Yusuf I., Pardamean B., Baurley J.W., Budiarto A., Miskad U.A., Lusikooy R.E., Arsyad A., Irwan A., Mathew G., Suriapranata I., Kusuma R., Kacamarga M.F., Cenggoro T.W., McMahan C., Joyner C., Pardamean C.I.
Faculty Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia; Bioinformatics & Data Science Research Center, Bina Nusantara University, Jakarta, DKI Jakarta, Indonesia; Mochtar Riady Institute for Nanotechnology, Pelita Harapan University, Tangerang, Banten, Indonesia; Computer Science Department, BINUS Graduate Program-Master of Computer Science Program, Bina Nusantara University, Jakarta, DKI Jakarta, Indonesia; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, DKI Jakarta, Indonesia; School of Mathematical and Statistical Sciences, Clemson University, Clemson, SC, United States
Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified. © 2021, The Author(s).
Publisher: Nature Research
Volume 11, Issue 1, Art No 9988, Page – , Page Count
Journal Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105767431&doi=10.1038%2fs41598-021-88805-4&partnerID=40&md5=5cfe04dfa64feb06a107117c80cf1096
Type: All Open Access, Gold, Green
Torre, L.A., Global cancer statistics, 2012 (2015) CA Cancer J. Clin., 65, pp. 87-108. , PID: 25651787; Siegel, R.L., Miller, K.D., Jemal, A., Cancer statistics, 2016 (2016) CA Cancer J. Clin., 66, pp. 7-30. , PID: 26742998; Pardamean, B., Baurley, J.W., Pardamean, C.I., Figueiredo, J.C., Changing colorectal cancer trends in Asians (2016) Int. J. Colorectal Disease, 31, p. 1537; Pourhoseingholi, M.A., Increased burden of colorectal cancer in Asia (2012) World J. Gastrointest. Oncol., 4, p. 68. , PID: 22532878; Ng, C.J., Teo, C.H., Abdullah, N., Tan, W.P., Tan, H.M., Relationships between cancer pattern, country income and geographical region in Asia (2015) BMC Cancer, 15, p. 613; Ferlay, J., Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 (2015) Int. J. Cancer, 136, pp. E359-E386; Peters, U., Bien, S., Zubair, N., Genetic architecture of colorectal cancer (2015) Gut, 64, pp. 1623-1636. , COI: 1:CAS:528:DC%2BC28Xlt12iu70%3D, PID: 26187503; Haiman, C.A., Stram, D.O., Exploring genetic susceptibility to cancer in diverse populations (2010) Curr. Opin. Genet. Dev., 20, pp. 330-335. , COI: 1:CAS:528:DC%2BC3cXntlCru7Y%3D, PID: 20359883; Jia, W.-H., Genome-wide association analyses in east Asians identify new susceptibility loci for colorectal cancer (2013) Nat. Genet., 45, p. 191. , COI: 1:CAS:528:DC%2BC38XhvVOqsb7F, PID: 23263487; Zhang, B., Large-scale genetic study in east Asians identifies six new loci associated with colorectal cancer risk (2014) Nat. Genet., 46, p. 533. , COI: 1:CAS:528:DC%2BC2cXotFeru7s%3D, PID: 24836286; Widjaja, S., Yo, H., RM-049Colorectal cancer in Indonesia—A centre report (2016) Ann. Oncol., 27, p. ii97; Phipps, A.I., Colon and rectal cancer survival by tumor location and microsatellite instability: The Colon Cancer Family Registry (2013) Dis. Colon Rectum, 56, pp. 937-944; Hemminki, K., Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes (2010) BMC Cancer, 10, p. 688; Deng, Y., Rectal cancer in asian vs. western countries: Why the variation in incidence? (2017) Curr. Treatment Options Oncol., 18, pp. 1-8; Consortium, G., The genomeasia 100k project enables genetic discoveries across asia (2019) Nature, 576, p. 106; Cui, R., Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population (2011) Gut, 60, pp. 799-805. , COI: 1:STN:280:DC%2BC3MvpvVWmtw%3D%3D, PID: 21242260; Zhu, L., Genetic variant rs7758229 in 6q26-q27 is not associated with colorectal cancer risk in a Chinese population (2013) PLoS ONE, 8. , COI: 1:CAS:528:DC%2BC3sXksFGntr4%3D, PID: 23555006; Hsu, C.-M., Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment (2017) Oncotarget, 8, pp. 74348-74358. , PID: 29088791; Grisanzio, C., Genetic and functional analyses implicate the NUDT11, HNF1B, and SLC22A3 genes in prostate cancer pathogenesis (2012) Proc. Natl. Acad. Sci. USA, 109, pp. 11252-11257. , COI: 1:CAS:528:DC%2BC38Xht1WrurjK, PID: 22730461; Li, Q., Shu, Y., Role of solute carriers in response to anticancer drugs (2014) Mol. Cell Ther., 2, p. 15. , PID: 26056583; Yokoo, S., Significance of organic cation transporter 3 (SLC22A3) expression for the cytotoxic effect of oxaliplatin in colorectal cancer (2008) Drug Metab. Dispos., 36, pp. 2299-2306. , COI: 1:CAS:528:DC%2BD1cXhtlWiu77O, PID: 18710896; Whiffin, N., Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis (2014) Hum. Mol. Genet., 23, pp. 4729-4737. , COI: 1:CAS:528:DC%2BC2cXht1OrsbvI, PID: 24737748; Tanikawa, C., GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12 (2018) Carcinogenesis, 39, pp. 652-660. , COI: 1:CAS:528:DC%2BC1MXls12mtb4%3D, PID: 29471430; Schmit, S.L., Novel common genetic susceptibility loci for colorectal cancer (2019) J. Natl. Cancer Inst., 111, pp. 146-157; Schumacher, F.R., Genome-wide association study of colorectal cancer identifies six new susceptibility loci (2015) Nat. Commun., 6, p. 7138. , PID: 26151821; Sneddon, J.B., Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 