Hoffmeister, Michael

AbstractBackgroundPostmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location.MethodsWe pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided.ResultsAmong postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors.ConclusionsWe observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.

AbstractBackgroundBody mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.MethodsTo improve statistical power and interpretation for gene‐environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype‐Tissue Expression Project for all genes with heritability ≥1%. We used a mixed‐effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI‐CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2.ResultsAmong 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10−5), PSMC5 (P = 4.51 × 10−4) and CD33 (P = 2.71 × 10−4) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10−5) and SCN1B (P = 2.76 × 10−4) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10−5).ConclusionsAggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

Abstract Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93–0.98; P = 5.2 × 10−4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92–0.97; P = 5.4 × 10−5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03–1.08; P = 3.3 × 10−5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01–1.07; P = 2.5 × 10−3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01–1.06; P = 1.2 × 10−2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.

Abstract Background: Smoking has been associated with colorectal cancer (CRC) risk; but limited evidence has shown the association between smoking and molecular subtypes of CRC. Methods: We analyzed 9,422 CRC cases and 9,950 controls from 10 observational studies. Multinomial logistic regression analysis was performed to assess the association between sex-study-specific quartiles of pack years of smoking and risk of CRC molecular subtypes, using non-smokers as reference group, adjusting for age, sex, and study. Known oncogenic mutations in four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutations, KRAS mutations, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. Case-only analysis was also performed to estimate heterogeneity in risk of molecular subtypes of CRC. Results: Compared with controls, higher pack years of smoking were statistically significantly associated with increased CRC risk when stratified, individually, by all four markers, and the associations got stronger with higher quartiles pack years (p-trend&lt;0.001). Associations between smoking and CRC risk also differed significantly among molecular subtypes. Compared to nonsmokers, the risk of BRAFmut CRC was 83% higher for smokers within the highest quartile of pack-years (OR=1.83; 95% CI: 1.50, 2.25), and 29% higher for BRAFwt CRC (OR=1.29; 95% CI: 1.17, 1.43; Ratio of ORs (ROR)=1.45; 95% CI: 1.18, 1.17; p=3.45x10-4). Similarly, heavy pack-years of smoking was associated with almost two times higher risk of CIMP-high CRC (OR=1.93; 95% CI: 1.60, 2.31), but only 33% higher risk of CIMP-low/negative CRC (OR=1.33; 95% CI: 1.19, 1.48; ROR=1.49; 95% CI: 1.24, 1.79; p=1.72x10-5). The association between smoking and CRC was also stronger in MSI-high tumors (ORMSI-H=1.65; 95% CI: 1.36, 2.00; ORMSI-L/MSS=1.37; 95% CI: 1.23, 1.52; ROR=1.22; 95% CI: 1.00, 1.48; p=0.046). In contrast, the association between smoking and CRC risk was stronger for KRASwt (OR=1.43; 95% CI: 1.27, 1.60), than KRASmut tumors (OR=1.18; 95% CI: 1.02, 1.37; ROR=0.83; 95% CI: 0.71, 0.97; p =0.016). When combining tumor markers, smoking was found to be significantly associated with higher risk of colorectal tumors from the serrated pathway. Conclusion: In this largest study with a total of 19,372 subjects, we found that heavier pack years of smoking was associated with increased risk of all CRC molecular subtypes. Smokers with heavier pack-years of smoking had particularly higher risk of CRC subtypes with BRAF mutation and CIMP-high, suggesting smoking may be particularly involved in the development of these subtypes of colorectal tumor. Citation Format: Xiaoliang Wang, Efrat Amitay, Barbara L. Banbury, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Jenny Chang-Claude, Steven J. Gallinger, Graham G. Giles, Tabitha A. Harrison, John L. Hopper, Mark A. Jenkins, Yi Lin, Reiko Nishihara, Polly A. Newcomb, Shuji Ogino, Lori C. Sakoda, Robert E. Schoen, Martha L. Slattery, Steven N. Thibodeau, Bethany Van Guelpen, Michael O. Woods, Li Hsu, Michael Hoffmeister, Ulrike Peters. Smoking is associated with risks of molecular subtypes of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 630.

