Imperial College London

Professor Amanda Cross

Faculty of MedicineSchool of Public Health

Professor of Cancer Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3338amanda.cross

 
 
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Assistant

 

Mr Will Kay +44 (0)20 7594 3350

 
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Location

 

Room 1089Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

325 results found

Jiao L, Stolzenberg-Solomon R, Zimmerman TP, Duan Z, Chen L, Kahle L, Risch A, Subar AF, Cross AJ, Hollenbeck A, Vlassara H, Striker G, Sinha Ret al., 2015, Dietary consumption of advanced glycation end products and pancreatic cancer in the prospective NIH-AARP Diet and Health Study, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 101, Pages: 126-134, ISSN: 0002-9165

Journal article

Cross AJ, Moore SC, Boca S, Huang W-Y, Xiong X, Stolzenberg-Solomon R, Sinha R, Sampson JNet al., 2014, A Prospective Study of Serum Metabolites and Colorectal Cancer Risk, CANCER, Vol: 120, Pages: 3049-3057, ISSN: 0008-543X

Journal article

Cross AJ, Major JM, Rothman N, Sinha Ret al., 2014, Urinary 1-methylhistidine and 3-methylhistidine, meat intake, and colorectal adenoma risk., Eur J Cancer Prev, Vol: 23, Pages: 385-390

Self-reported red and processed meat intake has been positively associated with colorectal adenoma and cancer; however, measurement error in self-reported data can attenuate risk estimates, increasing the need for improved exposure assessment methods to better understand this association. A controlled feeding study revealed that urinary 1-methylhistidine and 3-methylhistidine levels were dose-dependently associated with meat intake; our aim was to examine these analytes in relation to colorectal adenoma. Individuals undergoing routine cancer screening by sigmoidoscopy or colonoscopy were recruited for a colorectal adenoma case-control study; participants completed a food frequency questionnaire and a meat questionnaire, and donated urine. Urinary 1-methylhistidine and 3-methylhistidine levels were measured in 131 case-control pairs (age, sex, and smoking matched); odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Although the mean self-reported red meat intake was higher in cases (59 g/day) than in controls (48 g/day), the mean urinary 1-methylhistidine and 3-methylhistidine levels did not differ by case status (P=0.72). Neither urinary 1-methylhistidine nor urinary 3-methylhistidine was associated with colorectal adenoma (OR continuous=0.90, 95% CI: 0.53-1.54; OR continuous=0.90, 95% CI: 0.69-1.17, respectively). A variable combining self-reported red meat intake with urinary 1-methylhistidine and 3-methylhistidine levels was not associated with colorectal adenoma. Analyzing urine samples from multiple days from 17 individuals revealed intraclass correlations of 0.52 and 0.49 for 1-methylhistidine and 3-methylhistidine, respectively; this variability could result in attenuated risks. Urinary 1-methylhistidine and 3-methylhistidine levels, measured in one sample, were not associated with colorectal adenoma.

Journal article

Erdman JW, Jeffery E, Hendrickx M, Cross AJ, Lampe JWet al., 2014, Can Food Processing Enhance Cancer Protection?, Nutr Today, Vol: 49, Pages: 230-234, ISSN: 0029-666X

Journal article

Dik VK, Murphy N, Siersema PD, Fedirko V, Jenab M, Kong SY, Hansen CP, Overvad K, Tjonneland A, Olsen A, Dossus L, Racine A, Bastide N, Li K, Kuehn T, Boeing H, Aleksandrova K, Trichopoulou A, Trichopoulos D, Barbitsioti A, Palli D, Contiero P, Vineis P, Tumino R, Panico S, Peeters PHM, Weiderpass E, Skeie G, Hjartaker A, Amiano P, Sanchez M-J, Fonseca-Nunes A, Barricarte A, Chirlaque M-D, Redondo M-L, Jirstrom K, Manjer J, Nilsson LM, Wennberg M, Bradbury KE, Khaw K-T, Wareham N, Cross AJ, Riboli E, Bueno-de-Mesquita HBet al., 2014, Prediagnostic Intake of Dairy Products and Dietary Calcium and Colorectal Cancer Survival-Results from the EPIC Cohort Study, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 23, Pages: 1813-1823, ISSN: 1055-9965

