Baiyu Yang

Active Smoking and Mortality Among Colorectal Cancer Survivors: The Cancer Prevention Study II Nutrition Cohort

PURPOSE Active smoking is associated with higher colorectal cancer risk, but its association with survival after colorectal cancer diagnosis is unclear. We investigated associations of smoking, before and after diagnosis, with all-cause and colorectal cancer-specific mortality among colorectal cancer survivors. PATIENTS AND METHODS From a cohort of adults who were initially free of colorectal cancer, we identified 2,548 persons diagnosed with invasive, nonmetastatic colorectal cancer between baseline (1992 or 1993) and 2009. Vital status and cause of death were determined through 2010. Smoking was self-reported on the baseline questionnaire and updated in 1997 and every 2 years thereafter. Postdiagnosis smoking information was available for 2,256 persons (88.5%). RESULTS Among the 2,548 colorectal cancer survivors, 1,074 died during follow-up, including 453 as a result of colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, prediagnosis current smoking was associated with higher all-cause mortality (relative risk [RR], 2.12; 95% CI, 1.65 to 2.74) and colorectal cancer-specific mortality (RR, 2.14; 95% CI, 1.50 to 3.07), whereas former smoking was associated with higher all-cause mortality (RR, 1.18; 95% CI, 1.02 to 1.36) but not with colorectal cancer-specific mortality (RR, 0.89; 95% CI, 0.72 to 1.10). Postdiagnosis current smoking was associated with higher all-cause (RR, 2.22; 95% CI, 1.58 to 3.13) and colorectal cancer-specific mortality (RR, 1.92; 95% CI, 1.15 to 3.21), whereas former smoking was associated with all-cause mortality (RR, 1.21; 95% CI, 1.03 to 1.42). CONCLUSION This study adds to the existing evidence that cigarette smoking is associated with higher all-cause and colorectal cancer-specific mortality among persons with nonmetastatic colorectal cancer.

Calcium, Vitamin D, Dairy Products, and Mortality Among Colorectal Cancer Survivors: The Cancer Prevention Study-II Nutrition Cohort

PURPOSE Higher calcium, vitamin D, and dairy product intakes are associated with lower colorectal cancer incidence, but their impacts on colorectal cancer survival are unclear. We evaluated associations of calcium, vitamin D, and dairy product intakes before and after colorectal cancer diagnosis with all-cause and colorectal cancer-specific mortality among colorectal cancer patients. PATIENTS AND METHODS This analysis included 2,284 participants in a prospective cohort who were diagnosed with invasive, nonmetastatic colorectal cancer after baseline (1992 or 1993) and up to 2009. Mortality follow-up was through 2010. Prediagnosis risk factor information was collected on the baseline questionnaire. Postdiagnosis information was collected via questionnaires in 1999 and 2003 and was available for 1,111 patients. RESULTS A total of 949 participants with colorectal cancer died during follow-up, including 408 from colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, postdiagnosis total calcium intake was inversely associated with all-cause mortality (relative risk [RR] for those in the highest relative to the lowest quartiles, 0.72; 95% CI, 0.53-0.98; Ptrend = .02) and associated with marginally statistically significant reduced colorectal cancer-specific mortality (RR, 0.59; 95% CI, 0.33 to 1.05; Ptrend = .01). An inverse association with all-cause mortality was also observed for postdiagnosis milk intake (RR, 0.72; 95% CI, 0.55 to 0.94; Ptrend = .02), but not vitamin D intake. Prediagnosis calcium, vitamin D, and dairy product intakes were not associated with any mortality outcomes. CONCLUSION Higher postdiagnosis intakes of total calcium and milk may be associated with lower risk of death among patients with nonmetastatic colorectal cancer.