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p‐value = 3.5 × 10−6) and rs2189517 (in RAD51B) with rectal cancer risk (p‐value = 5.7 × 10−6). The results had statistical significance close to the Bonferroni corrected p‐value of 5.8 × 10−6. Ninety‐four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis‐eQTL suggesting possible mechanisms of carcinogenesis.

Abstract Genome-wide association studies of colorectal cancer (CRC) have identified over 50 susceptibility loci. These variants represent only a small fraction of total heritability for CRC. Gene-environment (GxE) interaction studies may help identify novel loci and biological interactions that give insight to the pathogenesis of CRC. Previous genome-wide GxE studies with dietary factors have identified interactions between loci and processed meat consumption and alcohol; however, limited statistical power remains a primary concern. Set-based SNP testing has the potential to increase statistical power to detect GxE interactions by aggregating functionally relevant SNPs. In this large pooled analysis using 14 case-control and nested case-control studies, we incorporated functional information from the transcriptome prediction tool, PrediXcan, into a novel set-based approach for testing GxE interactions. We used variant weights from the PrediXcan models of tissue-specific gene expression in the transverse colon as a priori variant information for a set-based GxE approach. We restricted our analysis to variants in the PrediXcan transverse colon gene models (n = 4,842). This discovery phase included 10,360 CRC and advanced adenoma cases, and 11,183 controls of European ancestry from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry. All 14 studies were analyzed together in a pooled data set using the Mixed Effects Score Tests for interactions. We tested for gene interactions with sex- and study- specific quartiles of dietary intake of red meat (servings/day), processed meat (servings/day), vegetables (servings/day), fruits (servings/day), and fiber (g/day). We detected two genes with suggestive interactions (false discovery rate (FDR) &lt; 0.2) with intake of red meat and risk of CRC: Superoxide Dismutase 2 (SOD2) and Ubiquitin Conjugating Enzyme E2 H (UBE2H). No interactions at FDR &lt; 0.2 were observed for processed meat, vegetables, fruits, or fiber. The SOD2 gene, which encodes an enzyme important in apoptotic signaling and clearing of reactive oxygen species, may regulate response to colonic exposure to heme iron or increased bile acid from high-fat content in red meat. UBE2H is part of the ubiquitin-proteasome system that has a role in Wnt signaling, which can be mediated by heme iron in red meat and is commonly found dysregulated in cancer. These findings highlight the efficacy of integrating functional information and set-based testing for novel discovery of genes interacting with known dietary risk factors of CRC. We plan to replicate these findings in additional studies. Citation Format: Paneen S. Petersen, Yu-Ru Su, Sonja I. Berndt, Stephanie A. Bien, Hermann Brenner, Graham Casey, Andrew T. Chan, Jenny Chang-Claude, Jane C. Figueiredo, Steven J. Gallinger, Robert W. Haile, Tabitha A. Harrison, Michael Hoffmeister, Mark A. Jenkins, Amit D. Joshi, Sébastien Küry, Loic Le Marchand, Yi Lin, Noralane M. Lindor, Polly A. Newcomb, John D. Potter, Robert Schoen, Martha L. Slattery, Stephen N. Thibodeau, Emily White, Li Hsu, Ulrike Peters, CCFR, GECCO. Interactions between genetic predictors of gene expression and dietary factors associated with risk of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5268.

