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

Laiyemo AO, Doubeni C, Badurdeen DS, Murphy G, Marcus PM, Schoen RE, Lanza E, Smoot DT, Cross AJet al., 2012, Obesity, weight change, and risk of adenoma recurrence: a prospective trial, ENDOSCOPY, Vol: 44, ISSN: 0013-726X

Journal article

Laiyemo AO, Doubeni C, Badurdeen DS, Murphy G, Marcus PM, Schoen RE, Lanza E, Smoot DT, Cross AJet al., 2012, Obesity, weight change, and risk of adenoma recurrence: a prospective trial, ENDOSCOPY, Vol: 44, Pages: 813-818, ISSN: 0013-726X

Journal article

Sinha R, Cross AJ, Daniel CR, Graubard BI, Wu JW, Hollenbeck AR, Gunter MJ, Park Y, Freedman NDet al., 2012, Caffeinated and decaffeinated coffee and tea intakes and risk of colorectal cancer in a large prospective study, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 96, Pages: 374-381, ISSN: 0002-9165

Journal article

Cross AJ, Harnly JM, Ferrucci LM, Risch A, Mayne ST, Sinha Ret al., 2012, Developing a heme iron database for meats according to meat type, cooking method and doneness level., Food Nutr Sci, Vol: 3, Pages: 905-913, ISSN: 2157-944X

BACKGROUND: Animal studies have demonstrated that iron may be related to carcinogenesis, and human studies found that heme iron can increase the formation of N-nitroso compounds, which are known carcinogens. OBJECTIVES: One of the postulated mechanisms linking red meat intake to cancer risk involves iron. Epidemiologic studies attempt to investigate the association between heme iron intake and cancer by applying a standard factor to total iron from meat. However, laboratory studies suggest that heme iron levels in meat vary according to cooking method and doneness level. We measured heme iron in meats cooked by different cooking methods to a range of doneness levels to use in conjunction with a food frequency questionnaire to estimate heme iron intake. METHODS: Composite meat samples were made to represent each meat type, cooking method and doneness level. Heme iron was measured using atomic absorption spectrometry and inductively coupled plasma-atomic emission spectrometry. RESULTS: Steak and hamburgers contained the highest levels of heme iron, pork and chicken thigh meat had slightly lower levels, and chicken breast meat had the lowest. CONCLUSIONS: Although heme iron levels varied, there was no clear effect of cooking method or doneness level. We outline the methods used to create a heme iron database to be used in conjunction with food frequency questionnaires to estimate heme iron intake in relation to disease outcome.

Journal article

Gilsing AMJ, Berndt SI, Ruder EH, Graubard BI, Ferrucci LM, Burdett L, Weissfeld JL, Cross AJ, Sinha Ret al., 2012, Meat-related mutagen exposure, xenobiotic metabolizing gene polymorphisms and the risk of advanced colorectal adenoma and cancer., Carcinogenesis, Vol: 33, Pages: 1332-1339

Meat mutagens, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs), may be involved in colorectal carcinogenesis depending on their activation or detoxification by phase I and II xenobiotic metabolizing enzymes (XME). Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we examined the intake of five meat mutagens and >300 single nucleotide polymorphisms (SNPs) in 18 XME genes in relation to advanced colorectal adenoma (1205 cases and 1387 controls) and colorectal cancer (370 cases and 401 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake of meat mutagens was assessed using a food frequency questionnaire with a detailed meat-cooking module. An interaction was observed between 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake and the NAT1 polymorphism rs6586714 in the adenoma study (P(interaction) = 0.001). Among individuals carrying a GG genotype, high MeIQx intake was associated with a 43% increased risk of adenoma (95% CI 1.11-1.85, P(trend) = 0.07), whereas the reverse was observed among carriers of the A variant (OR = 0.50, 95% CI 0.30-0.84, P(trend) = 0.01). In addition, we observed some suggestive (P < 0.05) modifying effects for SNPs in other XME genes (UGT1A, CYP2E1, EPHX1, AHR and GSTM3), but these were not significant after adjustment for multiple testing. This large and comprehensive study of XME genes, meat mutagens and the risk of colorectal tumours found that a NAT1 polymorphism modified the association between MeIQx intake and colorectal adenoma risk.

