Browsing by Author "Zhang, Xuehong"

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    Body Mass Index Trajectories, Weight Gain, and Risks of Liver and Biliary Tract Cancers
    (Oxford University Press, 2022-08-12) Yang, Wanshui; Zeng, Xufen; Petrick, Jessica L.; Danford, Christopher J.; Florio, Andrea A.; Lu, Bing; Nan, Hongmei; Ma, Jiantao; Wang, Liang; Zeng, Hongmei; Sudenga, Staci L.; Campbell, Peter T.; Giovannucci, Edward; McGlynn, Katherine A.; Zhang, Xuehong; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). Methods: We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). BMI was self-reported at ages 20, 50, and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 15.9 years among 138,922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI does not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 had increased risks of liver cancer (HR = 2.03, 95% CI: 1.26-3.28) and BTC (HR = 1.99, 95% CI: 1.16-3.39). Compared to participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI: 1.55-4.04) and BTC (HR = 1.83, 95% CI: 1.03-3.22). Compared to adults with stable weight (+/-5kg) between age 20 to 50 years, weight gain ≥20 kg between ages 20 to 50 years had higher HRs of 2.24 (95%CI: 1.40-3.58) for liver cancer and 1.86 (95% CI: 1.12-3.09) for BTC. Conclusions: Being overweight/obese at age 20, and BMI trajectories that result in being overweight and/or obese, may increase risk for both liver cancer and BTC.
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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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    Insulinemic Potential of Lifestyle Is Inversely Associated with Leukocyte Mitochondrial DNA Copy Number in US White Adults
    (Elsevier, 2020-08-01) Yang, Keming; Forman, Michele R.; Monahan, Patrick O.; Graham, Brett H.; Chan, Andrew T.; Zhang, Xuehong; De Vivo, Immaculata; Giovannucci, Edward L.; Tabung, Fred K.; Nan, Hongmei; Epidemiology, School of Public Health
    Background: Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. Objectives: Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. Methods: This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses' Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. Results: We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows: Q1: 0.14 ± 0.05; Q2: 0.04 ± 0.06; Q3: 0.008 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows: Q1: 0.25 ± 0.09; Q2: 0.23 ± 0.09; Q3: 0.07 ± 0.09; Q4: 0.02 ± 0.09; and Q5: -0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows: Q1: 0.16 ± 0.05; Q2: 0.07 ± 0.05; Q3: 0.01 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.05 ± 0.05 (P-trend = 0.0004). Conclusions: Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.
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    Pre-Diagnostic Telomere Length and Colorectal Cancer Risk
    (Elsevier, 2022) Yang, Keming; Prescott, Jennifer; Hazra, Aditi; Meyerhardt, Jeffrey A.; Zhang, Xuehong; De Vivo, Immaculata; Chan, Andrew T.; Du, Mengmeng; Giovannucci, Edward L.; Nan, Hongmei; Community and Global Health, Richard M. Fairbanks School of Public Health
    Background: Progressive telomere shortening may be related to genomic instability and carcinogenesis. Prospective evidence relating telomere length (TL) with colorectal cancer (CRC) risk has been limited and inconsistent. Methods: We examined the association between pre-diagnostic peripheral blood leukocyte TL and CRC risk in two matched case-control studies nested within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Relative leukocyte TL was measured using qPCR among 356 incident CRC cases and 801 controls (NHS: 186/465, HPFS: 170/336). Results: We did not find a significant association between pre-diagnostic TL and CRC risk [in all participants, multivariable-adjusted odds ratio (OR) (95% CI) for TL Quartile 1 (shortest) vs. Quartile 4 (longest) = 1.36 (0.85, 2.17), P-trend = 0.27; OR (95% CI) per 1 SD decrease in TL = 1.12 (0.92, 1.36)]. Conclusions: Our prospective analysis did not support a significant association between pre-diagnostic leukocyte TL and CRC risk.
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    Rice consumption and cancer incidence in US men and women
    (Wiley Blackwell (John Wiley & Sons), 2016-02-01) Zhang, Ran; Zhang, Xuehong; Wu, Kana; Wu, Hongyu; Sun, Qi; Hu, Frank B.; Han, Jiali; Willett, Walter C.; Giovannucci, Edward L.; Department of Dermatology, IU School of Medicine
    While both the 2012 and 2014 Consumer Reports concerned arsenic levels in US rice, no previous study has evaluated long-term consumption of total rice, white rice and brown rice in relation to risk of developing cancers. We investigated this in the female Nurses' Health Study (1984-2010), and Nurses' Health Study II (1989-2009), and the male Health Professionals Follow-up Study (1986-2008), which included a total of 45,231 men and 160,408 women, free of cancer at baseline. Validated food frequency questionnaires were used to measure rice consumption at baseline and repeated almost every 4 years thereafter. We employed Cox proportional hazards regression model to estimate multivariable relative risks (RRs) and 95% confidence intervals (95% CIs). During up to 26 years of follow-up, we documented 31,655 incident cancer cases (10,833 in men and 20,822 in women). Age-adjusted results were similar to multivariable-adjusted results. Compared to participants with less than one serving per week, the multivariable RRs of overall cancer for individuals who ate at least five servings per week were 0.97 for total rice (95% CI: 0.85-1.07), 0.87 for white rice (95% CI: 0.75-1.01), and 1.17 for brown rice (95% CI: 0.90-1.26). Similar non-significant associations were observed for specific sites of cancers including prostate, breast, colon and rectum, melanoma, bladder, kidney, and lung. Additionally, the null associations were observed among European Americans and non-smokers, and were not modified by BMI. Long-term consumption of total rice, white rice or brown rice was not associated with risk of developing cancer in US men and women.