Peter T Campbell

Fred Hutchinson Cancer Research Center, Seattle, Washington, United States

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Publications (65)405.51 Total impact

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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.
    07/2014;
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    ABSTRACT: 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.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 06/2014;
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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.
    06/2014;
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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; · 4.80 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. · 8.52 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 03/2014; · 3.55 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; · 5.08 Impact Factor
  • Peter T Campbell
    Lancet. 01/2014;
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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; · 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 &amp Prevention 10/2013; 22(10):1906-1912. · 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; · 10.73 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; · 18.04 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. · 2.55 Impact Factor
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    ABSTRACT: BACKGROUND: In a previous analysis of 12 cancers in the Cancer Prevention Study II (CPS-II) cohort including follow-up from 1982-2000, having both hay fever and asthma was associated with lower colorectal cancer mortality. The combination of these allergic conditions may be a marker for allergy-related immune responses that could inhibit colorectal carcinogenesis.METHODS: We examined the association of having both hay fever and asthma with colorectal cancer mortality among 1,023,191 participants in CPS-I, followed from 1959-1972, and 1,102,092 participants in CPS-II, now followed from 1982-2008. We also examined associations with colorectal cancer incidence among 174,917 participants in the CPS-II Nutrition Cohort, a subgroup of CPS-II followed from 1992-2007. During the follow-up, there were 5,644 colorectal cancer deaths in CPS-I, 13,558 colorectal cancer deaths in CPS-II, and 3,365 incident colorectal cancer cases in the CPS-II Nutrition Cohort. Cox proportional hazards regression was used to calculate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI).RESULTS: RRs for colorectal cancer mortality associated with having both asthma and hay fever, compared with neither condition, were 0.90 (95% CI, 0.74-1.09) in CPS-I, 0.79 (95% CI, 0.69-0.91) in CPS-II, and 0.83 (95% CI, 0.74-0.92) when results from both cohorts were combined in a meta-analysis. The corresponding RR for colorectal cancer incidence in the CPS-II Nutrition Cohort was 0.90 (95% CI, 0.71-1.14).CONCLUSION: These results support an association between having both hay fever and asthma and modestly lower colorectal cancer mortality.Impact: Research examining other potential markers of allergy-related immune response in relation to colorectal cancer is warranted. Cancer Epidemiol Biomarkers Prev; 22(4); 1-9. ©2013 AACR.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2013; · 4.56 Impact Factor
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    ABSTRACT: PURPOSELittle is known about the association of recreational physical activity or leisure time spent sitting with survival after colorectal cancer diagnosis. This study examined the associations of prediagnosis and postdiagnosis recreational physical activity and leisure time spent sitting with mortality among patients with colorectal cancer. PATIENTS AND METHODS From a cohort of adults without colorectal cancer at baseline in 1992-1993, we identified 2,293 participants who were diagnosed with invasive, nonmetastatic colorectal cancer up to mid-2007. At baseline, before their cancer diagnosis, and again after their cancer diagnosis, participants completed detailed questionnaires that included information concerning recreational physical activity and leisure time spent sitting. RESULTS: relative risk [RR], 0.72; 95% CI, 0.58 to 0.89; postdiagnosis physical activity: RR, 0.58; 95% CI, 0.47 to 0.71). Spending 6 or more hours per day of leisure time sitting compared with fewer than 3 hours per day was associated with higher all-cause mortality (prediagnosis sitting time: RR, 1.36; 95% CI, 1.10 to 1.68; postdiagnosis sitting time: RR, 1.27; 95% CI, 0.99 to 1.64). CONCLUSION More recreational physical activity before and after colorectal cancer diagnosis was associated with lower mortality, whereas longer leisure time spent sitting was associated with higher risk of death.
    Journal of Clinical Oncology 01/2013; · 18.04 Impact Factor
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    ABSTRACT: Low circulating levels of adiponectin and high levels of insulin-like growth factor-1 (IGF-1), C-reactive protein (CRP), and C-peptide have been shown to be related to postmenopausal breast cancer risk, and to partially mediate the obesity-postmenopausal breast cancer association; however, data from prospective studies, especially those limited to non-users of postmenopausal hormones, are sparse. To further evaluate these associations, we measured these markers in a case-control study nested in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort. Plasma samples from 302 postmenopausal breast cancer cases and matched controls were analyzed. None of the women were taking postmenopausal hormones at blood draw. Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Low levels of total adiponectin and high levels of total IGF-1 and CRP were associated with increased breast cancer risk, but associations were not statistically significant. The association with C-peptide was statistically significant (T3 vs. T1: OR=1.63, 95% CI 1.08-2.45; p-value for linear trend=0.001), but was slightly attenuated after further adjustment for BMI (T3 vs. T1: OR=1.51, 95% CI 0.99-2.31; p-value for linear trend=0.004). The association between BMI and breast cancer risk was attenuated toward the null after controlling for C-peptide (from OR=1.43 to OR=1.25 for BMI ≥30 kg/m(2) compared to <25 kg/m>(2)). The elevated risk of postmenopausal breast cancer associated with higher circulating levels of C-peptide is consistent with a role of hyperinsulinemia in breast carcinogenesis, and might account for some of the higher risk associated with obesity.