Journal article

Daniel CR, Sinha R, Park Y, Graubard BI, Hollenbeck AR, Morton LM, Cross AJet al., 2012, Meat intake is not associated with risk of non-Hodgkin lymphoma in a large prospective cohort of U.S. men and women., J Nutr, Vol: 142, Pages: 1074-1080

Meat intake has been inconsistently associated with risk of non-Hodgkin lymphoma (NHL), a heterogeneous group of malignancies of the lymphoid tissue etiologically linked to immunomodulatory factors. In a large U.S. cohort, we prospectively investigated several biologically plausible mechanisms related to meat intake, including meat-cooking and meat-processing compounds, in relation to NHL risk by histologic subtype. At baseline (1995-1996), participants of the NIH-AARP Diet and Health Study completed a diet and lifestyle questionnaire (n = 492,186), and a subcohort (n = 302,162) also completed a questionnaire on meat-cooking methods and doneness levels. Over a mean of 9 y of follow-up, we identified 3611 incident cases of NHL. In multivariable Cox proportional hazards regression models, we found no association between intake of red meat, processed meat, fish, poultry, heme iron, nitrite, nitrate, animal fat, or protein and NHL risk. MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), heterocyclic amines formed in meats cooked to well done at high temperatures, were inversely associated with chronic lymphocytic leukemia/small lymphocytic lymphoma [n = 979; HR (95% CI) for the highest vs. lowest quintile of intake: 0.73 (0.55, 0.96) and 0.77 (0.61, 0.98), respectively]. In this large U.S. cohort, meat intake was not associated with NHL or any histologic subtypes of NHL. Contrary to findings in animal models and other cancer sites, meat-cooking and -processing compounds did not increase NHL risk.

Journal article

Wu JW, Cross AJ, Baris D, Ward MH, Karagas MR, Johnson A, Schwenn M, Cherala S, Colt JS, Cantor KP, Rothman N, Silverman DT, Sinha Ret al., 2012, Dietary intake of meat, fruits, vegetables, and selective micronutrients and risk of bladder cancer in the New England region of the United States., Br J Cancer, Vol: 106, Pages: 1891-1898

BACKGROUND: Despite many studies on diet and bladder cancer, there are areas that remain unexplored including meat mutagens, specific vegetable groups, and vitamins from diet. METHODS: We conducted a population-based case-control study of bladder cancer in Maine, New Hampshire, and Vermont. A total of 1171 cases were ascertained through hospital pathology records and cancer registries from 2001 to 2004. Overall, 1418 controls were identified from the Department of Motor Vehicles (<65 years) and Center for Medicaid and Medicare Services (65-79 years) and were frequency-matched to cases by state, sex, and age (within 5 years). Diet was assessed with a self-administered Diet History Questionnaire. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Processed meat intake was positively associated with bladder cancer (highest vs lowest quartile OR: 1.28; 95% CI: 1.00-1.65; P(trend)=0.035), with a stronger association for processed red meat (OR: 1.41; 95% CI: 1.08-1.84; P(trend)=0.024). There were no associations between intake of fruits or vegetables and bladder cancer. We did, however, observe an inverse association with vitamin B12 intake (OR: 0.77; 95% CI: 0.61-0.99; P=0.019). CONCLUSION: Vitamin B12 from diet may be protective against bladder cancer, whereas consuming processed meat may increase risk.

Journal article

Bobe G, Murphy G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, Cross AJet al., 2012, Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial, INTERNATIONAL JOURNAL OF CANCER, Vol: 130, Pages: 1649-1659, ISSN: 0020-7136

Journal article

Ward MH, Cross AJ, Abnet CC, Sinha R, Markin RS, Weisenburger DDet al., 2012, Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach., Eur J Cancer Prev, Vol: 21, Pages: 134-138

Iron can cause oxidative stress and DNA damage, and heme iron can catalyze endogenous formation of N-nitroso compounds, which are potent carcinogens. Dietary iron promotes esophageal cancer incidence in animal studies and has been identified as a growth factor for Helicobacter pylori, an established risk factor for stomach cancer. We conducted a population-based case-control study of adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in Nebraska. Heme iron and total iron intake were estimated from a food frequency questionnaire and databases of heme and total iron. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for known risk factors. Esophageal cancer was positively associated with higher intakes of heme iron (ORQ4 vs. Q1=3.04, 95% CI: 1.20-7.72; P trend=0.009) and total iron from meat sources (ORQ4 vs. Q1=2.67, 95% CI: 0.99-7.16; P trend=0.050). Risk of stomach cancer was elevated among those with higher intakes of heme iron (ORQ4 vs.Q1=1.99, 95% CI: 1.00-3.95; P trend=0.17) and total iron from meat (OR=2.26, 95% CI: 1.14-4.46; P trend=0.11). Iron intake from all dietary sources was not significantly associated with risk of either cancer. Our results suggest that high intakes of heme and iron from meat may be important dietary risk factors for esophageal and stomach cancer and may partly explain associations with red meat.

