggests a possible role of Fusobacterium nucleatum in colorectal carcinogenesis, especially in right-sided proximal colorectum. Considering a change in bowel contents and microbiome from proximal to distal colorectal segments, we hypothesized that the proportion of colorectal carcinoma enriched with F. nucleatum might gradually increase along the bowel subsites from rectum to cecum. Methods: A retrospective, cross-sectional analysis was conducted on 1,102 colon and rectal carcinomas in molecular pathological epidemiology databases of the Nurses’ Health Study and the Health Professionals Follow-up Study. We measured the amount of F. nucleatum DNA in colorectal tumor tissue using a quantitative PCR assay and equally dichotomized F. nucleatum-positive cases (high vs. low). We used multivariable logistic regression analysis to examine the relationship of a bowel subsite variable (rectum, rectosigmoid junction, sigmoid colon, descending colon, splenic flexure, transverse colon, hepatic flexure, ascending colon, and cecum) with the amount of F. nucleatum. Results: The proportion of F. nucleatum-high colorectal cancers gradually increased from rectal cancers (2.5% 4/157) to cecal cancers (11% 19/178), with a statistically significant linear trend along all subsites (P<0.0001) and little evidence of non-linearity. The proportion of F. nucleatum-low cancers was higher in rectal, ascending colon, and cecal cancers than in cancers of middle segments. Conclusions: The proportion of F. nucleatum-high colorectal cancers gradually increases from rectum to cecum. Our data support the colorectal continuum model that reflects pathogenic influences of the gut microbiota on neoplastic and immune cells and challenges the prevailing two-colon (proximal vs. distal) dichotomy paradigm.Publication Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival(Impact Journals LLC, 2016) Mima, Kosuke; Nowak, Jonathan; Qian, Zhi Rong; Cao, Yin; Song, Mingyang; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Hamada, Tsuyoshi; Zhang, Xuehong; Wu, Kana; Meyerhardt, Jeffrey; Baba, Hideo; Giovannucci, Edward; Chan, Andrew; Fuchs, Charles; Ogino, Shuji; Nakashima, ReikoColorectal tumors arise with genomic and epigenomic alterations through interactions between neoplastic cells, immune cells, and microbiota that vary along the proximal to distal axis of colorectum. Long interspersed nucleotide element-1 (LINE-1) hypomethylation in colorectal cancer has been associated with worse clinical outcome. Utilizing 1,317 colon and rectal carcinoma cases in two U.S.-nationwide prospective cohort studies, we examined patient survival according to LINE-1 methylation level stratified by tumor location. Cox proportional hazards model was used to assess a statistical interaction between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, and KRAS, BRAF, and PIK3CA mutations. A statistically significant interaction was found between LINE-1 methylation level and tumor location in colorectal cancer-specific mortality analysis (Pinteraction = 0.011). The association of LINE-1 hypomethylation with higher colorectal cancer-specific mortality was stronger in proximal colon cancers (multivariable hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.21 to 2.28) than in distal colon cancers (multivariable HR, 1.18; 95% CI, 0.81 to 1.72) or rectal cancers (multivariable HR, 0.87; 95% CI, 0.57 to 1.34). Our data suggest the interactive effect of LINE-1 methylation level and colorectal cancer location on clinical outcome.Publication Adiposity and Cancer Risk: A Life Course Approach(2015-04-28) Song, Mingyang; Giovannucci, Edward L.; Willett, Walter C.; Spiegelman, Donna; Hu, Frank B.Obesity is a risk factor for several cancers, including colorectal cancer (CRC). I and my colleagues investigated adulthood weight change and body fat distribution and its change in relation to CRC risk in the Nurses’ Health Study and Health Professionals Follow-up Study. We also identified distinct trajectories of body fatness across the lifespan using a group-based modeling approach and then compared cancer risk across these trajectories. We found that weight gain from early adulthood to baseline was associated with an increased risk of CRC, whereas weight loss was associated with a lower risk. The association was stronger in men than in women. High waist circumference, hip circumference and waist-to-hip ratio were all associated with a higher risk of CRC in men, even after adjusting for body