Erikka Loftfield

Association of Coffee Consumption With Overall and Cause-Specific Mortality in a Large US Prospective Cohort Study

Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998-2001) or history of cardiovascular disease at study enrollment (1993-2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (<1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2-3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4-5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); ≥6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression.

Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study

PURPOSE Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers. METHODS One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2) were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months. RESULTS The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m(2), and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05). CONCLUSION Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care.

Coffee Drinking and Cutaneous Melanoma Risk in the NIH-AARP Diet and Health Study

BACKGROUND Cutaneous melanoma is the fifth most common cancer in the United States. Modifiable risk factors, with the exception of exposure to ultraviolet radiation (UVR), are poorly understood. Coffee contains numerous bioactive compounds and may be associated inversely with melanoma. However, previous epidemiological evidence is limited. METHODS Coffee intake was assessed at baseline with a food frequency questionnaire in the National Institutes of Health-AARP prospective cohort study. Among 447 357 non-Hispanic whites who were cancer-free at baseline, 2904 incident cases of malignant melanoma were identified during 4 329 044 person-years of follow-up, with a median of 10.5 years of follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee intake and subsequent melanoma risk with non-coffee drinkers as the reference group. Statistical tests were two-sided, and P values less than .05 were interpreted as statistically significant. RESULTS The highest category of coffee intake was inversely associated with malignant melanoma (≥4 cups/day: HR = 0.80, 95% CI = 0.68 to 0.93, P trend = .01). This association was statistically significant for caffeinated (≥4 cups/day: HR = 0.75, 95% CI = 0.64 to 0.89, P trend = .01) but not for decaffeinated coffee (P trend = .55). CONCLUSIONS Higher coffee intake was associated with a modest decrease in risk of melanoma in this large US cohort study. Additional investigations of coffee intake and its constituents, particularly caffeine, with melanoma are warranted.

Associations of Coffee Drinking with Systemic Immune and Inflammatory Markers

Background: Coffee drinking has been inversely associated with mortality as well as cancers of the endometrium, colon, skin, prostate, and liver. Improved insulin sensitivity and reduced inflammation are among the hypothesized mechanisms by which coffee drinking may affect cancer risk; however, associations between coffee drinking and systemic levels of immune and inflammatory markers have not been well characterized. Methods: We used Luminex bead-based assays to measure serum levels of 77 immune and inflammatory markers in 1,728 older non-Hispanic Whites. Usual coffee intake was self-reported using a food frequency questionnaire. We used weighted multivariable logistic regression models to examine associations between coffee and dichotomized marker levels. We conducted statistical trend tests by modeling the median value of each coffee category and applied a 20% false discovery rate criterion to P values. Results: Ten of the 77 markers were nominally associated (P trend < 0.05) with coffee drinking. Five markers withstood correction for multiple comparisons and included aspects of the host response namely chemotaxis of monocytes/macrophages (IFNγ, CX3CL1/fractalkine, CCL4/MIP-1β), proinflammatory cytokines (sTNFRII), and regulators of cell growth (FGF-2). Heavy coffee drinkers had lower circulating levels of IFNγ [odds ratios (OR), 0.35; 95% confidence intervals (CI), 0.16–0.75], CX3CL1/fractalkine (OR, 0.25; 95% CI, 0.10–0.64), CCL4/MIP-1β (OR, 0.48; 95% CI, 0.24–0.99), FGF-2 (OR, 0.62; 95% CI, 0.28–1.38), and sTNFRII (OR, 0.34; 95% CI, 0.15–0.79) than non-coffee drinkers. Conclusions: Lower circulating levels of inflammatory markers among coffee drinkers may partially mediate previously observed associations of coffee with cancer and other chronic diseases. Impact: Validation studies, ideally controlled feeding trials, are needed to confirm these associations. Cancer Epidemiol Biomarkers Prev; 24(7); 1052–60. ©2015 AACR.