Journal article

Brown DA, Hance KW, Rogers CJ, Sansbury LB, Albert PS, Murphy G, Laiyemo AO, Wang Z, Cross AJ, Schatzkin A, Danta M, Srasuebkul P, Amin J, Law M, Breit SN, Lanza Eet al., 2012, Serum Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15): A Potential Screening Tool for the Prevention of Colon Cancer?, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 21, Pages: 337-346, ISSN: 1055-9965

Journal article

Ferrucci LM, Sinha R, Huang W-Y, Berndt SI, Katki HA, Schoen RE, Hayes RB, Cross AJet al., 2012, Meat consumption and the risk of incident distal colon and rectal adenoma., Br J Cancer, Vol: 106, Pages: 608-616

BACKGROUND: Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis. METHODS: Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17,072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression. RESULTS: We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04-2.36), well or very well-done meat (OR=1.59, 95% CI=1.05-2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17-2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06-2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03-2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56-0.86) and iron from supplements (OR=0.65, 95% CI=0.44-0.97) were inversely associated with any distal colorectal adenoma. CONCLUSION: Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma.

Journal article

Tasevska N, Jiao L, Cross AJ, Kipnis V, Subar AF, Hollenbeck A, Schatzkin A, Potischman Net al., 2012, Sugars in diet and risk of cancer in the NIH-AARP Diet and Health Study., Int J Cancer, Vol: 130, Pages: 159-169

Prospective epidemiologic data on the effects of different types of dietary sugars on cancer incidence have been limited. In this report, we investigated the association of total sugars, sucrose, fructose, added sugars, added sucrose and added fructose in the diet with risk of 24 malignancies. Participants (n = 435,674) aged 50-71 years from the NIH-AARP Diet and Health Study were followed for 7.2 years. The intake of individual sugars was assessed using a 124-item food frequency questionnaire (FFQ). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) in multivariable models adjusted for confounding factors pertinent to individual cancers. We identified 29,099 cancer cases in men and 13,355 cases in women. In gender-combined analyses, added sugars were positively associated with risk of esophageal adenocarcinoma (HR(Q5 vs. Q1) : 1.62, 95% CI: 1.07-2.45; p(trend) = 0.01), added fructose was associated with risk of small intestine cancer (HR(Q5 vs. Q1) : 2.20, 95% CI: 1.16-4.16; p(trend) = 0.009) and all investigated sugars were associated with increased risk of pleural cancer. In women, all investigated sugars were inversely associated with ovarian cancer. We found no association between dietary sugars and risk of colorectal or any other major cancer. Measurement error in FFQ-reported dietary sugars may have limited our ability to obtain more conclusive findings. Statistically significant associations observed for the rare cancers are of interest and warrant further investigation.

Journal article

Cross AJ, Lampe JW, Rock CL, 2012, Biomarkers and Their Use in Nutrition Intervention, Nutrition in the Prevention and Treatment of Disease, Third Edition, Pages: 209-225, ISBN: 9780123918840

Book chapter

Daniel CR, Cross AJ, Graubard BI, Park Y, Ward MH, Rothman N, Hollenbeck AR, Chow W-H, Sinha Ret al., 2012, Large prospective investigation of meat intake, related mutagens, and risk of renal cell carcinoma., Am J Clin Nutr, Vol: 95, Pages: 155-162

BACKGROUND: The evidence for meat intake and renal cell carcinoma (RCC) risk is inconsistent. Mutagens related to meat cooking and processing, and variation by RCC subtype may be important to consider. OBJECTIVE: In a large US cohort, we prospectively investigated intake of meat and meat-related compounds in relation to risk of RCC, as well as clear cell and papillary RCC histologic subtypes. DESIGN: Study participants (492,186) completed a detailed dietary assessment linked to a database of heme iron, heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAHs), nitrate, and nitrite concentrations in cooked and processed meats. Over 9 (mean) y of follow-up, we identified 1814 cases of RCC (498 clear cell and 115 papillary adenocarcinomas). HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. RESULTS: Red meat intake [62.7 g (quintile 5) compared with 9.8 g (quintile 1) per 1000 kcal (median)] was associated with a tendency toward an increased risk of RCC [HR: 1.19; 95% CI: 1.01, 1.40; P-trend = 0.06] and a 2-fold increased risk of papillary RCC [P-trend = 0.002]. Intakes of benzo(a)pyrene (BaP), a marker of PAHs, and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), an HCA, were associated with a significant 20-30% elevated risk of RCC and a 2-fold increased risk of papillary RCC. No associations were observed for the clear cell subtype. CONCLUSIONS: Red meat intake may increase the risk of RCC through mechanisms related to the cooking compounds BaP and PhIP. Our findings for RCC appeared to be driven by strong associations with the rarer papillary histologic variant. This study is registered at clinicaltrials.gov as NCT00340015.

