Browsing by Author "Wang, Molin"

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    Calcium Intake and Risk of Colorectal Cancer According to Tumor-infiltrating T Cells
    (AACR, 2019-05) Yang, Wanshui; Liu, Li; Keum, NaNa; Qian, Zhi Rong; Nowak, Jonathan A.; Hamada, Tsuyoshi; Song, Mingyang; Cao, Yin; Nosho, Katsuhiko; Smith-Warner, Stephanie A.; Zhang, Sui; Masugi, Yohei; Ng, Kimmie; Kosumi, Keisuke; Ma, Yanan; Garrett, Wendy S.; Wang, Molin; Nan, Hongmei; Giannakis, Marios; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Nishihara, Reiko; Wu, Kana; Giovannucci, Edward L.; Ogino, Shuji; Zhang, Xuehong; Epidemiology, School of Public Health
    Calcium intake has been associated with a lower risk of colorectal cancer. Calcium signaling may enhance T-cell proliferation and differentiation, and contribute to T-cell–mediated antitumor immunity. In this prospective cohort study, we investigated the association between calcium intake and colorectal cancer risk according to tumor immunity status to provide additional insights into the role of calcium in colorectal carcinogenesis. The densities of tumor-infiltrating T-cell subsets [CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ cell] were assessed using IHC and computer-assisted image analysis in 736 cancer cases that developed among 136,249 individuals in two cohorts. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. Total calcium intake was associated with a multivariable HR of 0.55 (comparing ≥1,200 vs. <600 mg/day; 95% CI, 0.36–0.84; Ptrend = 0.002) for CD8+ T-cell–low but not for CD8+ T-cell–high tumors (HR = 1.02; 95% CI, 0.67–1.55; Ptrend = 0.47). Similarly, the corresponding HRs (95% CIs) for calcium for low versus high T-cell–infiltrated tumors were 0.63 (0.42–0.94; Ptrend = 0.01) and 0.89 (0.58–1.35; Ptrend = 0.20) for CD3+; 0.58 (0.39–0.87; Ptrend = 0.006) and 1.04 (0.69–1.58; Ptrend = 0.54) for CD45RO+; and 0.56 (0.36–0.85; Ptrend = 0.006) and 1.10 (0.72–1.67; Ptrend = 0.47) for FOXP3+, although the differences by subtypes defined by T-cell density were not statistically significant. These potential differential associations generally appeared consistent regardless of sex, source of calcium intake, tumor location, and tumor microsatellite instability status. Our findings suggest a possible role of calcium in cancer immunoprevention via modulation of T-cell function.
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    Coffee Intake of Colorectal Cancer Patients and Prognosis According to Histopathologic Lymphocytic Reaction and T-Cell Infiltrates
    (Elsevier, 2022) Ugai, Tomotaka; Haruki, Koichiro; Väyrynen, Juha P.; Borowsky, Jennifer; Fujiyoshi, Kenji; Lau, Mai Chan; Akimoto, Naohiko; Zhong, Rong; Kishikawa, Junko; Arima, Kota; Shi, Shan-shan; Zhao, Melissa; Fuchs, Charles S.; Zhang, Xuehong; Giannakis, Marios; Song, Mingyang; Nan, Hongmei; Meyerhardt, Jeffrey A.; Wang, Molin; Nowak, Jonathan A.; Ogino, Shuji; Community and Global Health, Richard M. Fairbanks School of Public Health
    Given previous biological evidence of immunomodulatory effects of coffee, we hypothesized that the association between coffee intake of colorectal cancer patients and survival differs by immune responses. Using a molecular pathological epidemiology database of 4,465 incident colorectal cancer cases, including 1,262 cases with molecular data, in the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined the association between coffee intake of colorectal cancer patients and survival in strata of levels of histopathologic lymphocytic reaction and T-cell infiltrates in tumor tissue. We did not observe a significant association of coffee intake with colorectal cancer-specific mortality [multivariable-adjusted hazard ratio (HR) for one cup increase of coffee intake per day, 0.93; 95% confidence interval (CI), 0.84-1.03]. Although statistical significance was not reached at the stringent level (α=0.005), the association of coffee intake with colorectal cancer-specific mortality differed by Crohn's-like lymphoid reaction (Pinteraction=.007). Coffee intake was associated with lower colorectal cancer-specific mortality in patients with high Crohn's-like reaction (multivariable HR for one cup increase of coffee intake per day, 0.55; 95% CI, 0.37–0.81; Ptrend=.002), but not in patients with intermediate Crohn's-like reaction (the corresponding HR, 1.02; 95% CI, 0.72–1.44) or negative/low Crohn's-like reaction (the corresponding HR, 0.95; 95% CI, 0.83–1.07). The associations of coffee intake with colorectal cancer-specific mortality did not significantly differ by levels of other lymphocytic reaction or any T-cell subset (Pinteraction>.18). There is suggestive evidence for differential prognostic effects of coffee intake by Crohn’s-like lymphoid reaction in colorectal cancer.