Coffee Drinking Is Widespread in the United States, but Usual Intake Varies by Key Demographic and Lifestyle Factors

BACKGROUND Despite widespread popularity and possible health effects, the prevalence and distribution of coffee consumption in US adults are poorly characterized. OBJECTIVE We sought to estimate usual daily coffee intakes from all coffee-containing beverages, including decaffeinated and regular coffee, among US adults according to demographic, socioeconomic, and health-related factors. METHODS Dietary intake data from ≤2 nonconsecutive 24-h dietary recalls and a food-frequency questionnaire administered during the NHANES 2003-2006 were used to estimate the person-specific probability of consuming coffee on a particular day and the usual amount consumed on consumption days. Trends in population mean coffee consumption over time were evaluated by using multiple linear regression and 1-d 24-h recall data from NHANES 2003-2012. Analyses were weighted to be representative of the US adult population aged ≥20 y. RESULTS An estimated 154 million adults, or 75% of the US population, aged ≥20 y reported drinking coffee; 49% reported drinking coffee daily. Prevalence did not vary by sex, education, income, or self-reported general health (all P ≥ 0.05) but did vary by age, race/ethnicity, smoking status, and alcohol drinking (all P < 0.05). Among coffee drinkers, the mean ± SE usual intake was 14.1 ± 0.5 fluid ounces/d (417 ± 15 mL/d). Mean usual intakes were higher in men than women, in older age groups than in those aged 20 to <30 y, in non-Hispanic whites than in non-Hispanic blacks or Hispanic/other races, in smokers than in never smokers, and in daily alcohol consumers than in nonconsumers (all P < 0.05). Population mean coffee consumption was stable from 2003 to 2012 (P-trend = 0.09). CONCLUSIONS Coffee is widely consumed in the United States, with usual intakes varying by lifestyle and demographic factors, most notably by age. Longitudinal studies are needed to determine whether observed differences by age reflect birth cohort effects or changes in drinking patterns over the lifetime.

Coffee consumption and incidence of lung cancer in the NIH-AARP Diet and Health Study

BACKGROUND Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee drinkers tend to also be cigarette smokers, such findings could be confounded. Therefore, we examined this association in the nearly half a million participants of the US NIH-AARP Diet and Health Study. METHODS Typical coffee intake and smoking history were queried at baseline. During 4 155 256 person-years of follow-up, more than 9000 incident lung cancer cases occurred. We used Cox proportional hazards regression to estimate hazard ratios (HRs)and 95% confidence intervals for coffee intake and subsequent incidence of lung cancer. We also comprehensively adjusted for tobacco smoking and examined associations by detailed strata of tobacco use. RESULTS Coffee drinkers were far more likely to smoke than non-drinkers. Although coffee drinking was associated with lung cancer in age- and sex- adjusted models (HR for ≥ 6 cups/day compared with none: 4.56, 4.08-5.10), this association was substantially attenuated after adjusting for smoking (HR: 1.27, 1.14-1.42). Similar findings were observed for each different histological type of lung cancer, and for participants drinking predominantly caffeinated or decaffeinated coffee. Little evidence for an association was observed in our stratified analyses, either within never smokers or in most categories of tobacco use. CONCLUSIONS Coffee drinking was positively associated with lung cancer in our study, although the association was substantially attenuated after adjustment for tobacco smoking. As our adjustment for lifetime tobacco use was imperfect, it is likely that the remaining association is due to residual confounding by smoking, although other explanations are possible.

Comparison of Collection Methods for Fecal Samples for Discovery Metabolomics in Epidemiologic Studies

Background: The gut metabolome may be associated with the incidence and progression of numerous diseases. The composition of the gut metabolome can be captured by measuring metabolite levels in the feces. However, there are little data describing the effect of fecal sample collection methods on metabolomic measures. Methods: We collected fecal samples from 18 volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT). One set of samples was frozen after collection (day 0), and for 95% ethanol, FOBT, and FIT, a second set was frozen after 96 hours at room temperature. We evaluated (i) technical reproducibility within sample replicates, (ii) stability after 96 hours at room temperature for 95% ethanol, FOBT, and FIT, and (iii) concordance of metabolite measures with the putative “gold standard,” day 0 samples without solution. Results: Intraclass correlation coefficients (ICC) estimating technical reproducibility were high for replicate samples for each collection method. ICCs estimating stability at room temperature were high for 95% ethanol and FOBT (median ICC > 0.87) but not FIT (median ICC = 0.52). Similarly, Spearman correlation coefficients (rs) estimating metabolite concordance with the “gold standard” were higher for 95% ethanol (median rs = 0.82) and FOBT (median rs = 0.70) than for FIT (median rs = 0.40). Conclusions: Metabolomic measurements appear reproducible and stable in fecal samples collected with 95% ethanol or FOBT. Concordance with the “gold standard” is highest with 95% ethanol and acceptable with FOBT. Impact: Future epidemiologic studies should collect feces using 95% ethanol or FOBT if interested in studying fecal metabolomics. Cancer Epidemiol Biomarkers Prev; 25(11); 1483–90. ©2016 AACR.