Journal article

Aschebrook-Kilfoy B, Ward MH, Gierach GL, Schatzkin A, Hollenbeck AR, Sinha R, Cross AJet al., 2012, Epithelial ovarian cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study., Eur J Cancer Prev, Vol: 21, Pages: 65-72

Ovarian cancer is a leading cause of cancer death among women in the United States and it has the highest mortality rate of all gynecologic cancers. Internationally, there is a five-fold variation in incidence and mortality of ovarian cancer, which suggests a role for environmental factors, including diet. Nitrate and nitrite are found in various food items and they are precursors of N-nitroso compounds, which are known carcinogens in animal models. We evaluated dietary nitrate and nitrite intake and epithelial ovarian cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study, including 151 316 women aged 50-71 years at the time of the baseline questionnaire in 1995-1996. The nitrate and nitrite intake was assessed using a 124-item validated food frequency questionnaire. Through 31 December 2006, 709 incident epithelial ovarian cancer cases with complete dietary information were identified. Using Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs), women in the highest intake quintile of dietary nitrate had a 31% increased risk (95% CI: 1.01-1.68) of epithelial ovarian cancer, compared with those in the lowest intake quintile. Although there was no association for total dietary nitrite, those in the highest intake category of animal sources of nitrite had a 34% increased risk (95% CI: 1.05-1.69) of ovarian cancer. There were no clear differences in risk by histologic subtype of ovarian cancer. Our findings suggest that a role of dietary nitrate and nitrite in ovarian cancer risk should be followed in other large cohort studies.

Journal article

Major JM, Cross AJ, Watters JL, Hollenbeck AR, Graubard BI, Sinha Ret al., 2011, Patterns of meat intake and risk of prostate cancer among African-Americans in a large prospective study., Cancer Causes Control, Vol: 22, Pages: 1691-1698

OBJECTIVE: Given the large racial differences in prostate cancer risk, further investigation of diet and prostate cancer is warranted among high-risk groups. The purpose of this study was to examine the association between type of meat intake and prostate cancer risk among African-American men. METHODS: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995-1996) data from African-American participants, aged 50-71 years. Incident prostate cancer cases (n = 1,089) were identified through 2006. Dietary and risk factor data were ascertained by questionnaires administered at baseline. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) within intake quantiles. RESULTS: Neither white nor processed meat intake was associated with prostate cancer, regardless of meat-cooking method. Red meats cooked at high temperatures were associated with an increased risk of prostate cancer (HR = 1.18, 95% CI = 1.00-1.38 and HR = 1.22, 95% CI = 1.03-1.44, for the upper two intake tertiles). Intake of the heterocyclic amine (HCA), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (DiMeIQx) was positively associated with prostate cancer (HR = 1.30; 95% CI = 1.05-1.61, p = 0.02). No associations were observed for intake of other HCAs. CONCLUSION: Red meats cooked at high temperatures were positively associated with prostate cancer risk among African-American men. Further studies are needed to replicate these findings.

Journal article

Ruder EH, ThiƩbaut ACM, Thompson FE, Potischman N, Subar AF, Park Y, Graubard BI, Hollenbeck AR, Cross AJet al., 2011, Adolescent and mid-life diet: risk of colorectal cancer in the NIH-AARP Diet and Health Study., Am J Clin Nutr, Vol: 94, Pages: 1607-1619