Successful Enrollment in Text4Baby More Likely With Higher Health Literacy

Adequate health literacy is vital for understanding and using health information. The authors assessed the health literacy of pregnant women and mothers of children under the age of 1 year and their success in self-enrolling in the Text4Baby health message program: 468 pregnant women and mothers of children under the age of 1 year completed an in-person baseline survey, including the Newest Vital Sign health literacy assessment, at 2 Metro-Atlanta Women, Infants, and Children clinics. They were asked to self-enroll in the Text4Baby message program and were later contacted by phone to see whether they had attempted to enroll in the program and whether they were successful. Of the 333 women contacted by phone to assess enrollment efforts, 21% had a high likelihood of limited literacy (a score of 0–1 on the Newest Vital Sign assessment), 48% had a chance of limited literacy (a score of 2–3), and 31% had adequate literacy (a score of 4–6). Attempting to self-enroll was not associated with health literacy (p = .70), but successful enrollment was more likely with higher literacy (p = .01). Results suggested a positive association between health literacy skills and successful self-enrollment in the Text4Baby program, which suggests the need for additional outreach efforts to assure enrollment by women with low health literacy skills.

Calcium intake and mortality from all causes, cancer, and cardiovascular disease: the Cancer Prevention Study II Nutrition Cohort

BACKGROUND Calcium intake may be important for bone health, but its effects on other outcomes, including cardiovascular disease (CVD) and cancer, remain unclear. Recent reports of adverse cardiovascular effects of supplemental calcium have raised concerns. OBJECTIVE We investigated associations of supplemental, dietary, and total calcium intakes with all-cause, CVD-specific, and cancer-specific mortality in a large, prospective cohort. DESIGN A total of 132,823 participants in the Cancer Prevention Study II Nutrition Cohort, who were followed from baseline (1992 or 1993) through 2012 for mortality outcomes, were included in the analysis. Dietary and supplemental calcium information was first collected at baseline and updated in 1999 and 2003. Multivariable-adjusted Cox proportional hazards models with cumulative updating of exposures were used to calculate RRs and 95% CIs for associations between calcium intake and mortality. RESULTS During a mean follow-up of 17.5 y, 43,186 deaths occurred. For men, supplemental calcium intake was overall not associated with mortality outcomes (P-trend > 0.05 for all), but men who were taking ≥1000 mg supplemental calcium/d had a higher risk of all-cause mortality (RR: 1.17; 95% CI: 1.03, 1.33), which was primarily attributed to borderline statistically significant higher risk of CVD-specific mortality (RR: 1.22; 95% CI: 0.99, 1.51). For women, supplemental calcium was inversely associated with mortality from all causes [RR (95% CI): 0.90 (0.87, 0.94), 0.84 (0.80, 0.88), and 0.93 (0.87, 0.99) for intakes of 0.1 to <500, 500 to <1000, and ≥1000 mg/d, respectively; P-trend < 0.01]. Total calcium intake was inversely associated with mortality in women (P-trend < 0.01) but not in men; dietary calcium was not associated with all-cause mortality in either sex. CONCLUSIONS In this cohort, associations of calcium intake and mortality varied by sex. For women, total and supplemental calcium intakes are associated with lower mortality, whereas for men, supplemental calcium intake ≥1000 mg/d may be associated with higher all-cause and CVD-specific mortality.

Obesity, diabetes, serum glucose, and risk of primary liver cancer by birth cohort, race/ethnicity, and sex: Multiphasic health checkup study