    International Journal of Molecular Epidemiology and Genetics 01/2013; 4(3):156-66.
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    ABSTRACT: To examine the association between dietary patterns and colorectal cancer (CRC) survival. Cohort study. A familial CRC registry in Newfoundland. 529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to 2003 and followed up until April 2010. Participants reported their dietary intake using a food frequency questionnaire. Dietary patterns were identified with factor analysis. Multivariable Cox proportional hazards models were employed to estimate HR and 95% CI for association of dietary patterns with CRC recurrence and death from all causes, after controlling for covariates. Disease-free survival (DFS) among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest vs the lowest quartile HR 1.82, 95% CI 1.07 to 3.09). No associations were observed with the prudent vegetable or the high-sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest vs the lowest quartile: HR 2.29, 95% CI 1.19 to 4.40) whereas the relationship between overall survival (OS) and this pattern was observed among patients with colon cancer only (the highest vs the lowest quartile: HR 2.13, 95% CI 1.03 to 4.43). Potential effect modification was noted for sex (p value for interaction 0.04, HR 3.85 for women and 1.22 for men). The processed meat dietary pattern prior to diagnosis is associated with higher risk of tumour recurrence, metastasis and death among patients with CRC.
    BMJ Open 01/2013; 3(2). · 1.58 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Heritable factors contribute to development of colorectal cancer (CRC). Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. METHODS: We conducted a genome-wide association study (GWAS) that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. RESULTS: Based on the combined analysis we identified a locus that reached the conventional genome-wide significance level at <5.0 x 10-8: an intergenic region on chromosome 2q32.3, close toNABP1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR]=1.15 per risk allele;P =3.7 x 10-8). We also found evidence for 3 additional loci with P values <5.0 x 10-7: a locus within theLAMC1gene on chromosome 1q25.3 (rs10911251; OR=1.10 per risk allele;P =9.5 x 10-8), a locus within theCCND2gene on chromosome 12p13.32 (rs3217810 per risk allele; OR=0.84;P =5.9 x 10-8), and a locus in theTBX3gene on chromosome 12q24.21 (rs59336, OR=0.91 per risk allele;P =3.7 x 10-7). CONCLUSIONS: In a large GWAS, we associated polymorphisms close toNABP (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms inLAMC1 (this is the second gene in the laminin family to be associated with CRCs),CCND2 (which encodes for cyclin D2), andTBX3 (which encodes a T-box transcription factor and is a target of Wnt signaling to -catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.
    Gastroenterology 12/2012; · 12.82 Impact Factor
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is associated with increased bladder cancer incidence in some, but not all, studies. Many studies had limited statistical power and few examined risk by insulin-use, duration of diabetes or cancer stage. We examined the association between T2DM and bladder cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a large prospective study with information on insulin-use and duration of diabetes. Diabetes and insulin-use were ascertained from a questionnaire at study enrollment in 1992 or 1993 and updated in 1997 and every 2 years thereafter. During follow-up through 2007, 1,852 cases of incident bladder cancer were identified among 172,791 participants. Multivariable adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using extended Cox regression modeling. There were no associations of T2DM with the risk of bladder cancer overall (RR = 1.01, 95% CI: 0.87-1.17), noninvasive disease (RR = 0.93, 95% CI: 0.76-1.14) or invasive disease (RR = 1.13, 95% CI: 0.91-1.40). Compared to participants without T2DM, risk of invasive bladder cancer was higher among participants who had had T2DM for >15 years (RR = 1.63, 95% CI: 1.09-2.43) and among those using insulin (RR = 1.64, 95% CI: 1.18-2.27). These results do not support an association of T2DM with overall bladder cancer incidence, but do suggest positive associations of long-term T2DM and insulin-use or other factors correlated with severe diabetes, with invasive bladder cancer incidence.
    International Journal of Cancer 10/2012; · 6.20 Impact Factor
  • Annals of Epidemiology. 09/2012; 22(9):665.

Publication Stats

1k Citations
405.51 Total Impact Points

Institutions

  • 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
    • Ottawa University
      Kansas, United States
  • 2011–2013
    • Memorial University of Newfoundland
      • • Division of Community Health and Humanities
      • • Faculty of Medicine
      St. John's, Newfoundland and Labrador, Canada
  • 2009–2013
    • American Cancer Society
      • Epidemiology Research Program
      Atlanta, GA, United States
  • 2010
    • Washington University in St. Louis
      San Luis, Missouri, United States
    • German Cancer Research Center
      • Division of Preventive Oncology
      Heidelberg, Baden-Wuerttemberg, Germany
    • American Cancer Society Inc.
      Atlanta, Georgia, United States
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, CA, United States
  • 2004
    • Mount Sinai Hospital, Toronto
      Toronto, Ontario, Canada