Journal article

Cross AJ, Boca S, Freedman ND, Caporaso NE, Huang W-Y, Sinha R, Sampson JN, Moore SCet al., 2014, Metabolites of tobacco smoking and colorectal cancer risk., Carcinogenesis, Vol: 35, Pages: 1516-1522

Colorectal cancer is not strictly considered a tobacco-related malignancy, but modest associations have emerged from large meta-analyses. Most studies, however, use self-reported data, which are subject to misclassification. Biomarkers of tobacco exposure may reduce misclassification and provide insight into metabolic variability that potentially influences carcinogenesis. Our aim was to identify metabolites that represent smoking habits and individual variation in tobacco metabolism, and investigate their association with colorectal cancer. In a nested case-control study of 255 colorectal cancers and 254 matched controls identified in the Prostate, Lung, Colorectal and Ovarian cancer screening trial, baseline serum was used to identify metabolites by ultra-high-performance liquid-phase chromatography and mass spectrometry, as well as gas chromatography with tandem mass spectrometry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Self-reported current smoking was associated with serum cotinine, O-cresol sulfate and hydroxycotinine. Self-reported current smoking of any tobacco (OR = 1.90, 95% CI: 1.02-3.54) and current cigarette smoking (OR = 1.51, 95% CI: 0.75-3.04) were associated with elevated colorectal cancer risks, although the latter was not statistically significant. Individuals with detectable levels of hydroxycotinine had an increased colorectal cancer risk compared with those with undetectable levels (OR = 2.68, 95% CI: 1.33-5.40). Although those with detectable levels of cotinine had a suggestive elevated risk of this malignancy (OR = 1.81, 95% CI: 0.98-3.33), those with detectable levels of O-cresol sulfate did not (OR = 1.16, 95% CI: 0.57-2.37). Biomarkers capturing smoking behavior and metabolic variation exhibit stronger associations with colorectal cancer than self-report, providing additional evidence for a role for tobacco in this malignancy.

Journal article

Guertin KA, Moore SC, Sampson JN, Huang W-Y, Xiao Q, Stolzenberg-Solomon RZ, Sinha R, Cross AJet al., 2014, Metabolomics in nutritional epidemiology: identifying metabolites associated with diet and quantifying their potential to uncover diet-disease relations in populations., Am J Clin Nutr, Vol: 100, Pages: 208-217

BACKGROUND: Metabolomics is an emerging field with the potential to advance nutritional epidemiology; however, it has not yet been applied to large cohort studies. OBJECTIVES: Our first aim was to identify metabolites that are biomarkers of usual dietary intake. Second, among serum metabolites correlated with diet, we evaluated metabolite reproducibility and required sample sizes to determine the potential for metabolomics in epidemiologic studies. DESIGN: Baseline serum from 502 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was analyzed by using ultra-high-performance liquid-phase chromatography with tandem mass spectrometry and gas chromatography-mass spectrometry. Usual intakes of 36 dietary groups were estimated by using a food-frequency questionnaire. Dietary biomarkers were identified by using partial Pearson's correlations with Bonferroni correction for multiple comparisons. Intraclass correlation coefficients (ICCs) between samples collected 1 y apart in a subset of 30 individuals were calculated to evaluate intraindividual metabolite variability. RESULTS: We detected 412 known metabolites. Citrus, green vegetables, red meat, shellfish, fish, peanuts, rice, butter, coffee, beer, liquor, total alcohol, and multivitamins were each correlated with at least one metabolite (P < 1.093 × 10(-6); r = -0.312 to 0.398); in total, 39 dietary biomarkers were identified. Some correlations (citrus intake with stachydrine) replicated previous studies; others, such as peanuts and tryptophan betaine, were novel findings. Other strong associations included coffee (with trigonelline-N-methylnicotinate and quinate) and alcohol (with ethyl glucuronide). Intraindividual variability in metabolite levels (1-y ICCs) ranged from 0.27 to 0.89. Large, but attainable, sample sizes are required to detect associations between metabolites and disease in epidemiologic studies, further emphasizing the usefulness of metabolomics in nutritio

Journal article

Abid Z, Cross AJ, Sinha R, 2014, Meat, dairy, and cancer., Am J Clin Nutr, Vol: 100 Suppl 1, Pages: 386S-393S