OBJECTIVE Obesity and diabetes have been associated with liver cancer. However, recent US-based studies have suggested a lack of association between obesity and liver cancer among blacks and women. METHODS We conducted a nested case-control study within the Multiphasic Health Checkup (MHC) cohort of Kaiser Permanente Northern California (KPNC) members. Liver cancer was diagnosed using the KPNC Cancer Registry. Detailed self-administered questionnaires and a standardized examination that included measurement of height and weight and a 1-h glucose tolerance test were completed prior to diagnosis of liver cancer for cases (n=450) and matched controls (4489). Height and weight were utilized to calculate BMI (kg/m(2)) as a measure of adiposity: underweight (15-≤8.5kg/m(2)), normal weight (18.5-≤25kg/m(2)), overweight (25-≤30kg/m(2)), and obese (≥30kg/m(2)). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between BMI, diabetes, and serum glucose with subsequent incidence of liver cancer, in models that were stratified by birth cohort, race/ethnicity, and sex. RESULTS Compared to normal weight individuals, obese individuals had a 2.4-fold increased risk of liver cancer (OR=2.38, 95% CI: 1.68-3.36), and overweight individuals had a 32% increased risk (OR=1.32, 95% CI: 1.03-1.70). This association did not differ when stratified by birth cohort, race/ethnicity, or sex (pint>0.05). Among blacks and women, obesity was associated with at least a 2-fold increased risk of liver cancer (OR=2.29, 95% CI: 1.22-4.28 and OR=2.00, 95% CI: 1.14-3.52, respectively). More moderate increased odds ratios were noted for diabetes (OR=1.28, 95% CI: 0.65-2.54) and serum glucose ≥200mg/dL (OR=1.63, 95% CI: 0.48-5.55), although the results did not attain statistical significance. CONCLUSION In summary, our finding of a positive association between obesity and liver cancer suggests that a higher BMI may increase the risk of liver cancer in the US, for both sexes and all race/ethnicities.

Associations of antibiotic use with risk of primary liver cancer in the Clinical Practice Research Datalink

Background:Use of antibiotics could alter human microbiota composition and decrease bacterial diversity. Such microbial dysbiosis may have implications in hepatocarcinogenesis; however, the association between antibiotic use and liver cancer risk has been minimally examined in humans.Methods:We performed a nested case–control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom’s Clinical Practice Research Datalink. Antibiotic use was obtained from prescription records. Multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using conditional logistic regression.Results:Ever-use of prescription antibiotics was associated with a slightly increased risk of liver cancer, compared to non-use (OR=1.22, 95% CI=1.03−1.45). However, there was no clear dose–response relationship by the number of prescriptions or cumulative dose of antibiotic use, suggesting a non-causal association.Conclusions:Our results do not support a role of antibiotic use in liver cancer development.

Adiposity across the adult life course and incidence of primary liver cancer: The NIH‐AARP cohort

Obesity relatively late in adulthood has been consistently associated with increased risk of primary liver cancer. However, little is known about the role of early adult adiposity and evolution of adiposity across adulthood in hepatocarcinogenesis. We examined adult body mass index (BMI; kg/m2) in relation to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a large prospective cohort. Weight at ages 18, 35, 50 and at study baseline was retrospectively reported by 303,620 participants. BMI trajectories were identified using latent class trajectory modeling. Incidence of HCC and ICC was determined through 2011. Cox proportional hazards modeling was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 372 HCC cases and 104 ICC cases occurred during follow‐up. Being obese (BMI ≥ 30) at ages 18, 35, 50 and at baseline (mean age 62.3 years, range 50.3–71.5 years) was associated with an 86–119% elevated risk of HCC. BMI trajectories that resulted in obesity were associated with ∼80% higher HCC incidence. BMI at age 18, per 5 kg/m2, was associated with a 34% higher risk of ICC, but the association attenuated for BMI at older ages. In conclusion, our findings suggest that maintaining a healthy BMI throughout the lifetime may reduce liver cancer risk. Future studies with longitudinally collected weight information are warranted to further elucidate the role of life‐course adiposity in liver cancer development.

Circulating Biomarkers of Gut Barrier Function: Correlates and Nonresponse to Calcium Supplementation among Colon Adenoma Patients

