Peter T Campbell

Duke University, Durham, North Carolina, United States

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Publications (77)575.35 Total impact

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    ABSTRACT: Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene × environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. Colorectal cancer. Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P = 6.2 × 10-28) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 × 10-9 for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P = 7.7 × 10-33) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 × 10-9 for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 × 10-30) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P = .76). In this genome-wide investigation of gene × environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.
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    ABSTRACT: Although oxidative stress is implicated in colorectal carcinogenesis, human studies on associations of individual prooxidants and antioxidants with colorectal cancer (CRC) have been inconclusive. We incorporated individual environmental factors known to affect oxidative stress into 4 oxidative balance scores (OBS) and investigated their associations with CRC in the Cancer Prevention Study II Nutrition Cohort. During 1999-2009, a total of 1,109 incident CRC cases were identified among 80,063 participants in the Nutrition Cohort who had completed detailed questionnaires. Four OBS with different weighting methods (equal weights, literature review-based, a posteriori data-based, and weights based on Bayesian analysis) were created by combining 16 dietary and nondietary lifestyle factors. Higher values for all 4 OBS, representing more antioxidant exposures than prooxidant exposures, were associated with 41%-53% lower risks of CRC; for example, the relative risk for the highest OBS quartile versus the lowest in the Bayesian analysis was 0.50 (95% confidence interval: 0.41, 0.61). The associations were more modest when OBS was restricted to either dietary or nondietary components. These results, obtained using comprehensive summary measures of oxidative balance-especially considering the similarity of the findings derived using the different weighting methods-support the hypothesis that a predominance of antioxidant lifestyle exposures (both dietary and nondietary) over prooxidant lifestyle exposures reduces risk of CRC. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    American Journal of Epidemiology 02/2015; DOI:10.1093/aje/kwu318 · 4.98 Impact Factor
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    ABSTRACT: Active smoking is associated with higher colorectal cancer risk, but its association with survival after colorectal cancer diagnosis is unclear. We investigated associations of smoking, before and after diagnosis, with all-cause and colorectal cancer-specific mortality among colorectal cancer survivors. From a cohort of adults who were initially free of colorectal cancer, we identified 2,548 persons diagnosed with invasive, nonmetastatic colorectal cancer between baseline (1992 or 1993) and 2009. Vital status and cause of death were determined through 2010. Smoking was self-reported on the baseline questionnaire and updated in 1997 and every 2 years thereafter. Postdiagnosis smoking information was available for 2,256 persons (88.5%). Among the 2,548 colorectal cancer survivors, 1,074 died during follow-up, including 453 as a result of colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, prediagnosis current smoking was associated with higher all-cause mortality (relative risk [RR], 2.12; 95% CI, 1.65 to 2.74) and colorectal cancer-specific mortality (RR, 2.14; 95% CI, 1.50 to 3.07), whereas former smoking was associated with higher all-cause mortality (RR, 1.18; 95% CI, 1.02 to 1.36) but not with colorectal cancer-specific mortality (RR, 0.89; 95% CI, 0.72 to 1.10). Postdiagnosis current smoking was associated with higher all-cause (RR, 2.22; 95% CI, 1.58 to 3.13) and colorectal cancer-specific mortality (RR, 1.92; 95% CI, 1.15 to 3.21), whereas former smoking was associated with all-cause mortality (RR, 1.21; 95% CI, 1.03 to 1.42). This study adds to the existing evidence that cigarette smoking is associated with higher all-cause and colorectal cancer-specific mortality among persons with nonmetastatic colorectal cancer. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 02/2015; DOI:10.1200/JCO.2014.58.3831 · 17.88 Impact Factor