In 2007 the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) report judged that the evidence for an association between red and processed meat consumption and colorectal cancer was convincing. In addition, the effect of other animal products on cancer risk has been studied, and the WCRF/AICR report concluded that milk probably decreases the risk of colorectal cancer but diets high in calcium probably increase the risk of prostate cancer, whereas there was limited evidence for an association between milk and bladder cancer and insufficient evidence for other cancers. There are several potential mechanisms relating meat to cancer, including heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and heme iron. Although the evidence in favor of a link between red and processed meat and colorectal cancer is convincing, the relations with other cancers are unclear. In this review, we summarize cohort studies conducted by the National Cancer Institute on meat and dairy intake in relation to cancer since the 2007 WCRF/AICR report. We also report the findings of meta-analyses published since 2007.

Journal article

Robertson DJ, Lieberman DA, Winawer SJ, Ahnen DJ, Baron JA, Schatzkin A, Cross AJ, Zauber AG, Church TR, Lance P, Greenberg ER, Martínez MEet al., 2014, Colorectal cancers soon after colonoscopy: a pooled multicohort analysis., Gut, Vol: 63, Pages: 949-956

OBJECTIVE: Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps. DESIGN: Primary data were pooled from eight large (>800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection. RESULTS: 9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection. CONCLUSIONS: Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy.

Journal article

Xiao Q, Moore SC, Boca SM, Matthews CE, Rothman N, Stolzenberg-Solomon RZ, Sinha R, Cross AJ, Sampson JNet al., 2014, Sources of Variability in Metabolite Measurements from Urinary Samples, PLOS ONE, Vol: 9, ISSN: 1932-6203

Journal article

Moore SC, Matthews CE, Sampson JN, Stolzenberg-Solomon RZ, Zheng W, Cai Q, Tan YT, Chow W-H, Ji B-T, Liu DK, Xiao Q, Boca SM, Leitzmann MF, Yang G, Xiang YB, Sinha R, Shu XO, Cross AJet al., 2014, Human metabolic correlates of body mass index., Metabolomics, Vol: 10, Pages: 259-269, ISSN: 1573-3882

BACKGROUND: A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role. DESIGN: In order to discover novel metabolic biomarkers of BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 participants and examined the cross-sectional associations between metabolite levels and BMI. Participants were from three studies in the United States and China. Height, weight, and potential confounders were ascertained by questionnaire (US studies) or direct measurement (Chinese study). Metabolite levels were measured using liquid-phase chromatography and gas chromatography coupled with mass spectrometry. We evaluated study-specific associations using linear regression, adjusted for age, gender, and smoking, and we estimated combined associations using random effects meta-analysis. RESULTS: The meta-analysis revealed 37 metabolites significantly associated with BMI, including 19 lipids, 12 amino acids, and 6 others, at the Bonferroni significance threshold (p<0.00016). Eighteen of these associations had not been previously reported, including histidine, an amino acid neurotransmitter, and butyrylcarnitine, a lipid marker of whole-body fatty acid oxidation. Heterogeneity by study was minimal (all Pheterogeneity >0.05). In total, 110 metabolites were associated with BMI at the p<0.05 level. CONCLUSION: These findings establish a baseline for the BMI metabolome, and suggest new targets for researchers attempting to clarify mechanistic links between high BMIs and disease risk.

Journal article

Ruder EH, Berndt SI, Gilsing AMJ, Graubard BI, Burdett L, Hayes RB, Weissfeld JL, Ferrucci LM, Sinha R, Cross AJet al., 2014, Dietary iron, iron homeostatic gene polymorphisms and the risk of advanced colorectal adenoma and cancer., Carcinogenesis, Vol: 35, Pages: 1276-1283