Background: Gut barrier dysfunction contributes to several gastrointestinal disorders, including colorectal cancer, but factors associated with intestinal hyperpermeability have been minimally studied in humans. Methods: We tested the effects of two doses of calcium (1.0 or 2.0 g/d) on circulating biomarkers of gut permeability [anti-flagellin and anti-lipopolysaccharide (LPS) Ig, measured via ELISA] over a 4-month treatment period among colorectal adenoma patients in a randomized, double-blinded, placebo-controlled clinical trial (n = 193), and evaluated the factors associated with baseline levels of these biomarkers. Results: Baseline concentrations of anti-flagellin IgA and anti-LPS IgA were, respectively, statistically significantly proportionately higher by 11.8% and 14.1% among men, 31.3% and 39.8% among those with a body mass index ≥ 35 kg/m2, and 19.9% and 22.0% among those in the upper relative to the lowest sex-specific tertile of waist circumference. A combined permeability score (the summed optical densities of all four biomarkers) was 24.3% higher among women in the upper tertile of plasma C–reactive protein (Ptrend < 0.01). We found no appreciable effects of supplemental calcium on anti-flagellin or anti-LPS Igs. Conclusions: Our results suggest that (i) men and those with higher adiposity may have greater gut permeability, (ii) gut permeability and systemic inflammation may be directly associated with one another, and (iii) supplemental calcium may not modify circulating levels of gut permeability biomarkers within 4 months. Impact: Our findings may improve the understanding of the factors that influence gut permeability to inform development of treatable biomarkers of risk for colorectal cancer and other health outcomes. Cancer Epidemiol Biomarkers Prev; 25(2); 318–26. ©2015 AACR.

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based study in SEER-Medicare

Objectives Intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinomas are rare tumors that arise from the epithelial cells of the bile ducts, and the etiology of both cancer types is poorly understood. Thus, we utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare resource to examine risk factors and novel preexisting medical conditions that may be associated with these cancer types. Methods Between 2000 and 2011, 2,092 ICC and 2,981 ECC cases and 323,615 controls were identified using the SEER-Medicare database. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results Non-alcoholic fatty liver disease was associated with approximately 3-fold increased risks of ICC (OR = 3.52, 95% CI: 2.87–4.32) and ECC (OR = 2.93, 95% CI: 2.42–3.55). Other metabolic conditions, including obesity and type 2 diabetes, were also associated with increased risks of both cancer types. Smoking was associated with a 46% and 77% increased ICC and ECC risk, respectively. Several autoimmune/inflammatory conditions, including type 1 diabetes and gout, were associated with increased risks of ICC/ECC. As anticipated, viral hepatitis, alcohol-related disorders, and bile duct conditions were associated with both cancer types. However, thyrotoxicosis and hemochromatosis were associated with an increased risk of ICC but not ECC, but did not remain significantly associated after Bonferroni correction. Conclusions In this study, risk factors for ICC and ECC were similar, with the exceptions of thyrotoxicosis and hemochromatosis. Notably, metabolic conditions were associated with both cancer types. As metabolic conditions are increasing in prevalence, these could be increasingly important risk factors for both types of cholangiocarcinoma.

Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States.

Background Telomere shortening is an important molecular event in hepatocellular carcinoma (HCC) initiation; however, its role in HCC progression and prognosis is less clear. Our study aimed to examine the association of telomere length with survival of patients with HCC. Methods We measured telomere length in tumor and adjacent non-tumor tissues from 126 persons with HCC in the United States (U.S.) who were followed for mortality outcomes. Relative telomere length (RTL) was measured by a monochrome multiplex quantitative polymerase chain reaction assay. Multivariable Cox proportional hazards modeling was used to calculate hazard ratios (HRs) and 95% CIs for the association between telomere length and all-cause mortality. We also examined associations between telomere length and patient characteristics using multiple linear regression. Results During a mean follow-up of 6.0 years, 79 deaths occurred among 114 individuals for whom survival data were available. The ratio of RTL in tumor relative to non-tumor tissue was greater for individuals with regional or distant stage tumors (0.97) than localized stage tumors (0.77), and for individuals with grade III or IV tumors (0.95) than grade II (0.88) or grade I (0.67) tumors. An RTL ratio ≥1 was not associated with survival (HR 0.92, 95% CI 0.55, 1.55) compared to a ratio <1, after adjusting for age at diagnosis, sex, tumor stage and tumor size. Similarly, RTL in the tumor and non-tumor tissue, respectively, were not associated with survival. Conclusions This U.S. based study found that telomeres may be longer in more aggressive HCCs. There was no evidence, however, that telomere length was associated with survival of patients with HCC. Future investigations are warranted to clarify the role of telomere length in HCC prognosis.