Abstract Background Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer (CRC). Genome-wide interaction analysis (GxE) has identified a few variants that may modify the effects of NSAIDs on CRC risk. However, limited statistical power remains a concern. Restricting analyses by using functional genomic information to aggregate variants into biologically relevant sets can reduce the number of tests, thereby increasing statistical power. We tested the interactions between variant models of gene expression and NSAIDs use on CRC risk. Methods Functional weights of each variant were estimated using PrediXcan based on jointly measured transcriptomes and genomes data of transverse colon tissues from the Genotype-Tissue Expression (GTEx) Project for all genes with sufficient heritability (≥1%). A mixed-effects model was used to assess the GxE effects in a gene among 9,917 incident CRC cases and 10,533 controls from 17 (nested) case-control studies from the Colon Cancer Family Registry (CCFR) and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). GxE analysis was done by modeling the interaction between predicted gene expression and NSAID use (fixed effects), and residual variant-specific GxE effects that are not accounted for (random effects). Regular user of aspirin and/or non-aspirin NSAIDs was compared to non-regular users. False discovery rate (FDR) was used to account for multiple comparison and FDR≤0.2 was considered genome-wide significant. Secondary analysis was performed on significant genes and duration of use among users. Results Regular use of aspirin was higher among controls (30.3%) compared to cases (24.3%). Among the 4,842 genes tested, SORD significantly modified the effect of regular use of aspirin on CRC risk (p-interaction = 1.45×10-5; FDR=0.07). The SORD gene encodes sorbitol dehydrogenase (SORD), which oxidizes sorbitol to fructose in the polyol pathway. Decreased SORD concentrations were previously observed to dramatically increase in colorectal adenoma cells when compared to normal mucosa cells, suggesting the involvement of dysregulated polyol metabolisms in colorectal tumorigenesis. However, the duration of aspirin use was not statistically significantly associated with SORD gene expression on CRC risk (p=0.149) among 5,560 aspirin users. No significant interactions were observed between genetically determined colon gene expression levels and any NSAID use or non-aspirin NSAID use at FDR&lt;0.2. Conclusions Incorporating functional information, we discovered a novel gene that may interact with aspirin use to confer CRC risk. These findings provide preliminary support for new biological insights that could help understand the chemopreventive mechanisms of aspirin on CRC. We aim to replicate these findings in additional studies. Citation Format: Xiaoliang Wang, Yu-Ru Su, Andrew T. Chan, Stephanie Bien, Sonja I. Bernt, Hermann Brenner, Graham Casey, Jenny Chang-Claude, Steven J. Gallinger, Robert W. Haile, Tabitha A. Harrison, Michael Hoffmeister, Mark A. Jenkins, Amit Joshi, Yi Lin, Noralane M. Lindor, Loic Le Marchand, Hongmei Nan, Polly A. Newcomb, John D. Potter, Martha L. Slattery, Steve N. Thibodeau, Emily White, Li Hsu, Ulrike Peters. Functionally informed genome-wide interaction analysis of nonsteroidal anti-inflammatory drugs on colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2965.

Abstract Over 50 genetic variants have been associated with colorectal cancer (CRC) risk through genome-wide association studies (GWAS), yet these variants represent only a fraction of the total estimated heritability. CRC is a heterogenous disease with diverse tumor etiology. Assessing genetic risk in molecular subtypes may help to identify novel loci and characterize genetic risk among tumor subtypes. We used microsatellite instability (MSI), an established CRC classifier with etiological and therapeutic relevance, to define CRC subtypes for GWAS analyses. We conducted a case-case analysis to estimate odds ratios (OR) and 95% confidence intervals (CI) for association of genome-wide variants with microsatellite stable (MSS) versus unstable (MSI) carcinomas. We ran an inverse-variance weighted fixed-effects meta-analysis across GWAS in a discovery set of 4,163 population-based CRC cases with harmonized microsatellite instability (MSI) marker and imputed genotype data. For each analysis, we used log-additive logistic regression, adjusting for age, sex, and principal components to account for population substructure. We then followed up with replication of 102 SNPs that reached p-values less than 5x10-6 in 1,698 cases. A total of 845 (20.3%) cancer cases were microsatellite unstable in the discovery population and 174 (10.2%) were unstable in the replication population. No variants reached the genome-wide significance level of 5x10-8 in the discovery set. However, we identified two variants that reached a Bonferroni corrected p-value of 4.0x10-4 in the replication set. This included one variant in MLH1 (Replication: OR=1.74, 95% CI=1.53-1.98, p=1.63x10-5; Discovery+Replication: OR=1.45, 95% CI=1.37-1.54, p=9.76x10-11) and one variant in LOC105377645 (Replication: OR=1.70, 95% CI=1.49-1.94, p=5.13x10-5; Discovery+Replication: OR=1.45, 95% CI=1.37-1.54, p=9.76 x 10-11). The MLH1 gene is a DNA mismatch repair gene implicated in Lynch Syndrome, the hallmark of which is microsatellite instability. This is the first genome-wide scan to identify a common variant in MLH1 that is associated with CRC. This variant (minor allele frequency, MAF = 23% in this all European ancestry population) is located in the 5'-untranslated region of MLH1 and is thought to act as a long-range regulator of DCLK3, a potential tumor driver gene. The second variant, located in LOC105377645 with an MAF of 22%, is in an uncharacterized region of the genome and has not previously been implicated in cancer development. These findings suggest that accounting for molecular heterogeneity is important for discovery and characterization of genetic variants associated with CRC risk. We plan to run polytomous regression analyses, increase our sample size, and further investigate CRC subtypes by CIMP, BRAF mutation, KRAS mutation status. Citation Format: Tabitha A. Harrison, Yiwen Lu, Chenjie Zeng, Flora Qu, Kristin Anderson, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Graham G. Giles, Bethany Van Guelpen, Michael Hoffmeister, Mark A. Jenkins, Noralane M. Lindor, Roger L. Milne, Polly A. Newcomb, Reiko Nishihara, Michael O. Woods, Shuji Ogino, John D. Potter, Martha L. Slattery, Wei Sun, Stephen N. Thibodeau, Li Hsu, Ulrike Peters. Genome-wide association study by colorectal carcinoma subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 229.