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    ABSTRACT: Background: The CpG Island Methylator Phenotype (CIMP) represents a subset of colorectal cancers (CRCs) characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known. Methods: We measured the CIMP status of 3,119 primary population-based CRC tumors from the multinational Colon Cancer Family Registry. Etiologic heterogeneity was assessed by a case-case study comparing risk factor frequency of CRC cases with CIMP and non-CIMP tumors using logistic regression to estimate the case-case odds ratio (ccOR). Results: We found associations between tumor CIMP status and MSI-H (ccOR=7.6), BRAF V600E mutation (ccOR=59.8), proximal tumor site (ccOR=9) (all p<0.0001), female sex (ccOR=1.8; 95% CI=1.5-2.1), older age (ccOR=4.0 comparing over 70 years vs under 50; 95% CI=3.0-5.5) and family history of CRC (ccOR=0.6, 95% CI=0.5-0.7). While use of NSAIDs varied by tumor CIMP status for both males and females (p=0.0001 and p=0.02, respectively), use of multi-vitamin or calcium supplements did not. Only for female CRCs was CIMP status associated with increased pack-years of smoking (trend p < 0.001) and body mass index (BMI) (trend p = 0.03). Conclusions: The frequency of several CRC risk factors varied by CIMP status, and the associations of smoking and obesity with tumor subtype were evident only for females. Impact: Differences in the associations of a unique DNA methylation-based subgroup of CRC with important lifestyle and environmental exposures increase understanding of the molecular pathologic epidemiology of this heavily methylated subset of CRCs. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 01/2015; DOI:10.1158/1055-9965.EPI-14-1161 · 4.32 Impact Factor
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    ABSTRACT: To better understand colorectal cancer etiology and prognosis, archived surgical tissues were collected from Cancer Prevention Study II (CPS-II) Nutrition Cohort participants who were diagnosed with colorectal cancer. Herein, the methodology for this collection is described to help inform other efforts to collect tissues. The main components to accruing tissue were: (i) obtaining consent from participants or next-of-kin; (ii) contacting hospitals to request materials; and (iii) pathology review and laboratory processing. In CPS-II, we identified 3,643 participants diagnosed with colorectal cancer between 1992/1993 and 2009. Of these, tissue could not be sought from cases verified through state cancer registry linkage (N = 1,622), because of insufficient information on tissue location. We sought tissue from the 2,021 cases verified using medical records, and received tissue from 882. When hospitals were contacted within 10 years of diagnosis, we received 87% of tissue materials; beyond that 10-year mark, we received 32%. Compared with the 2,761 colorectal cancer cases without tissue, the 882 cases with tissue were more likely to be alive, diagnosed more recently during follow-up, and had less-advanced staged disease. Cases with and without tissues were similar with respect to age at diagnosis, smoking, body mass index, physical activity, and other epidemiologic factors. Some of the most important elements in forming a tissue repository included having the cases' hospital contact and surgical accession information as well as contacting patients/next-of-kin and hospitals within 10 years of surgery. This tissue repository will serve as an important resource for colorectal cancer studies. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology." Cancer Epidemiol Biomarkers Prev; 23(12); 2694-702. ©2014 AACR. ©2014 American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 12/2014; 23(12):2694-702. DOI:10.1158/1055-9965.EPI-14-0541 · 4.32 Impact Factor
