Genome‐wide association study and meta‐analysis in Northern European populations replicate multiple colorectal cancer risk loci

Tanskanen, Tomas; Berg, Linda van den; Välimäki, Niko; Aavikko, Mervi; Ness-Jensen, Eivind; Hveem, Kristian; Wettergren, Yvonne; Lindskog, Elinor Bexe; Tõnisson, Neeme; Metspalu, Andres; Silander, Kaisa; Orlando, Giulia; Law, Philip; Tuupanen, Sari; Gylfe, Alexandra E.; Hänninen, Ulrika A.; Cajuso, Tatiana; Kondelin, Johanna; Sarin, Antti‐Pekka; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen–Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin∥, Jukka–Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan M.; Timofeeva, Maria; Meyer, Brian F.; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Tim; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Win, Aung Ko; Hopper, John L.; Jenkins, Mark A.; Newcomb, Polly A.; Gallinger, Steve; Conti, David V.; Schumacher, Fredrick R.; Casey, Graham; Cheadle, Jeremy P.; Dunlop, Malcolm; Tomlinson, Ian; Houlston, Richard S.; Palin, Kimmo; Aaltonen, Lauri A.

doi:10.1002/ijc.31076

Cited by 27 publications

(24 citation statements)

References 24 publications

(69 reference statements)

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“…Moreover, the majority of the specific altered chromosomal regions related with the four defined categories have been related with CRC and/or a higher risk of its development as well (e.g. gain on 8q24 or deletions on 1p21, 1p13 or 1p36) . But more remarkable are gains on 20q13 and deletions on 18p11, two of the most frequently altered regions in PM group, that have been already described by Di et al, presenting similarly within their sample of 15 SCRC patients, in which they defined that synchronous tumors were of different genetic origins, therefore polyclonal.…”

Section: Discussionsupporting

confidence: 58%

“…gain on 8q24 or deletions on 1p21, 1p13 or 1p36). [37][38][39] But more remarkable are gains on 20q13 and deletions on 18p11, two of the most frequently altered regions in PM group, that have been already described by Di et al, 15 presenting similarly within their sample of 15 SCRC patients, in which they defined that synchronous tumors were of different genetic origins, therefore polyclonal.…”

Section: Discussionmentioning

confidence: 71%

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Redefining synchronous colorectal cancers based on tumor clonality

Perea

Garcı́a

Corchete

et al. 2018

Intl Journal of Cancer

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To analyze the possible clonal origin of a part of Synchronous colorectal cancer (SCRC), we studied 104 paired-SCRCs from 52 consecutive patients without hereditary forms of CRC. We used a Single-Nucleotide Polymorphism array to characterize the genomic profiles, and subsequently used a statistical application to define them according to clonality within the same individual. We categorized the ensuing groups according to colonic location to identify differential phenotypes. The SCRC Monoclonal group (M) (19 cases) was divided into Monosegmental (MM) and Pancolonic (MP) groups. The SCRC Polyclonal group (P) (33 cases) was also divided into Monosegmental (PM) and Pancolonic (PP), the first exhibiting preference for left colon. The MM group showed a high rate of mucinous tumors, the lowest mean-number of tumors and associated-polyps, and the worst prognosis. The MP group included the largest mean-number of associated-polyps, best prognosis and familial cancer component. The PM group seemed to be a "frontier" group. Finally, the PP group also exhibited a mucin component, the highest mean-number of tumors (4.6) compared with the mean-number of polyps (7.7), poor prognosis and sporadic cases. Most relevant differential genomic regions within M groups were gains on 1q24 and 8q24, and deletions on 1p21 and 1p23 for MM, while within P were the gains on 7q36 and deletions on 1p36 for PM. The statistical application employed seems to define clonality more accurately in SCRC -more likely to be polyclonal in origin-, and together with the tumor locations, helped us to configure a classification with prognostic and clinical value.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 71%