Dietary iron intake and variation in iron homeostasis genes may affect colorectal neoplasia risk. We conducted two nested case-control studies within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: one of advanced colorectal adenoma (1205 cases; 1387 controls) and one of colorectal cancer (370 cases; 401 controls). Iron intake was estimated with a food frequency questionnaire and genotyping was performed for 21 genes. Unconditional logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (95% CIs) for colorectal neoplasia risk within quartiles of intake. Several single nucleotide polymorphisms (SNPs) modified the association between iron intake and the risk of adenoma or cancer. Dietary iron was positively associated with colorectal adenoma among three SNPs of HEPHL1, including carriers of the AA genotype at rs7946162 (ORQ4-Q1 = 2.22, 95% CI 1.15-4.27, Ptrend = 0.03; Pinteraction = 0.10), the TT genotype at rs2460063 (ORQ4-Q1 = 2.39, 95% CI 1.26-4.54, Ptrend = 0.02; Pinteraction = 0.04) and the GG genotype at rs7127348 (ORQ4-Q1 = 2.40, 95% CI 1.23-4.67, Ptrend = 0.02; Pinteraction = 0.09). Heme iron was positively associated with colorectal cancer among those with GG genotypes for ACO1 rs10970985 (ORQ4-Q 1 = 2.45, 95% CI 3.40-8.06, Ptrend = 0.004; Pinteraction = 0.05). However, none of the associations were statistically significant after adjustment for multiple comparisons. Future studies should target the specific genes and SNPs for which the association was significant prior to multiple comparison correction.

Journal article

Boca SM, Sinha R, Cross AJ, Moore SC, Sampson JNet al., 2014, Testing multiple biological mediators simultaneously., Bioinformatics, Vol: 30, Pages: 214-220

MOTIVATION: Modern biomedical and epidemiological studies often measure hundreds or thousands of biomarkers, such as gene expression or metabolite levels. Although there is an extensive statistical literature on adjusting for 'multiple comparisons' when testing whether these biomarkers are directly associated with a disease, testing whether they are biological mediators between a known risk factor and a disease requires a more complex null hypothesis, thus offering additional methodological challenges. RESULTS: We propose a permutation approach that tests multiple putative mediators and controls the family wise error rate. We demonstrate that, unlike when testing direct associations, replacing the Bonferroni correction with a permutation approach that focuses on the maximum of the test statistics can significantly improve the power to detect mediators even when all biomarkers are independent. Through simulations, we show the power of our method is 2-5× larger than the power achieved by Bonferroni correction. Finally, we apply our permutation test to a case-control study of dietary risk factors and colorectal adenoma to show that, of 149 test metabolites, docosahexaenoate is a possible mediator between fish consumption and decreased colorectal adenoma risk. AVAILABILITY AND IMPLEMENTATION: R-package included in online Supplementary Material.

Journal article

Ashmore JH, Lesko SM, Miller PE, Cross AJ, Muscat JE, Zhu J, Liao J, Harper G, Lazarus P, Hartman TJet al., 2013, Association of dietary and supplemental iron and colorectal cancer in a population-based study., Eur J Cancer Prev, Vol: 22, Pages: 506-511

We evaluated the role of dietary iron, heme iron, and supplemental iron on colorectal cancer (CRC) risk in a population-based case-control study in Pennsylvania, including 1005 incident cases and 1062 controls. Diet was assessed through a modified food frequency questionnaire that included supplement use and a meat-specific module. Cases reported intakes for the year before diagnosis, whereas controls reported intakes for the year before interview. Heme iron intake was calculated using a new heme database developed by the US National Cancer Institute. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. After multivariate adjustment, there were no significant associations between heme iron or total iron intake and CRC incidence. Dietary iron intake was inversely associated with CRC among women (OR Q5 vs. Q1=0.45; 95% CI=0.22-0.92), but not among men. Supplemental iron intake of more than 18 mg/day versus none was positively associated with CRC incidence (OR=2.31; 95% CI=1.48-3.59; P-trend<0.001), an effect that was observed in both men (OR=2.56; 95% CI=1.30-5.05) and women (OR=2.46; 95% CI=1.34-4.52). These findings suggest that consumption of more than 18 mg/day of supplemental iron may increase risk for CRC.

Journal article

Miller PE, Cross AJ, Subar AF, Krebs-Smith SM, Park Y, Powell-Wiley T, Hollenbeck A, Reedy Jet al., 2013, Comparison of 4 established DASH diet indexes: examining associations of index scores and colorectal cancer., Am J Clin Nutr, Vol: 98, Pages: 794-803

BACKGROUND: Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge. OBJECTIVE: We compared 4 established DASH indexes and examined associations with colorectal cancer. DESIGN: Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Günther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models. RESULTS: From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Günther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Günther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). CONCLUSION: The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results.