mass index. The associations were weaker in women. Ten-year gain of waist circumference, independent of weight change, was positively associated with CRC risk in men, but not in women. We identified 5 distinct adiposity trajectories across the lifespan: lean-stable, lean-moderate increase, lean-marked increase, medium-stable, and heavy-marked increase. Compared to women in the lean-stable group, those in the lean-marked increase and heavy-marked increase groups had a higher risk of esophageal adenocarcinoma and cancers of the colorectum, pancreas, kidney, and endometrium. Postmenopausal breast cancer risk was inversely associated with early-life adiposity, but was positively associated with late-life adiposity. In men, increased body fatness at any life period was associated with a higher risk of esophageal adenocarcinoma and colorectal cancer; compared to men in the lean-stable group, those in the heavy-marked increase group had a higher risk of pancreatic cancer, but lower risk of advanced prostate cancer. The trajectory-cancer associations were generally stronger for non-smokers and women who did not use menopausal hormone therapy. In conclusion, weight gain from early to middle adulthood was positively, and weight loss was negatively associated with CRC risk. Abdominal adiposity was positively associated with CRC risk and this association was stronger and independent of overall obesity in men than in women. Adiposity trajectories throughout life were associated with cancer risk and the pattern of associations varied by sex and cancer site.Publication Soluble tumour necrosis factor receptor type II and survival in colorectal cancer(Nature Publishing Group, 2016) Babic, Ana; Shah, Sonali M; Song, Mingyang; Wu, Kana; Meyerhardt, Jeffrey A; Ogino, Shuji; Yuan, Chen; Giovannucci, Edward; Chan, Andrew; Stampfer, Meir; Fuchs, Charles S; Ng, KimmieBackground: Chronic inflammation may play a role in colorectal cancer (CRC) pathogenesis. The relationship between soluble tumour necrosis factor receptor type II (sTNF-RII) and survival among CRC patients is not well defined. Methods: We prospectively evaluated the association between pre-diagnosis plasma levels of sTNF-RII and mortality in 544 CRC patients from the Nurses' Health Study and Health Professionals Follow-Up Study diagnosed from 1990 to 2010. Primary and secondary end points were overall and CRC-specific mortality, respectively. Cox proportional hazards models were used to calculate multivariate hazard ratios for mortality. Results: Higher sTNF-RII levels were significantly associated with increased overall mortality (multivariate HR=1.48, 95% CI 1.02–2.16, P-trend=0.006), but not with CRC-specific mortality (HR=1.23, 95% CI 0.72–2.08, P-trend=0.34). In subgroup analyses, among regular aspirin users, those with higher sTNF-RII levels had an adjusted HR of 0.52 (95% CI 0.20–1.33) for overall mortality compared with those with lower sTNF-RII levels, whereas among nonregular aspirin users the adjusted HR was 2.26 (95% CI 1.23–4.01, P for interaction=0.53). Conclusions: Among CRC patients, higher sTNF-RII levels are associated with a significant increase in overall mortality, but not CRC-specific mortality. The role of inflammation and anti-inflammatory medications in survival of CRC patients warrants further exploration.Publication A Prospective Analysis of Meat Mutagens and Colorectal Cancer in the Nurses’ Health Study and Health Professionals Follow-up Study(National Institute of Environmental Health Sciences, 2016) Le, Ngoan; Michels, Fernanda Alessandra Silva; Song, Mingyang; Zhang, Xuehong; Bernstein, Adam M.; Giovannucci, Edward; Fuchs, Charles; Ogino, Shuji; Chan, Andrew; Sinha, Rashmi; Willett, Walter; Wu, KanaBackground: Heterocyclic amines (HCAs) in cooked meats may play a role in colorectal cancer (CRC) development. Objectives: We aimed to prospectively examine the association between estimated intakes of HCAs and meat-derived mutagenicity (MDM) in two cohorts of health professionals, the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS). Methods: In 29,615 men and 65,875 women, intake of the HCAs 2-amino-3,8-dimethylimidazo(4,5-j)quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo(4,5-f)quinoxaline (DiMeIQx), and MDM was estimated using a 1996 cooking questionnaire, the 1994 food frequency questionnaire, and an online database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and to adjust for potential confounders. Estimates for both