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    ABSTRACT: Purpose In a recent analysis of a large clinical database, postdiagnosis aspirin use was associated with 57% lower prostate cancer-specific mortality (PCSM) among men diagnosed with nonmetastatic prostate cancer. However, information on this association remains limited. We assessed the association between daily aspirin use and PCSM in a large prospective cohort. Patients and Methods This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study-II Nutrition Cohort in 1992 or 1993 and June 2009. Aspirin use was reported at enrollment, in 1997, and every 2 years thereafter. During follow-up through 2010, there were 441 prostate cancer deaths among 8,427 prostate cancer cases with information on prediagnosis aspirin use and 301 prostate cancer deaths among 7,118 prostate cancer cases with information on postdiagnosis aspirin use. Results Compared with no aspirin use, neither prediagnosis nor postdiagnosis daily aspirin use were statistically significantly associated with PCSM (prediagnosis use, multivariable-adjusted hazard ratio (HR) = 0.92, 95% CI 0.72 to 1.17, postdiagnosis use, HR = 0.98; 95% CI, 0.74 to 1.29). However, among men diagnosed with high-risk cancers (>= T3 and/or Gleason score >= 8), postdiagnosis daily aspirin use was associated with lower PCSM (HR = 0.60; 95% CI, 0.37 to 0.97), with no clear difference by dose (low-dose, typically 81 mg per day, HR = 0.50; 95% CI, 0.27 to 0.92, higher dose, HR = 0.73; 95% CI, 0.40 to 1.34). Conclusion A randomized trial of aspirin among men diagnosed with nonmetastatic prostate cancer was recently funded. Our results suggest any additional randomized trials addressing this question should prioritize enrolling men with high-risk cancers and need not use high doses. (C) 2014 by American Society of Clinical Oncology
    Journal of Clinical Oncology 10/2014; 32(33). DOI:10.1200/JCO.2013.54.8875 · 17.88 Impact Factor
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    ABSTRACT: Background: Calcium intake may reduce risk of colorectal cancer (CRC), but the mechanisms remain unclear. Studies of interaction between calcium intake and single nucleotide polymorphisms (SNPs) in calcium-related pathways have yielded inconsistent results. Methods: To identify gene-calcium interactions, we tested interactions between ~2.7 million SNPs across the genome with self-reported calcium intake (from dietary or supplemental sources) in 9,006 CRC cases and 9,503 controls of European ancestry. To test for multiplicative interactions, we used multivariable logistic regression and defined statistical significance using the conventional genome-wide α=5E-08. Results: After accounting for multiple comparisons, there were no statistically significant SNP-interactions with total, dietary, or supplemental calcium intake. Conclusions: We found no evidence of SNP-interactions with calcium intake for CRC risk in a large population of 18,509 individuals. Impact: These results suggest that in genome-wide analysis common genetic variants do not strongly modify the association between calcium intake and CRC in European populations.
    Cancer Epidemiology Biomarkers & Prevention 09/2014; DOI:10.1158/1055-9965.EPI-14-0893 · 4.32 Impact Factor
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    Peter T Campbell
    The Lancet 08/2014; 384(9945). DOI:10.1016/S0140-6736(14)61172-7 · 39.21 Impact Factor
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    ABSTRACT: Background: Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer (CRC). Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. Methods: Data on 9160 cases and 9280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, post-menopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed-effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. Results: None of the permutation-adjusted p-values reached statistical significance. Conclusions: The associations between recently identified genetic susceptibility loci and CRC are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. Impact: Results suggest little evidence of gene-environment interaction involving recently identified susceptibility loci for CRC.
    Cancer Epidemiology Biomarkers & Prevention 07/2014; 23(9). DOI:10.1158/1055-9965.EPI-14-0062 · 4.32 Impact Factor
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    ABSTRACT: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with reduced risk of colorectal neoplasia. Previous studies have reported that polymorphisms in NSAID-metabolizing enzymes central to NSAID metabolism including UDP-glucuronosyltransferases (UGT) and cytochrome P450 (CYP) 2C9 may modify this protective effect. We investigated whether 35 functionally relevant polymorphisms within CYP2C9 and UGT genes were associated with colorectal cancer risk or modified the protective effect of NSAIDs on colorectal cancer susceptibility, using 1,584 colorectal cancer cases and 2,516 unaffected sibling controls from the Colon Cancer Family Registry. A three-SNP genotype in UGT1A6 (G–A–A; Ala7–Thr181–Arg184) and the Asp85 variant in UGT2B15 increased the risk of colorectal cancer (OR 3.87; 95% CI 1.04–14.45 and OR 1.34; 95% CI 1.10–1.63, respectively). We observed interactions between UGT1A3 Thr78Thr (A>G) and NSAID use (P-interaction = 0.02), a three-SNP genotype within UGT2B4 and ibuprofen use (P-interaction = 0.0018), as well as UGT2B15 Tyr85Asp (T>G) and aspirin use (P-interaction = 0.01). The interaction with the UGT2B4 and the UGT2B15 polymorphisms were noteworthy at the 25% FDR level. This study highlights the need for further pharmacogenetic studies to identify individuals who might benefit from NSAID use as part of developing effective strategies for prevention of colorectal neoplasia. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 07/2014; 53(7). DOI:10.1002/gcc.22167 · 3.84 Impact Factor
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    ABSTRACT: Purpose Higher calcium, vitamin D, and dairy product intakes are associated with lower colorectal cancer incidence, but their impacts on colorectal cancer survival are unclear. We evaluated associations of calcium, vitamin D, and dairy product intakes before and after colorectal cancer diagnosis with all-cause and colorectal cancer-specific mortality among colorectal cancer patients. Patients and Methods This analysis included 2,284 participants in a prospective cohort who were diagnosed with invasive, nonmetastatic colorectal cancer after baseline (1992 or 1993) and up to 2009. Mortality follow-up was through 2010. Prediagnosis risk factor information was collected on the baseline questionnaire. Postdiagnosis information was collected via questionnaires in 1999 and 2003 and was available for 1,111 patients. Results A total of 949 participants with colorectal cancer died during follow-up, including 408 from colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, postdiagnosis total calcium intake was inversely associated with all-cause mortality (relative risk [RR] for those in the highest relative to the lowest quartiles, 0.72; 95% CI, 0.53-0.98; P-trend = .02) and associated with marginally statistically significant reduced colorectal cancer-specific mortality (RR, 0.59; 95% CI, 0.33 to 1.05; P-trend = .01). An inverse association with all-cause mortality was also observed for postdiagnosis milk intake (RR, 0.72; 95% CI, 0.55 to 0.94; P-trend = .02), but not vitamin D intake. Prediagnosis calcium, vitamin D, and dairy product intakes were not associated with any mortality outcomes. Conclusion Higher postdiagnosis intakes of total calcium and milk may be associated with lower risk of death among patients with nonmetastatic colorectal cancer. (C) 2014 by American Society of Clinical Oncology
    Journal of Clinical Oncology 06/2014; 32(22). DOI:10.1200/JCO.2014.55.3024 · 17.88 Impact Factor
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    ABSTRACT: Background: Individuals with a family history of colorectal cancer (CRC) in first-degree relatives have an elevated risk of developing CRC themselves, particularly CRC exhibiting high microsatellite instability (MSI-high). Given that MSI-high CRC is associated with a favorable prognosis, it is plausible that having a family history of CRC could, in turn, be favorably associated with CRC survival. Methods: This study comprised N=4284 incident CRC cases enrolled in the Colon Cancer Family Registry via population-based cancer registries. Using Cox proportional hazards regression, we evaluated the association between family history and both overall and disease-specific survival, accounting for MSI status and tumor site via stratified analyses and statistical adjustment. Results: There was no evidence of association between family history and overall [hazard ratio (HR)=0.92, 95% confidence interval (CI): 0.79-1.08] or disease-specific survival (HR=1.03, 95% CI: 0.85-1.24) for all cases combined, after adjustment for MSI status or tumor site. Only for rectal cancer cases was CRC family history modestly associated with more favorable overall survival (HR=0.75, 95% CI: 0.56-0.99). Conclusions: Although individuals with a family history of CRC were more likely to have MSI-high tumors than those with non-familial disease, this did not translate to a survival benefit. Impact: Overall, there is no evidence that family history of CRC is associated with CRC survival; however, specific mechanisms underlying family history may have prognostic impact and merit further study.