Journal article

Cross AJ, Hollenbeck AR, Park Y, 2013, A large prospective study of risk factors for adenocarcinomas and malignant carcinoid tumors of the small intestine., Cancer Causes Control, Vol: 24, Pages: 1737-1746

PURPOSE: Small intestinal cancer is increasing in the U.S.A, yet little is known about its etiology. Our aim was to prospectively evaluate risk factors for this malignancy by the two main histologic subtypes (adenocarcinomas and carcinoids). METHODS: Hazard ratios and 95% confidence intervals (CI) were estimated for all incident small intestinal cancers (n = 237), adenocarcinomas (n = 84), and malignant carcinoids (n = 124), by demographic and lifestyle factors among 498,376 men and women. RESULTS: Age was the only risk factor for adenocarcinomas (HR for ≥ 65 vs. 50-55 years = 3.12, 95% CI 1.33, 7.31). Age (HR for ≥ 65 vs. 50-55 years = 3.31, 95% CI 1.51, 7.28), male sex (HR = 1.44, 95% CI 1.01, 2.05), body mass index (BMI, HR for ≥ 35 vs. 18.5-< 25 kg/m2 = 1.95, 95% CI 1.06, 3.58), and current menopausal hormone therapy use (HR = 1.94, 95% CI 1.07, 3.50) were positively associated with malignant carcinoids. A family history of any cancer or colorectal cancer (HR = 1.42, 95% CI 0.99, 2.03; 1.61, 0.97, 2.65, respectively), or a personal history of colorectal polyps (HR = 1.51, 95% CI 0.92, 2.46) produced elevated, but not statistically significant, risks for malignant carcinoids. Race, education, diabetes, smoking, physical activity, and alcohol intake were not associated with either histologic subtype. CONCLUSIONS: Risk factors differed according to cancer subtype; only age was associated with adenocarcinomas, whereas age, male sex, BMI, and menopausal hormone therapy use were positively associated with malignant carcinoids.

Journal article

Cross AJ, Lampe JW, Rock CL, 2013, Biomarkers and their use in nutrition intervention, Pages: 209-225

Journal article

Arem H, Gunter MJ, Cross AJ, Hollenbeck AR, Sinha Ret al., 2013, A prospective investigation of fish, meat and cooking-related carcinogens with endometrial cancer incidence, BRITISH JOURNAL OF CANCER, Vol: 109, Pages: 756-760, ISSN: 0007-0920

Journal article

Keimling M, Renehan AG, Behrens G, Fischer B, Hollenbeck AR, Cross AJ, Leitzmann MFet al., 2013, Comparison of associations of body mass index, abdominal adiposity, and risk of colorectal cancer in a large prospective cohort study., Cancer Epidemiol Biomarkers Prev, Vol: 22, Pages: 1383-1394

BACKGROUND: Increased body mass index (BMI) is an established colorectal cancer risk factor. High waist circumference or waist-hip-ratio (WHR) may better reflect an abnormal metabolic state and be more predictive of colorectal cancer risk than BMI. METHODS: We examined BMI, waist circumference, WHR, and hip circumference in relation to colorectal cancer risk among 203,177 participants followed for 10 years. We derived standardized colorectal cancer risk estimates for each anthropometric parameter and compared predictive characteristics (Harrell's C-index). In women, we examined whether hormone replacement therapy (HRT) use modified the associations between anthropometric measures and colorectal cancer. RESULTS: We ascertained 2,869 colorectal cancers. In men, increased colon cancer risks were associated with BMI [HR per SD, 1.14; 95% confidence interval (CI), 1.08-1.20], waist circumference (HR per SD, 1.17; 95% CI, 1.08-1.27), and WHR (HR per SD, 1.09; 95% CI, 1.04-1.14). In women, anthropometric variables were unrelated to colon cancer. For men and women, anthropometric variables were unrelated to rectal cancer. Compared with BMI, waist circumference and WHR did not materially influence colon cancer prediction models [C-index changes: -0.0041 and 0.0046 (men); 0.0004 and 0.0005 (women)]. In current HRT users, colon cancer was inversely or suggestively inversely associated with waist circumference (HR per SD, 0.78; 95% CI, 0.63-0.97) and WHR (HR per SD, 0.88; 95% CI, 0.76-1.01), but positively related to hip circumference (HR per SD, 1.39; 95% CI, 1.13-1.71). CONCLUSION: BMI, waist circumference, and WHR show comparable positive associations with colon cancer in men. Associations between anthropometric measures and colon cancer are weak or null in women, but there is some evidence for effect modification by HRT. IMPACT: These findings may improve our understanding of the relation of adiposity to colorectal cancer.