BACKGROUND: Colorectal cancer has a natural history of several decades; therefore, the diet consumed decades before diagnosis may aid in understanding this malignancy. OBJECTIVE: The objective was to investigate diet during adolescence and 10 y before baseline (ages 40-61 y) in relation to colorectal cancer. DESIGN: Participants in the NIH-AARP Diet and Health Study (n = 292,797) completed a 124-item food-frequency questionnaire (FFQ) about diet in the past 12 mo and two 37-item FFQs about diet at ages 12-13 y and 10 y previously. Cox regression was used to estimate multivariate HRs and 95% CIs for colon (n = 2794) and rectal (n = 979) cancers within quintiles of exposures. RESULTS: Colon cancer risk was lower in the highest than in the lowest quintile of vitamin A (HR: 0.82; 95% CI: 0.72, 0.92) and vegetable (HR: 0.81, 0.70, 0.92) intakes during adolescence. Those in the highest intake category 10 y previously for calcium (HR: 0.83; 95% CI: 0.73, 0.94), vitamin A (HR: 0.81; 95% CI: 0.71, 0.92), vitamin C (HR: 0.83; 95% CI: 0.72, 0.95), fruit (HR: 0.84; 95% CI: 0.73, 0.97), and milk (HR: 0.78; 95% CI: 0.67, 0.90) had a lower risk of colon cancer, but a higher risk was observed for total fat (HR: 1.15; 95% CI: 1.01, 1.30), red meat (HR: 1.31; 95% CI: 1.12, 1.53), and processed meat (HR: 1.24; 95% CI: 1.06, 1.45). For rectal cancer, milk was inversely associated (HR: 0.75; 95% CI: 0.58, 0.96) with risk. CONCLUSION: Adolescent and midlife diet may play a role in colorectal carcinogenesis.

Journal article

Major JM, Cross AJ, Doubeni CA, Park Y, Lian M, Hollenbeck AR, Schatzkin A, Graubard BI, Sinha Ret al., 2011, Socioeconomic deprivation impact on meat intake and mortality: NIH-AARP Diet and Health Study., Cancer Causes Control, Vol: 22, Pages: 1699-1707

OBJECTIVE: Previous studies have not examined potential interactions between meat intake and characteristics of the local environment on the risk of mortality. This study examined the impact of area socioeconomic deprivation on the association between meat intake and all-cause and cause-specific mortality after accounting for individual-level risk factors. METHODS: In the prospective NIH-AARP Diet and Health Study, we analyzed data from adults, ages 50-71 years at baseline (1995-1996). Individual-level dietary intake and health risk information were linked to the demographic and socioeconomic context of participants' local environment based on census tract data. Deaths (n = 33,831) were identified through December 2005. Multilevel Cox models were used to estimate hazard ratios and 95% confidence intervals for quintiles of area deprivation scores. RESULTS: Associations of red and processed meats with mortality were consistent across deprivation quintiles. Men residing in least-deprived neighborhoods had a stronger protective effect for white meat consumption. No differences by deprivation index were observed for women. CONCLUSION: Red and processed meat intake increases mortality risk regardless of level of deprivation within a given neighborhood suggesting biological mechanisms rather than neighborhood contextual factors may underlie these meat-mortality associations. The effect of white meat intake on cancer mortality was modified by area deprivation among men.

Journal article

Daniel CR, Cross AJ, Graubard BI, Hollenbeck AR, Park Y, Sinha Ret al., 2011, Prospective investigation of poultry and fish intake in relation to cancer risk., Cancer Prev Res (Phila), Vol: 4, Pages: 1903-1911

Dietary guidelines advise consumers to limit intake of red meat and choose lean protein sources, such as poultry and fish. Poultry consumption has been steadily increasing in the United States, but the effect on cancer risk remains unclear. In a large U.S. cohort, we prospectively investigated poultry and fish intake and cancer risk across a range of malignancies in men and women. Diet was assessed at baseline (1995-1996) with a food frequency questionnaire in 492,186 participants of the NIH-AARP Diet and Health Study. Over a mean follow-up of 9 years, we identified 74,418 incident cancer cases. In multivariable Cox proportional hazards regression models, we estimated the substitution and addition effects of white meat (poultry and fish) intake in relation to cancer risk. In substitution models with total meat intake held constant, a 10-g (per 1,000 kcal) increase in white meat intake offset by an equal decrease in red meat intake was associated with a statistically significant reduced (3%-20%) risk of cancers of the esophagus, liver, colon, rectum, anus, lung, and pleura. In addition models with red meat intake held constant, poultry intake remained inversely associated with esophageal squamous cell carcinoma, liver cancer, and lung cancer, but we observed mixed findings for fish intake. As the dietary recommendations intend, the inverse association observed between white meat intake and cancer risk may be largely due to the substitution of red meat. Simply increasing fish or poultry intake, without reducing red meat intake, may be less beneficial for cancer prevention.