Abstract Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Abstract The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) in collaboration with the Colorectal Cancer Family Registry (CCFR) aims to identify genetic variants and environmental risk factors that impact colorectal cancer (CRC). Over 30 studies from North America, Europe, and Australia participate in GECCO. These studies have collected clinical, epidemiological, and survival data, as well as blood and tumor biospecimens, for over 80,000 CRC cases and controls. The current study aims to conduct targeted deep sequencing of tumors and matching normal DNA to identify recurrent and novel somatic and germline variants in 4,200 CRC cases. To achieve this goal, an AmpliSeq targeted sequencing panel of 1.12 Mbp was constructed to sequence the coding regions of 190 significantly mutated genes identified from whole exome sequencing datasets generated by the Nurses’ Health Study and Health Professional’s Follow-up Study, and The Cancer Genome Atlas. The panel also covers coding regions of 15 genes with germline high penetrance mutations in CRC, 54 regions to detect CRC-related copy number alterations (CNAs), and microsatellite and homopolymer repeat regions to identify defective DNA mismatch repair. Primers were also included to detect Fusobacterium nucleatum DNA in tumor biopsies, as F. nucleatum is thought to promote CRC carcinogenesis. Sequencing of the DNA libraries on Illumina HiSeq 2500 produced a mean coverage of greater than 500X for tumor DNA and 100X for normal DNA, with &gt;85% of the bases covered at the target at 50x. So far, targeted sequencing of &gt;1,500 DNA samples from CRC tumors and normal tissues has identified recurrent and novel somatic mutations, germline genetic variants, and hypermutation status of the tumors due to defective DNA mismatch repair or pathogenic mutations in the POLE gene. Targeted sequencing has also allowed quantification of the F. nucleatum DNA in tumor biopsies; the results were validated by a multiplex QPCR assay. At the AACR annual meeting, we will present targeted sequencing results generated from the first two GECCO-participating studies (n=1,300 cases). These data will be valuable for future association testing of somatic mutations, CNAs, hypermutation status, and F. nucleatum with germline genetic variants, lifestyle, and environmental risk factors and survival. This large study will allow development of better strategies for diagnosis, treatment, and prevention of CRC. Citation Format: Syed H. Zaidi, Wei Sun, Jeroen Huyghe, Catherine S. Grasso, Quang Trinh, Charles Connolly, Amy French, Jasmine Mu, Marios Giannakis, Eve Shinbrot, Ivan Borozan, Michael J. Quist, Hermann Brenner, Daniel Buchanan, Peter Campbell, Andrew Chan, Jenny Chang-Claude, Vincent Ferretti, Charles Fuchs, Andrea Gsur, Marc Gunter, Tabitha Harrison, Michael Hoffmeister, Wen-Yi Huang, Paul Krzyzanowski, Stephen Lee, Mathieu Lemire, Jessica Miller, Danielle Pasternack, Cherie Teney, Elaine Mardis, Polly Newcomb, Lincoln Stein, Lee Timms, David Wheeler, Christina Yung, Niha Zubair, Levi Garraway, Shuji Ogino, Li Hsu, Steven Gallinger, Stephen Thibodeau, Thomas Hudson, Ulrike Peters. Targeted deep sequencing of colorectal tumor tissues to study associations of tumor subtypes with germline genetic, lifestyle, and environmental risk factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1286. doi:10.1158/1538-7445.AM2017-1286