Journal article

Sampson JN, Boca SM, Shu XO, Stolzenberg-Solomon RZ, Matthews CE, Hsing AW, Tan YT, Ji B-T, Chow W-H, Cai Q, Liu DK, Yang G, Xiang YB, Zheng W, Sinha R, Cross AJ, Moore SCet al., 2013, Metabolomics in epidemiology: sources of variability in metabolite measurements and implications., Cancer Epidemiol Biomarkers Prev, Vol: 22, Pages: 631-640

BACKGROUND: Metabolite levels within an individual vary over time. This within-individual variability, coupled with technical variability, reduces the power for epidemiologic studies to detect associations with disease. Here, the authors assess the variability of a large subset of metabolites and evaluate the implications for epidemiologic studies. METHODS: Using liquid chromatography/mass spectrometry (LC/MS) and gas chromatography-mass spectroscopy (GC/MS) platforms, 385 metabolites were measured in 60 women at baseline and year-one of the Shanghai Physical Activity Study, and observed patterns were confirmed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening study. RESULTS: Although the authors found high technical reliability (median intraclass correlation = 0.8), reliability over time within an individual was low. Taken together, variability in the assay and variability within the individual accounted for the majority of variability for 64% of metabolites. Given this, a metabolite would need, on average, a relative risk of 3 (comparing upper and lower quartiles of "usual" levels) or 2 (comparing quartiles of observed levels) to be detected in 38%, 74%, and 97% of studies including 500, 1,000, and 5,000 individuals. Age, gender, and fasting status factors, which are often of less interest in epidemiologic studies, were associated with 30%, 67%, and 34% of metabolites, respectively, but the associations were weak and explained only a small proportion of the total metabolite variability. CONCLUSION: Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiologic studies. IMPACT: We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology.

Journal article

Laiyemo AO, Doubeni C, Brim H, Ashktorab H, Schoen RE, Gupta S, Charabaty A, Lanza E, Smoot DT, Platz E, Cross AJet al., 2013, Short- and long-term risk of colorectal adenoma recurrence among whites and blacks., Gastrointest Endosc, Vol: 77, Pages: 447-454

BACKGROUND: It is unclear whether the higher burden from colorectal cancer among blacks is due to an increased biological susceptibility. OBJECTIVE: To determine whether non-Hispanic blacks (blacks) have a higher risk of adenoma recurrence than non-Hispanic whites (whites) after removal of colorectal adenoma. DESIGN: Secondary analysis of the Polyp Prevention Trial (PPT) data. SETTING: United States. PATIENTS: Patients were 1668 self-identified whites and 153 blacks who completed the 4-year trial. Of these, 688 whites and 55 blacks enrolled in a posttrial, passive Polyp Prevention Trial Continued Follow-up Study (PPT-CFS) and underwent another colonoscopy. MAIN OUTCOME MEASUREMENTS: Recurrence and location of the adenoma and advanced adenoma by race-ethnicity during PPT and cumulative recurrence over a mean follow-up of 8.3 years (range, 4.9-12.4 years) among PPT-CFS enrollees. RESULTS: Blacks had similar risk of recurrence of adenoma (39.2% vs 39.4%; incidence risk ratio [RR] = .98; 95% CI, .80-1.20) and advanced adenoma (8.5% vs 6.4%; RR = 1.18; 95% CI, .68-2.05) as whites at the end of PPT. Recurrence risk did not differ by colon subsite. Among PPT-CFS enrollees, the cumulative recurrence rate over a maximal follow-up period of 12 years was similar for blacks and whites for adenoma (67.3% vs 67.0%; RR = 1.01; 95% CI, .84-1.21) and advanced adenoma (14.5% vs 16.9%; RR = 1.03; 95% CI, .60-1.79). LIMITATION: There were few blacks in the long-term follow-up study. CONCLUSIONS: Adenoma and advanced adenoma recurrence did not differ by race. Our study does not support more frequent surveillance colonoscopies for blacks with a personal history of adenoma as an intervention to reduce colorectal cancer disparity.