Journal article

Lam TK, Cross AJ, Freedman N, Park Y, Hollenbeck AR, Schatzkin A, Abnet Cet al., 2011, Dietary fiber and grain consumption in relation to head and neck cancer in the NIH-AARP Diet and Health Study., Cancer Causes Control, Vol: 22, Pages: 1405-1414

BACKGROUND: Dietary fiber and grain consumption may reduce the risk of head and neck cancer; however, the epidemiological evidence is limited. We investigated this relationship in the National Institutes of Health (NIH)-AARP Diet and Health Study. METHODS: Cox proportional hazards models were used to calculate multivariable hazard ratios (HR) and 95% confidence intervals (CI) to investigate dietary fiber and grain intake in relation to head and neck cancer. RESULTS: During approximately 11 years of follow-up, 1,867 (401 women/1,466 men) cases of head and neck cancer were diagnosed. Our data indicated that the relationship between fiber and grain intake and head and neck cancer is modified by sex (p-interactions < 0.001 and 0.001, respectively). Women with higher intake of total fiber and total grains had a lower risk of head and neck cancer (HR (10 g/day) = 0.77, 95% CI = 0.64-0.93; HR (serving/1,000 kcal) = 0.89, 95% CI = 0.80-0.99, respectively); this inverse relation was consistent across subtypes of fiber and grains. Conversely in men, the inverse associations were weaker and nonsignificant. CONCLUSIONS: In the largest prospective cohort study to investigate this relation to date, intake of total fiber and grain foods was inversely associated with head and neck cancer incidence among women, but not among men.

Journal article

Daniel CR, Schwartz KL, Colt JS, Dong LM, Ruterbusch JJ, Purdue MP, Cross AJ, Rothman N, Davis FG, Wacholder S, Graubard BI, Chow WH, Sinha Ret al., 2011, Meat-cooking mutagens and risk of renal cell carcinoma., Br J Cancer, Vol: 105, Pages: 1096-1104

BACKGROUND: High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case-control study conducted in metropolitan Detroit and Chicago. METHODS: Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database. RESULTS: The risk of RCC increased with intake of barbecued meat (P(trend)=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), P(trend)=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (P(interaction)<0.05). We found no association for HCAs or overall meat intake. CONCLUSION: BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC.

Journal article

Cross AJ, Sinha R, Wood RJ, Xue X, Huang WY, Yeager M, Hayes RB, Gunter MJet al., 2011, Iron homeostasis and distal colorectal adenoma risk in the prostate, lung, colorectal, and ovarian cancer screening trial, Cancer Prevention Research

Red meat consumption has been positively associated with colorectal cancer; however, the biological mechanism underlying this relationship is not understood. Red meat is a major source of iron, which may play a role in colorectal carcinogenesis via increased crypt cell proliferation, cytotoxicity, and endogenous N-nitrosation. In a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we prospectively evaluated multiple iron exposure parameters, including dietary intake and serum measures of iron, ferritin, transferrin, total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) in relation to incident colorectal adenoma in 356 cases and 396 matched polyp-free controls. We also investigated variation in eight key genes involved in iron homeostasis in relation to colorectal adenoma in an additional series totaling 1,126 cases and 1,173 matched controls. We observed a positive association between red meat intake and colorectal adenoma [OR comparing extreme quartiles (OR(q4-q1)) = 1.59, 95% CI = 1.02-2.49, P(trend) = 0.03]. Serum TIBC and UIBC were inversely associated with colorectal adenoma (OR(q4-q1) = 0.57, 95% CI = 0.37-0.88, P(trend) = 0.03; and OR(q4-q1) = 0.62, 95% CI = 0.40-0.95, P(trend) = 0.04, respectively). Colorectal adenoma was not associated with serum ferritin, iron, or transferrin saturation or with polymorphisms in genes involved in iron homeostasis. Serum TIBC and UIBC, parameters that have a reciprocal relationship with overall iron load, were inversely related to colorectal adenoma, suggesting that individuals with lower iron status have a reduced risk of developing colorectal adenoma.

Journal article

Aschebrook-Kilfoy B, Cross AJ, Stolzenberg-Solomon RZ, Schatzkin A, Hollenbeck AR, Sinha R, Ward MHet al., 2011, Pancreatic cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study., Am J Epidemiol, Vol: 174, Pages: 305-315

Nitrate and nitrite are precursors of N-nitroso compounds, which induce tumors of the pancreas in animals. The authors evaluated the relation of dietary nitrate and nitrite to pancreatic cancer risk in the NIH-AARP Diet and Health Study. Nitrate and nitrite intakes were assessed at baseline using a 124-item food frequency questionnaire. During approximately 10 years of follow-up between 1995 and 2006, 1,728 incident pancreatic cancer cases were identified. There was no association between total nitrate or nitrite intake and pancreatic cancer in men or women. However, men in the highest quintile of summed nitrate/nitrite intake from processed meat had a nonsignificantly elevated risk of pancreatic cancer (hazard ratio = 1.18, 95% confidence interval: 0.95, 1.47; P-trend = 0.11). The authors observed a stronger increase in risk among men for nitrate/nitrite intake from processed meat at ages 12-13 years (highest quintile vs. lowest: hazard ratio = 1.32, 95% confidence interval: 0.99, 1.76; P-trend = 0.11), though the relation did not achieve statistical significance. The authors found no associations between adult or adolescent nitrate or nitrite intake from processed meats and pancreatic cancer among women. These results provide modest evidence that processed meat sources of dietary nitrate and nitrite may be associated with pancreatic cancer among men and provide no support for the hypothesis in women.