    Cancer Epidemiology Biomarkers & Prevention 06/2014; 23(8). DOI:10.1158/1055-9965.EPI-14-0533 · 4.32 Impact Factor
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    ABSTRACT: To examine associations of simple hysterectomy and hysterectomy with bilateral salpingo-oophorectomy (BSO), relative to no surgery, with total and site-specific cancer risk in the Cancer Prevention Study-II Nutrition Cohort. We examined associations of hysterectomy with BSO and simple hysterectomy with total and site-specific cancer risk in 66,802 postmenopausal women from the Cancer Prevention Study-II Nutrition Cohort. During a median follow-up of 13.9 years, 8,621 cancers were diagnosed. Hysterectomy with BSO performed at any age (1,892 cases), compared with no hysterectomy (n=5,586 cases), is associated with a 10% reduction in all cancers (relative risk [RR] 0.90, 95% confidence interval [CI] 0.85-0.96). This inverse association does not hold if the surgery occurred at ages 55 years or older (583 cases; RR 1.02, 95% CI 0.94-1.12). Hysterectomy with BSO (715 cases) was associated with a 20% reduction in breast cancer performed at any age (RR 0.80, 95% CI 0.73-0.88). Hysterectomy without BSO was associated with a deceased cancer risk only if performed at age 45 years or younger (541 cases; RR 0.88, 95% CI 0.80-0.97) and overall was associated with a decreased risk of breast cancer (419 cases; RR 0.86, 95% CI 0.76-0.96). In a large prospective study, hysterectomy with BSO before age 55 years, relative to no surgery, is associated with a lower risk of total cancer. This information, particularly the lower risk in women younger than 45 years, should be considered in counseling women about ovarian management at the time of surgery. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 05/2014; DOI:10.1097/AOG.0000000000000270 · 4.37 Impact Factor
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    ABSTRACT: Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.
    PLoS Genetics 04/2014; 10(4):e1004228. DOI:10.1371/journal.pgen.1004228 · 8.17 Impact Factor
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    ABSTRACT: Background:Smoking is a risk factor for incident colorectal cancer (CRC); however, it is unclear about its influence on survival after CRC diagnosis.Methods:A cohort of 706 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Smoking and other relevant data were collected by questionnaire after cancer diagnosis, using a referent period of '2 years before diagnosis' to capture pre-diagnosis information. Molecular analyses of microsatellite instability (MSI) status and BRAF V600E mutation status were performed in tumour tissue using standard techniques. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards regression, controlling for major prognostic factors.Results:Compared with never smokers, all-cause mortality (overall survival, OS) was higher for current (HR: 1.78; 95% CI: 1.04-3.06), but not for former (HR: 1.06; 95% CI: 0.71-1.59) smokers. The associations of cigarette smoking with the study outcomes were higher among patients with 40 pack-years of smoking (OS: HR: 1.72; 95% CI: 1.03-2.85; disease-free survival (DFS: HR: 1.99; 95% CI: 1.25-3.19), those who smoked 30 cigarettes per day (DFS: HR: 1.80; 95% CI: 1.22-2.67), and those with microsatellite stable (MSS) or MSI-low tumours (OS: HR: 1.38; 95% CI: 1.04-1.82 and DFS: HR: 1.32; 95% CI: 1.01-1.72). Potential heterogeneity was noted for sex (DFS HR: 1.68 for men and 1.01 for women: P for heterogeneity=0.04), and age at diagnosis (OS: HR: 1.11 for patients aged <60 and 1.69 for patients aged 60: P for heterogeneity=0.03).Conclusions:Pre-diagnosis cigarette smoking is associated with worsened prognosis among patients with CRC.British Journal of Cancer advance online publication, 21 January 2014; doi:10.1038/bjc.2014.6 www.bjcancer.com.
    British Journal of Cancer 01/2014; DOI:10.1038/bjc.2014.6 · 5.08 Impact Factor
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    ABSTRACT: Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.
    The British journal of nutrition 10/2013; DOI:10.1017/S0007114513003462 · 3.45 Impact Factor
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    ABSTRACT: Epidemiologic evidence supports an inverse association between physical activity and postmenopausal breast cancer. Whether associations exist for moderate activities, such as walking, and whether associations differ by estrogen receptor (ER) status, body mass index (BMI, kg/m(2)), adult weight gain, or use of postmenopausal hormones (PMH) is unclear. The relation between time spent sitting and breast cancer also is unclear. Among 73,615 postmenopausal women in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, 4,760 women were diagnosed with breast cancer between 1992 and 2009. Extended Cox regression was used to estimate multivariable-adjusted relative risks (RR) of breast cancer in relation to total recreational physical activity, walking, and leisure-time sitting. Differences in associations by ER status, BMI, weight gain, and PMH use were also evaluated. The most active women (those reporting >42 MET-hours/week physical activity) experienced 25% lower risk of breast cancer than the least active [0-<7 MET-hours/week; 95% confidence interval (CI), 0.63-0.89; Ptrend = 0.01]. Forty-seven percent of women reported walking as their only recreational activity; among these women, a 14% lower risk was observed for ≥7 hours/week relative to ≤3 hours/week of walking (95% CI, 0.75-0.98). Associations did not differ by ER status, BMI, weight gain, or PMH use. Sitting time was not associated with risk. These results support an inverse association between physical activity and postmenopausal breast cancer that does not differ by ER status, BMI, weight gain, or PMH use. The finding of a lower risk associated with ≥7 hours/week of walking may be of public health interest. Cancer Epidemiol Biomarkers Prev; 22(10); 1906-12. ©2013 AACR.