14842-14847. , COI: 1:CAS:528:DC%2BD28XhtVyht7fF, PID: 17003113; Stabile, H., Bone morphogenic protein antagonist drm/gremlin is a novel proangiogenic factor (2007) Blood, 109, pp. 1834-1840. , COI: 1:CAS:528:DC%2BD2sXjtFeqt70%3D, PID: 17077323; Ziai, J., Defining the polyposis/colorectal cancer phenotype associated with the ashkenazi GREM1 duplication: Counselling and management recommendations (2016) Genet. Res., 98; Davis, H., Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche (2015) Nat. Med., 21, pp. 62-70. , COI: 1:CAS:528:DC%2BC2cXhvF2js7jI, PID: 25419707; Desmet, F.O., Human Splicing Finder: An online bioinformatics tool to predict splicing signals (2009) Nucleic Acids Res.; Yang, Y., Junjie, P., Sanjun, C., Ma, Y., Long non-coding RNAs in colorectal cancer: Progression and future directions (2017) J. Cancer.; Guo, W., Transcriptome sequencing uncovers a three-long noncoding RNA signature in predicting breast cancer survival (2016) Sci. Rep.; Wan, E.S., Smoking-associated site-specific differential methylation in buccal mucosa in the COPDGene study (2015) Am. J. Respir. Cell Mol. Biol., 53, pp. 246-254; Liu, T.-H., The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell pathogenesis by inhibiting cellular apoptosis (2016) Oncotarget, 7, pp. 25836-25848. , PID: 27028992; Shi, Y., Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth (2015) Oncotarget, 6, pp. 20540-20554. , PID: 26029998; Baurley, J.W., Edlund, C.K., Pardamean, C.I., Conti, D.V., Bergen, A.W., Smokescreen: A targeted genotyping array for addiction research (2016) BMC Genom., 17, p. 145; Das, S., Next-generation genotype imputation service and methods (2016) Nat. Genet., 48, p. 1284. , COI: 1:CAS:528:DC%2BC28XhsVWksL%2FK, PID: 27571263; Consortium, G.P., A global reference for human genetic variation (2015) Nature, 526, p. 68; Loh, P., (2018) Eagle V2.4 User Manual. (Accessed, p. 07. , May; Raj, A., Stephens, M., Pritchard, J.K., faststructure: Variational inference of population structure in large snp data sets (2014) Genetics, 197, pp. 573-589. , PID: 4063916; (2016) GLM: Fitting Generalized Linear Models, , R Foundation for Statistical Computing; Schmit, S.L., Genome-wide association study of colorectal cancer in Hispanics (2016) Carcinogenesis, 37, pp. 547-556; Pruim, R.J., Locuszoom: Regional visualization of genome-wide association scan results (2010) Bioinformatics, 26, pp. 2336-2337. , COI: 1:CAS:528:DC%2BC3cXhtFGhu73E, PID: 2935401; https://doi.org/10.1002/bimj.201900050; Raftery, A.E., Approximate Bayes factors and accounting for model uncertainty in generalised linear models (1996) Biometrika, 83, pp. 251-266; Armagan, A., Dunson, D.B., Lee, J., Generalized double pareto shrinkage (2013) Stat. Sinica, 23, p. 119; https://doi.org/10.1111/j.2517-6161.1977.tb01600.x; Friedman, J., Hastie, T., Tibshirani, R., Regularization paths for generalized linear models via coordinate descent (2010) J. Stat. Softw., 33, p. 1. , PID: 20808728; Polson, N.G., Scott, J.G., Data augmentation for non-gaussian regression models using variance-mean mixtures (2013) Biometrika, 100, pp. 459-471; https://doi.org/10.1007/978-0-387-71887-3_9; Peters, U., Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis (2013) Gastroenterology, 144, pp. 799-807; Whiffin, N., Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis (2014) Hum. Mol. Genet., 23, pp. 4729-4737; Houlston, R.S., Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33 (2010) Nat. Genet., 42, pp. 973-977; Schumacher, F.R., Genome-wide association study of colorectal cancer identifies six new susceptibility loci (2015) Nat. Commun., 6, p. 7138; Real, L.M., A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis (2014) PLoS ONE, 9; Dunlop, M.G., Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk (2012) Nat. Genet., 44, pp. 770-776; Cui, R., Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population (2011) Gut, 60, pp. 799-805; Zanke, B.W., Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24 (2007) Nat. Genet., 39, pp. 989-994; Gruber, S.B., Genetic variation in 8q24 associated with risk of colorectal cancer (2007) Cancer Biol. Ther., 6, pp. 1143-1147. , COI: 1:CAS:528:DC%2BD2sXhsVWks77P, PID: 17630503; Haiman, C.A., A common genetic risk factor for colorectal and prostate cancer (2007) Nat. Genet., 39, pp. 954-956. , NIHMS150003; Tomlinson, I.P., A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3 (2008) Nat. Genet., 40, pp. 623-630; Hutter, C.M., Characterization of the association between 8q24 and colon cancer: Gene–environment exploration and meta-analysis (2010) BMC Cancer, 10, p. 670; Tenesa, A., Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21 (2008) Nat. Genet., 40, pp. 631-637. , NIHMS150003; Wang, H., Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans (2013) Hum. Mol. Genet., 22, pp. 5048-5055; Jaeger, E., Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk (2008) Nat. Genet., 40, pp. 26-28; Broderick, P., A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk (2007) Nat. Genet., 39, pp. 1315-1317
Indexed by Scopus