Redefining synchronous colorectal cancers based on tumor clonality

Perea

Garcı́a

Corchete

et al. 2018

Intl Journal of Cancer

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“…Aspirin use was associated with a reduced risk of CRC on the basis of a meta‐analysis of 39 studies with 151,367 cases [users versus non‐users RR,0.79 (95% CI: 0.74, 0.85); p = 7.8×10 −11 ; I 2 = 91.1%], thus the association was graded as highly suggestive (class II) due to the high heterogeneity between the studies (Table ). The main effect of rs6983267 (8q24) on CRC risk was graded as strong (ABA, equivalent to AAA based on the Venice criteria 16 ) in a meta‐analysis including 13,348 cases and 26,438 controls of European ancestry [OR, 0.84 (95% CI: 0.80, 0.88); p = 7.45×10 −13 ; I 2 = 37.7%] (Table ). Consequently, the interaction between rs6983267 (8q24) and aspirin use was given a moderate prior score (Moderate – 2) and a moderate overall plausibility score (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…the high heterogeneity between the studies ( Table 2). The main effect of rs6983267 (8q24) on CRC risk was graded as strong (ABA, equivalent to AAA based on the Venice criteria 16 ) in a meta-analysis including 13,348 cases and 26,438 controls of European ancestry [OR, 0.84 (95% CI: 0.80, 0.88); p = 7.45×10 −13 ; I 2 = 37.7%] 64 (Table 3). Consequently, the interaction between rs6983267 (8q24) and aspirin use was given a moderate prior score (Moderate -2) and a moderate overall plausibility score (Table 4).…”

Section: Steps Descriptionmentioning

confidence: 99%

Gene–environment interactions and colorectal cancer risk: An umbrella review of systematic reviews and meta‐analyses of observational studies

Yang

Montazeri

et al. 2019

Intl Journal of Cancer

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The cause of colorectal cancer (CRC) is multifactorial, involving both genetic variants and environmental risk factors. We systematically searched the MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases from inception to December 2016, to identify systematic reviews and meta‐analyses of observational studies that investigated gene–environment (G×E) interactions in CRC risk. Then, we critically evaluated the cumulative evidence for the G×E interactions using an extension of the Human Genome Epidemiology Network's Venice criteria. Overall, 15 articles reporting systematic reviews of observational studies on 89 G×E interactions, 20 articles reporting meta‐analyses of candidate gene‐ or single‐nucleotide polymorphism‐based studies on 521 G×E interactions, and 8 articles reporting 33 genome‐wide G×E interaction analyses were identified. On the basis of prior and observed scores, only the interaction between rs6983267 (8q24) and aspirin use was found to have a moderate overall credibility score as well as main genetic and environmental effects. Though 5 other interactions were also found to have moderate evidence, these interaction effects were tenuous due to the lack of main genetic effects and/or environmental effects. We did not find highly convincing evidence for any interactions, but several associations were found to have moderate strength of evidence. Our conclusions are based on application of the Venice criteria which were designed to provide a conservative assessment of G×E interactions and thus do not include an evaluation of biological plausibility of an observed joint effect.

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“…These two variants are both located in the 2 Mb region known to contain multiple susceptibility loci that influence risk of bladder, breast, prostate, colorectal, lung, ovarian, pancreatic, and renal cancer 173–177 . MYC (MYC proto-oncogene, bHLH transcription factor) is the gene located in the closest proximity to the detected variant.…”

Section: Common Low-risk Susceptibility Locimentioning

confidence: 99%

Inherited pancreatic cancer

Chen¹,

Roberts²,

Klein³

2017

Chin. Clin. Oncol.

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Pancreatic cancers arise through a series of genetic events both inherited and acquired. Inherited genetic changes, both high penetrance and low penetrance, are an important component of pancreatic cancer risk, and may be used to characterize populations who will benefit from early detection. Furthermore, pancreatic cancer patients with inherited mutations may be particularly sensitive to certain targeted agents, providing an opportunity to personalized treatment. Family history of pancreatic cancer is one of the strongest risk factors for the disease, and is associated with an increased risk of caners at other sites, including but not limited to breast, ovarian and colorectal cancer. The goal of this chapter is to discuss the importance of family history of pancreatic cancer, and the known genes that account for a portion of the familial clustering of pancreatic cancer.

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Genome‐wide association study and meta‐analysis in Northern European populations replicate multiple colorectal cancer risk loci

Cited by 27 publications

References 24 publications

Redefining synchronous colorectal cancers based on tumor clonality

Redefining synchronous colorectal cancers based on tumor clonality

Gene–environment interactions and colorectal cancer risk: An umbrella review of systematic reviews and meta‐analyses of observational studies

Inherited pancreatic cancer

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