Journal article

Dellavalle CT, Daniel CR, Aschebrook-Kilfoy B, Hollenbeck AR, Cross AJ, Sinha R, Ward MHet al., 2013, Dietary intake of nitrate and nitrite and risk of renal cell carcinoma in the NIH-AARP Diet and Health Study., Br J Cancer, Vol: 108, Pages: 205-212

BACKGROUND: Nitrate and nitrite are present in many foods and are precursors of N-nitroso compounds, known animal carcinogens and potential human carcinogens. We prospectively investigated the association between nitrate and nitrite intake from dietary sources and risk of renal cell carcinoma (RCC) overall and clear cell and papillary histological subtypes in the NIH-AARP Diet and Health Study. METHODS: Nitrate and nitrite intakes were estimated from a 124-item food frequency questionnaire. Over a mean follow-up of 9 years, we identified 1816 RCC cases (n=498, clear cell; n=115, papillary cell) among 491 841 participants. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Individuals in the highest quintile of nitrite intake from animal sources compared with those in the lowest quintile, had an increased risk of total RCC and clear cell subtype (HR=1.28, 95% CI, 1.10-1.49 and HR=1.68, 95% CI, 1.25-2.27, respectively). Nitrite from processed meats and other animal sources were associated with increased clear cell adenocarcinoma risk (HR=1.33, 95% CI, 1.01-1.76 and HR=1.78, 95% CI, 1.34-2.36, respectively). We found no association for nitrite intake from plant sources or nitrate intake overall. CONCLUSION: Our findings suggest that nitrite from animal sources may increase the risk of RCC, particularly clear cell adenocarcinomas.

Journal article

Cross AJ, Bobe G, Young M, Lanza E, Colburn Net al., 2013, Chemoprotective Effects of Kaempferol in Colorectal Tumorigenesis, Kaempferol: Chemistry, Natural Occurrences and Health Benefits, Editors: Villers, Fougere, Publisher: Nova Science Publishers, New York, US

Book chapter

Cross AJ, Lampe JW, Rock CJ, 2013, Biomarkers and their use in nutrition intervention, Nutrition in the prevention and treatment of disease, Editors: Coulston, Boushey, Ferruzzi, Publisher: Oxford, UK: Elsevier

Book chapter

Laiyemo AO, Doubeni C, Pinsky PF, Doria-Rose VP, Marcus PM, Schoen RE, Lanza E, Cross AJet al., 2013, Factors associated with the risk of adenoma recurrence in distal and proximal colon., Digestion, Vol: 87, Pages: 141-146

BACKGROUND/AIMS: Colonoscopy may be less effective in preventing cancer in the proximal colon. We evaluated whether risk factors for adenoma recurrence exhibit differential effect on adenoma recurrence by colon subsite. METHODS: We examined the association of age, sex, body mass index, smoking status and use of nonsteroidal anti-inflammatory drugs (NSAIDs) on proximal and distal adenoma recurrence among 1,864 participants in the Polyp Prevention Trial. We used multinomial logistic regression models to calculate the relative risk ratios (RRR) and 95% CI. RESULTS: 733 (39.3%) participants had adenoma recurrence (228 distal only, 369 proximal only and 136 synchronous proximal and distal adenoma). When compared to participants without adenoma recurrence, no factor was associated with an increased risk of distal only adenoma recurrence. Age 65-69 years (RRR = 1.47, 95% CI 1.00-2.16), age ≥70 years (RRR = 2.24, 95% CI 1.57-3.20), and male sex (RRR = 1.73, 95% CI 1.32-2.27) were positively associated with proximal only adenoma recurrence. NSAIDs use was associated with a reduced risk of adenoma recurrence by similar magnitude in distal (RRR = 0.78, 95% CI 0.58-1.07) and proximal colon (RRR = 0.77, 95% CI 0.60-1.00). CONCLUSIONS: We did not find any modifiable risk factor that differentially increases proximal as compared to distal adenoma recurrence to be clinically useful for targeted intervention.