Contemporary impact of tobacco use on periodontal disease in the USA

Periodontal disease (PD) is a common chronic disease that can be expensive to treat, and when untreated, can inflict significant morbidity and tooth loss. Growing evidence also links PD to higher risks of cancer, cardiovascular and other chronic diseases. Cigarette smoking has been estimated to cause 8 million cases of PD in the USA or more than half of the 15 million cases of PD.1 However, these estimates are based on data from the third National Health and Nutrition Examination Survey (NHANES), conducted from 1988 to 1994. The prevalence of PD was underestimated in this survey because a partial mouth examination was utilised that included many fewer sites per tooth than currently recommended.2 Current prevalence estimates of PD in the USA are substantially higher, as they incorporate new population-based PD case definitions and full-mouth assessments.3 Equally important, previous estimates of the tobacco-induced PD burden failed to include the effects of non-cigarette tobacco products and environmental tobacco smoke (ETS). There have also …

Association between Regular Aspirin Use and Circulating Markers of Inflammation: A Study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Background: Regular aspirin use may decrease cancer risk by reducing chronic inflammation. However, associations between aspirin use and circulating markers of inflammation have not been well studied. Methods: Serum levels of 78 inflammatory markers were measured in 1,819 55- to 74-year-old men and women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Data were combined from three completed case–control studies and reweighted to the PLCO screening arm. Self-reported aspirin and ibuprofen use (number of tablets taken per day/week/month) over the previous 12 months was collected at baseline. Associations between (i) nonregular (<4 tablets/month), (ii) low (1–4 tablets/week), (iii) moderate (1 tablet/day), or (iv) high (2+ tablets/day) regular aspirin or ibuprofen use and marker levels were assessed with weighted logistic regression. Results: Aspirin use was nominally associated with (Ptrend across categories ≤ 0.05) decreased levels of chemokine C-C motif ligand 15 [CCL15; OR, 0.5; 95% confidence intervals (CI), 0.3–0.8; moderate versus nonregular use]; soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 0.7; 95% CI, 0.4–1.0); soluble tumor necrosis factor receptor 1 (sTNFR1; OR, 0.6; 95% CI, 0.4–0.9) and increased levels of CCL13 (OR, 1.3; 95% CI, 0.8–2.1); CCL17 (OR, 1.1; 95% CI, 0.7–1.9) and interleukin 4 (IL4; OR, 1.6; 95% CI, 0.9–2.8). Trends were not statistically significant following correction for multiple comparisons. Likewise, no statistically significant associations were observed between ibuprofen use and marker levels. Conclusions: No significant associations were observed between regular aspirin use and the inflammatory markers assessed. Impact: Additional studies are needed to better understand the relationship between aspirin use, chronic inflammation, and cancer risk. Cancer Epidemiol Biomarkers Prev; 24(5); 825–32. ©2015 AACR.

Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and VIRAHEP-C Trials

More than 150 million people worldwide are chronically infected with hepatitis C virus (HCV) and face higher risk of cirrhosis and hepatocellular carcinoma. Highly effective HCV treatments have recently been developed; however, they are costly and therefore poorly suited for application in resource-limited settings where HCV burden is high. Pegylated-interferon alpha (PEG-IFNα) and ribavirin (RBV) therapy is far less costly, but also less effective. Vitamin D supplementation has been proposed as an inexpensive adjuvant to treatment, however, prior epidemiological evidence on its effectiveness is inconsistent, with little data available among African Americans who naturally have lower vitamin D concentrations. We thus evaluated associations between baseline vitamin D status, measured by circulating 25-hydroxyvitamin D (25(OH)D), which is considered to be the best marker of vitamin D status in humans, and subsequent response to PEG-IFNα/RBV therapy in two large clinical trials that together included 1292 patients infected with HCV genotype 1. We used race-stratified logistic regression models to evaluate multivariable-adjusted associations of 25(OH)D with early virologic response (EVR; 2-log10 HCV RNA decline at week 12) and sustained virologic response (SVR). Among African Americans, we saw no associations. Among European Americans, we saw no association with low vitamin D (≤20 ng/mL) versus sufficient concentrations (20-<30 ng/mL). However, patients with 25(OH)D ≥30 ng/mL were actually less likely to attain EVR (OR = 0.64, 95% CI = 0.43–0.94) than those with sufficient concentrations, with a similar but non-significant association observed for SVR (OR = 0.49, 95% CI = 0.20–1.17). Conclusion Higher vitamin D status was not beneficially associated with responses to therapy; if anything, patients with higher vitamin D concentrations were less likely to attain SVR. Our data do not support a role for vitamin D supplementation as an adjuvant therapy for HCV.