cohorts were pooled using random-effects meta-analysis. Results: Between 1996 and 2010, 418 male and 790 female CRC cases were identified. Meat mutagen intake was not statistically significantly associated with risk of CRC [highest vs. lowest quintile, pooled HR (95% CI) for MeIQx: 1.12 (0.93, 1.34), p for trend 0.23; PhIP: 1.10 (0.90, 1.33), p for trend 0.35; MDM: 1.03 (0.86, 1.24), p for trend 0.75] or subtypes of CRC defined by tumor location (proximal or distal colon, or rectum). When analyzed by source of meat, PhIP from red but not from white meat was nonsignificantly positively associated with CRC and significantly positively associated with proximal cancers [HR (95% CI) per standard deviation increase of log-transformed intake: PhIP red meat: CRC: 1.06 (0.99, 1.12), proximal: 1.11 (1.02, 1.21); PhIP white meat: CRC: 0.99 (0.94, 1.04), proximal: 1.00 (0.93, 1.09)]. Conclusions: Estimated intakes of meat mutagens were not significantly associated with CRC risk over 14 years of follow-up in the NHS and HPFS cohorts. Results for PhIP from red but not from white meat warrant further investigation. Citation: Le NT, Michels FA, Song M, Zhang X, Bernstein AM, Giovannucci EL, Fuchs CS, Ogino S, Chan AT, Sinha R, Willett WC, Wu K. 2016. A prospective analysis of meat mutagens and colorectal cancer in the Nurses’ Health Study and Health Professionals Follow-up Study. Environ Health Perspect 124:1529–1536; http://dx.doi.org/10.1289/EHP238Publication Processed and Unprocessed Red Meat and Risk of Colorectal Cancer: Analysis by Tumor Location and Modification by Time(Public Library of Science, 2015) Bernstein, Adam M.; Song, Mingyang; Zhang, Xuehong; Pan, An; Wang, Molin; Fuchs, Charles; Le, Ngoan; Chan, Andrew; Willett, Walter; Ogino, Shuji; Giovannucci, Edward; Wu, KanaAlthough the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses’ Health Study (n = 87,108 women, 1980–2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986–2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01–1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09–1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68–0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92–1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.Publication Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate(Wiley, 2016-05-10) Hanyuda, Akiko; Ogino, Shuji; Qian, Zhi Rong; Nakashima, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Wu, Kana; Meyerhardt, Jeffrey; Chan, Andrew; Fuchs, Charles S.; Giovannucci, Edward; Cao, YinHigher body mass index (BMI), higher body adiposity, and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses’ Health Study (1980–2010) and the Health Professionals Follow-up Study (1986–2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn’s-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend<0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (Pheterogeneity>0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.Publication Overview of the Microbiome Among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies(Springer Science and Business Media LLC, 2021-04-21) Song, Mingyang; Everett, Christine; Li, Chengchen; Wilkinson, Jeremy; Nguyen, Long; McIver, Lauren; Ivey, Kerry; Izard, Jacques; Palacios, Natalia; Eliassen, A; Willett, Walter; Ascherio, Alberto; Sun, Qi; Tworoger, Shelley; Chang, Andrew; Garrett, Wendy; Huttenhower, Curtis; Rimm, EricA lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses’ Health Study II cohort (the Microbiome among Nurses, or Micro-N study). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort's ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way towards development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out.Publication A Framework for Microbiome Science in Public Health(Nature / Springer, 2021-04-05) Wilkinson, Jeremy E.; Franzosa, Eric; Everett, Christine; Li, Chengchen; Hu, Frank; Wirth, Dyann; Song, Mingyang; Chan, Andrew; Rimm, Eric; Garrett, Wendy; Huttenhower, CurtisHuman microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation, and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners, and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here, we provide an outline of considerations for research, education, interpretation, and scientific communication of the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are opportunities both for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live cell therapies, and fecal microbiota transplants.