Journal article

Miller PE, Lazarus P, Lesko SM, Cross AJ, Sinha R, Laio J, Zhu J, Harper G, Muscat JE, Hartman TJet al., 2013, Meat-related compounds and colorectal cancer risk by anatomical subsite., Nutr Cancer, Vol: 65, Pages: 202-226

Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends < 0.05). For analyses by meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends < 0.05). Inverse associations were observed between unprocessed poultry and colorectal, colon, proximal colon, and rectal tumors; grilled/barbequed poultry and proximal colon cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends < 0.05). HCAs, PAHs, nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted.

Journal article

Martinez ME, Thompson P, Messer K, Ashbeck EL, Lieberman DA, Baron JA, Ahnen DJ, Robertson DJ, Jacobs ET, Greenberg ER, Cross AJ, Atkin Wet al., 2012, One-year risk for advanced colorectal neoplasia: U.S. versus U.K. Risk-stratification guidelines., Ann Intern Med, Vol: 157, Pages: 856-864

Journal article

Renehan AG, Flood A, Adams KF, Olden M, Hollenbeck AR, Cross AJ, Leitzmann MFet al., 2012, Body mass index at different adult ages, weight change, and colorectal cancer risk in the National Institutes of Health-AARP Cohort., Am J Epidemiol, Vol: 176, Pages: 1130-1140

The authors investigated the relations of body mass index at different ages and adult weight change to incident colorectal cancer risk in the prospective National Institutes of Health-AARP Diet and Health Study (1995-1996), using a subcohort with repeated recall weights (273,679 participants; mean baseline age = 62.8 years). During 2,509,662 person-years follow-up, 4076 incident colorectal cancers were ascertained. For men, an increased risk of colon cancer but not rectal cancer was associated with body mass index at baseline age (per 5-kg/m(2) increase, hazard ratio (HR) = 1.18, 95% confidence interval (CI): 1.11, 1.25), at age 50 years (HR = 1.18, 95% CI: 1.10, 1.26), and at age 35 years (HR = 1.16, 95% CI: 1.07, 1.25) but less so at age 18 years. Weight gained between the ages of 18 and 35 years and between 18 years of age and the baseline age was associated with an increased risk of colon cancer in men (per 0.5-kg/year increase, HR = 1.18, 95% CI: 1.11, 1.25 and HR = 1.29, 95% CI: 1.16, 1.56, respectively). For women, relations throughout were weaker than those observed for men. These findings suggest that weight gains during early to middle adulthood have important influences on colon cancer risk, especially in men.

Journal article

Cook MB, Kamangar F, Weinstein SJ, Albanes D, Virtamo J, Taylor PR, Abnet CC, Wood RJ, Petty G, Cross AJ, Dawsey SMet al., 2012, Iron in relation to gastric cancer in the Alpha-tocopherol, Beta-carotene Cancer Prevention Study., Cancer Epidemiol Biomarkers Prev, Vol: 21, Pages: 2033-2042

BACKGROUND: Iron is an essential micronutrient that can have carcinogenic effects when at high or low concentrations. Previous studies of iron in relation to gastric cancer have not assessed subtype-specific relationships. We used the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to assess whether iron metrics were associated with gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). METHODS: We selected 341 incident gastric cancer cases (86 cardia, 172 noncardia, and 83 nonspecified), accrued during 22 years of follow-up, and 341 individually matched controls. We measured prediagnostic serum iron, ferritin, unsaturated iron binding capacity, and C-reactive protein. Total iron-binding capacity (TIBC) and transferrin saturation were estimated from these metrics. Dietary iron exposures were estimated from a food frequency questionnaire. Multivariable logistic regression was used for analysis. RESULTS: Serum iron metrics were not associated with GCC, except for a potential "n"-shaped relationship with TIBC (global P = 0.038). GNCC was inversely associated with serum ferritin (global P = 0.024), serum iron (global P = 0.060) and, possibly, transferrin saturation. TIBC appeared to share a "u"-shaped relationship with GNCC (global P = 0.033). Dietary iron exposures were not associated with either subsite. Adjustment for Helicobacter pylori and gastric atrophy had little effect on observed associations. CONCLUSIONS: We found little evidence for the involvement of iron exposure in the pathogenesis of GCC. GNCC was associated with an iron profile similar to that of iron deficiency. IMPACT: Our findings indicate that inverse associations between iron metrics and gastric cancer are driven by associations with GNCC. Further elucidation of potential mechanisms is warranted.

Journal article

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