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A comprehensive study of the effect on colorectal cancer survival of common germline genetic variation previously linked with cancer prognosis

By: Contributor(s): Publication details: 2019-11-01.Subject(s): Genre/Form: Online resources: Summary: BACKGROUND: Germline genetic variants may influence pathways of tumor progression common to multiple cancer types. Here, we investigated the association between survival after colorectal cancer (CRC) diagnosis and 128 common genetic variants previously associated with prognosis in genome-wide association studies (GWAS) in different cancer types. METHODS: We studied survival outcomes in a large well-documented, prospective, population-based cohort (5,675 CRC patients) with up to 20 years follow-up. RESULTS: None of the 128 variants were significantly associated with overall or CRC-specific survival (p<5x10(-4), Bonferroni-corrected threshold). We observed suggestive evidence (p<0.05) for eight variants (rs17026425, rs17057166, rs6854845, rs1728400, rs17693104, rs202280, rs6797464, rs823920) in all CRC and two variants (rs17026425, rs6854845) in rectal cancer that were concordant with previous reports. CONCLUSIONS: Given good statistical power (>0.80 for 75% of variants), this study indicates that most previously reported variants associated with cancer survival have limited influence on CRC prognosis. IMPACT: Although small effects cannot be excluded, clinically meaningful germline influences on CRC patients as a group are unlikely.
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/pmc/articles/PMC7614160/

/pubmed/31488414

BACKGROUND: Germline genetic variants may influence pathways of tumor progression common to multiple cancer types. Here, we investigated the association between survival after colorectal cancer (CRC) diagnosis and 128 common genetic variants previously associated with prognosis in genome-wide association studies (GWAS) in different cancer types. METHODS: We studied survival outcomes in a large well-documented, prospective, population-based cohort (5,675 CRC patients) with up to 20 years follow-up. RESULTS: None of the 128 variants were significantly associated with overall or CRC-specific survival (p<5x10(-4), Bonferroni-corrected threshold). We observed suggestive evidence (p<0.05) for eight variants (rs17026425, rs17057166, rs6854845, rs1728400, rs17693104, rs202280, rs6797464, rs823920) in all CRC and two variants (rs17026425, rs6854845) in rectal cancer that were concordant with previous reports. CONCLUSIONS: Given good statistical power (>0.80 for 75% of variants), this study indicates that most previously reported variants associated with cancer survival have limited influence on CRC prognosis. IMPACT: Although small effects cannot be excluded, clinically meaningful germline influences on CRC patients as a group are unlikely.

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