Journal article

Laiyemo AO, Doubeni C, Sanderson AK, Pinsky PF, Badurdeen DS, Doria-Rose VP, Marcus PM, Schoen RE, Lanza E, Schatzkin A, Cross AJet al., 2011, Likelihood of missed and recurrent adenomas in the proximal versus the distal colon., Gastrointest Endosc, Vol: 74, Pages: 253-261

BACKGROUND: Colonoscopy may be less efficacious in reducing colorectal cancer mortality in the proximal compared with the distal colon. A greater likelihood for missed and recurrent adenomas in the proximal colon may contribute to this phenomenon. OBJECTIVE: To examine whether a proximal adenoma is associated with the risk and location of missed and recurrent adenomas. DESIGN: Prospective. SETTING: Polyp Prevention Trial. PARTICIPANTS: A total of 1864 patients with an adenoma at baseline underwent a follow-up colonoscopy 4 years later (adenoma recurrence). Of these, 1731 underwent a clearing colonoscopy 1 year after the baseline examination (missed adenoma). MAIN OUTCOME MEASUREMENTS: Association of baseline adenoma location with the risk and location of adenomas found at colonoscopy performed 1 year and 4 years later. RESULTS: At the year 1 colonoscopy, 598 patients (34.6%) had an adenoma (missed adenoma). Compared with those with a distal-only adenoma at baseline, patients with a proximal-only adenoma at baseline were more likely to have any missed adenomas (relative risk [RR] 1.28; 95% CI, 1.09-1.49) and a proximal-only missed adenoma (RR 2.05; 95% CI, 1.49-2.80). At the year 4 colonoscopy, 733 patients (39.3%) had adenoma recurrence. Patients with a baseline proximal-only adenoma were more likely to have any adenoma recurrence (RR 1.14; 95% CI, 1.00-1.31) and a proximal-only adenoma recurrence (RR 1.52; 95% CI, 1.15-2.02). Sensitivity analyses involving missed adenomas did not materially affect the risk or location of recurrent adenomas at year 4 colonoscopy. LIMITATION: Lesions may still be missed on repeated colonoscopies. CONCLUSIONS: Missed and recurrent adenomas are more likely to be in the proximal colon.

Journal article

Ruder EH, Laiyemo AO, Graubard BI, Hollenbeck AR, Schatzkin A, Cross AJet al., 2011, Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort., Am J Gastroenterol, Vol: 106, Pages: 1340-1350

OBJECTIVES: Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with colorectal cancer; however, the association within colorectal subsites or among higher risk individuals is understudied. We investigated NSAID use and colorectal adenocarcinoma by subsite, and among individuals with a family history of colon cancer in the National Institutes of Health-AARP Diet and Health Study. METHODS: Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer incidence among 301,240 men and women (mean age 62.8 years); including 26,994 individuals with a first-degree relative with a history of colon cancer. We accrued 3,894 colorectal cancer cases during 10 years of follow-up; 372 cases had a first-degree relative with colon cancer. RESULTS: Both aspirin and non-aspirin NSAID use reduced colorectal cancer risk (HR for users compared with non-users=0.91, 95% CI: 0.85, 0.98; HR=0.82, 95% CI: 0.77, 0.87, respectively). Daily aspirin use reduced the risk of cancer in the distal colon (HR=0.84, 95% CI: 0.71, 0.99) and rectum (HR=0.76, 95% CI: 0.64, 0.90); daily non-aspirin NSAID use reduced the risk of both proximal (HR=0.65, 95% CI: 0.54, 0.78) and distal colon cancer (HR=0.69, 95% CI: 0.55, 0.87), but not rectal cancer. Among participants with a first-degree relative with colon cancer, daily use of aspirin was associated with a decreased risk of rectal cancer (HR=0.38, 95% CI: 0.19, 0.78), and daily use of non-aspirin NSAIDs was associated with a decreased risk of colon cancer (HR=0.49, 95% CI: 0.29, 0.82). No protective benefit for daily aspirin use and colon cancer or daily non-aspirin NSAID use and rectal cancer was observed in this higher risk subgroup, although power was limited by small case numbers. CONCLUSIONS: NSAID use was associated with a reduced colorectal cancer risk; the magnitude of this association differed between aspirin and non-aspirin NSAIDs. Daily aspirin