    Cancer Epidemiology Biomarkers & Prevention 10/2013; 22(10):1906-1912. DOI:10.1158/1055-9965.EPI-13-0407 · 4.56 Impact Factor
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    ABSTRACT: Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10(-4) was used to determine statistical significance of the associations. Two correlated SNPs-rs10090154 and rs4242382-in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.
    Gut 08/2013; DOI:10.1136/gutjnl-2013-305189 · 13.32 Impact Factor
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    ABSTRACT: PURPOSERed and processed meat intake is convincingly associated with colorectal cancer (CRC) incidence, but its impact on prognosis after CRC diagnosis is unknown. We examined associations of red and processed meat consumption, self-reported before and after cancer diagnosis, with all-cause and cause-specific mortality among men and women with invasive, nonmetastatic CRC. PATIENTS AND METHODS Participants in the Cancer Prevention Study II Nutrition Cohort reported information on diet and other factors at baseline in 1992-1993, 1999, and 2003. Participants with a verified CRC diagnosis after baseline and up to June 30, 2009, were observed for mortality through December 31, 2010.ResultsAmong 2,315 participants diagnosed with CRC, 966 died during follow-up (413 from CRC and 176 from cardiovascular disease [CVD]). In multivariable-adjusted Cox proportional hazards regression models, red and processed meat intake before CRC diagnosis was associated with higher risks of death as a result of all causes (top v bottom quartile, relative risk [RR], 1.29; 95% CI, 1.05 to 1.59; Ptrend = .03) and from CVD (RR, 1.63; 95% CI, 1.00 to 2.67; Ptrend = .08) but not CRC (RR, 1.09; 95% CI, 0.79 to 1.51; Ptrend = 0.54). Although red and processed meat consumption after CRC diagnosis was not associated with mortality, survivors with consistently high (median or higher) intakes before and after diagnosis had a higher risk of CRC-specific mortality (RR, 1.79; 95% CI, 1.11 to 2.89) compared with those with consistently low intakes. CONCLUSION This study suggests that greater red and processed meat intake before diagnosis is associated with higher risk of death among patients with nonmetastatic CRC.
    Journal of Clinical Oncology 07/2013; 31(22). DOI:10.1200/JCO.2013.49.1126 · 17.88 Impact Factor
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    ABSTRACT: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.
    World Journal of Gastroenterology 06/2013; 19(21):3241-8. DOI:10.3748/wjg.v19.i21.3241 · 2.43 Impact Factor

Publication Stats

2k Citations
575.35 Total Impact Points

Institutions

  • 2014
    • Duke University
      Durham, North Carolina, United States
    • Emory University
      • Winship Cancer Institute
      Atlanta, Georgia, United States
  • 2007–2014
    • Fred Hutchinson Cancer Research Center
      • • Division of Public Health Sciences
      • • Cancer Prevention Program
      • • Prevention Center
      Seattle, Washington, United States
    • Samuel Lunenfeld Research Institute
      Toronto, Ontario, Canada
  • 2013
    • Cancer Prevention Institute of California
      Fremont, California, United States
  • 2011–2012
    • Memorial University of Newfoundland
      • • Faculty of Medicine
      • • Division of Community Health and Humanities
      Saint John, New Brunswick, Canada
  • 2010–2011
    • American Cancer Society
      • Epidemiology Research Program
      Atlanta, Georgia, United States
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
  • 2004
    • Mount Sinai Hospital, Toronto
      Toronto, Ontario, Canada