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    Plasma concentrations of leptin at mid-pregnancy are associated with gestational weight gain among pregnant women in Tanzania: a prospective cohort study
    (BMC, 2021-10-06) Wang, Dongqing; Darling, Anne Marie; McDonald, Chloe R.; Perumal, Nandita; Liu, Enju; Wang, Molin; Aboud, Said; Urassa, Willy; Conroy, Andrea L.; Hayford, Kyla T.; Liles, W. Conrad; Kain, Kevin C.; Fawzi, Wafaie W.; Pediatrics, School of Medicine
    Background: Gestational weight gain (GWG) has critical implications for maternal and child health. Inflammation and angiogenesis are implicated in various aspects of maternal metabolism that may play a role in gestational weight gain. The associations of inflammatory, angiogenic, and metabolic pathways with GWG are yet to be elucidated. This study evaluated associations between a panel of inflammatory, angiogenic, and metabolic proteins measured in mid-pregnancy and gestational weight gain. Methods: Pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. The participants were enrolled at mid-pregnancy (12 to 27 weeks of gestation) and followed up until delivery. This analysis focused on a cohort of 1002 women who were primigravid, had singleton live births, had longitudinal measures of gestational weight, and whose mid-pregnancy plasma samples underwent analysis for 18 proteins. Results: Higher plasma concentrations of leptin (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 10.24; 95% CI 3.31, 17.16; p-trend = 0.003) and chitinase-3-like protein-1 (CH3L1) (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 7.02; 95% CI 0.31, 13.72; p-trend = 0.007) were associated with greater GWG in a dose-response pattern. Higher leptin concentrations were associated with a lower risk of inadequate GWG (risk ratio comparing highest with lowest quartiles: 0.77; 95% CI 0.65, 0.91; p-trend = 0.001) and a higher risk of excessive GWG (risk ratio comparing highest with lowest quartiles: 1.57; 95% CI 1.03, 2.39; p-trend = 0.03). Higher CH3L1 concentrations were associated with a higher risk of excessive GWG (p-trend = 0.007). The associations of leptin and CH3L1 with inadequate GWG were stronger during the second than the third trimester. The other 16 proteins examined were not significantly associated with GWG. Conclusions: Mid-pregnancy plasma leptin concentrations may be associated with GWG and have clinical predictive utility in identifying women at a higher risk of inadequate or excessive gestational weight gain.
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    Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199
    (ASCO, 2014) Adams, Sylvia; Gray, Robert J.; Demaria, Sandra; Goldstein, Lori; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Wang, Molin; Jones, Vicky E.; Saphner, Thomas J.; Wolff, Antonio C.; Wood, William C.; Davidson, Nancy E.; Sledge, George W.; Sparano, Joseph A.; Badve, Sunil S.; Pathology and Laboratory Medicine, School of Medicine
    Purpose Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and Methods Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. Results The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. Conclusion In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.