Journal article

Cross AJ, Major JM, Sinha R, 2011, Urinary biomarkers of meat consumption., Cancer Epidemiol Biomarkers Prev, Vol: 20, Pages: 1107-1111

BACKGROUND: Meat intake has been positively associated with incidence and mortality of chronic diseases, including diabetes, heart disease, and several different cancers, in observational studies by using self-report methods of dietary assessment; however, these dietary assessment methods are subject to measurement error. One method to circumvent such errors is the use of biomarkers of dietary intake, but currently there are no accepted biomarkers for meat intake. METHODS: We investigated four analytes (creatinine, taurine, 1-methylhistidine, and 3-methylhistidine) specifically found in meat and excreted in urine. Twenty-four-hour urine samples were collected from 17 individuals on controlled diets containing varying levels of meat: vegetarian (0 g/d), low red meat (60 g/d), medium red meat (120 g/d), and high red meat (420 g/d), as part of two randomized crossover feeding studies. RESULTS: When compared with the low red meat diet or the vegetarian diet, the urinary levels of all four analytes were significantly higher in urine samples collected after 15 days of a high red meat diet (P < 0.0001). Only urinary 1-methylhistidine and 3-methylhistidine were statistically significantly different for every diet type, increasing as the amount of meat in the diet increased (P < 0.01 for 1-methylhistidine and P < 0.05 for 3-methylhistidine). Furthermore, urinary excretion of 1-methylhistidine and 3-methylhistidine elevated with increasing meat intake in every individual. CONCLUSION: Urinary 1-methylhistidine and 3-methylhistidine may be good biomarkers of meat intake. IMPACT: To determine the public health impact of red meat on cancer risk, biomarkers are crucial to estimate true intake; these potential biomarkers should be further investigated in free-living populations.

Journal article

Murphy G, Devesa SS, Cross AJ, Inskip PD, McGlynn KA, Cook MBet al., 2011, Sex disparities in colorectal cancer incidence by anatomic subsite, race and age, INTERNATIONAL JOURNAL OF CANCER, Vol: 128, Pages: 1668-1675, ISSN: 0020-7136

Journal article

Daniel CR, Cross AJ, Koebnick C, Sinha Ret al., 2011, Trends in meat consumption in the USA., Public Health Nutr, Vol: 14, Pages: 575-583

OBJECTIVE: To characterize the trends, distribution, potential determinants and public health implications of meat consumption within the USA. DESIGN: We examined temporal trends in meat consumption using food availability data from the FAO and US Department of Agriculture (USDA), and further evaluated the meat intake by type (red, white, processed) in the National Health and Nutrition Examination Surveys (NHANES) linked to the MyPyramid Equivalents Database (MPED). RESULTS: Overall meat consumption has continued to rise in the USA and the rest of the developed world. Despite a shift towards higher poultry consumption, red meat still represents the largest proportion of meat consumed in the USA (58 %). Twenty-two per cent of the meat consumed in the USA is processed. According to the NHANES 2003-2004, total meat intake averaged 128 g/d. The type and quantities of meat reported varied by education, race, age and gender. CONCLUSIONS: Given the plausible epidemiological evidence for red and processed meat intake in cancer and chronic disease risk, understanding the trends and determinants of meat consumption in the USA, where meat is consumed at more than three times the global average, should be particularly pertinent to researchers and other public health professionals aiming to reduce the global burden of chronic disease.

Journal article

Cross AJ, Freedman ND, Ren J, Ward MH, Hollenbeck AR, Schatzkin A, Sinha R, Abnet CCet al., 2011, Meat Consumption and Risk of Esophageal and Gastric Cancer in a Large Prospective Study, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 106, Pages: 432-442, ISSN: 0002-9270

Journal article

Bobe G, Murphy G, Albert PS, Sansbury LB, Young MR, Lanza E, Schatzkin A, Colburn NH, Cross AJet al., 2011, Do interleukin polymorphisms play a role in the prevention of colorectal adenoma recurrence by dietary flavonols?, EUROPEAN JOURNAL OF CANCER PREVENTION, Vol: 20, Pages: 86-95, ISSN: 0959-8278

Journal article

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