Dataset Information

A Comprehensive Study of the Effect on Colorectal Cancer Survival of Common Germline Genetic Variation Previously Linked with Cancer Prognosis.

ABSTRACT:

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 diagnosis and 128 common genetic variants previously associated with prognosis in genome-wide association studies in different cancer types.

Methods

We studied survival outcomes in a large well-documented, prospective, population-based cohort (5,675 patients with colorectal cancer) with up to 20 years' follow-up.

Results

None of the 128 variants were significantly associated with overall or colorectal cancer-specific survival (P < 5 × 10^-4, Bonferroni-corrected threshold). We observed suggestive evidence (P < 0.05) for eight variants (rs17026425, rs17057166, rs6854845, rs1728400, rs17693104, rs202280, rs6797464, and rs823920) in all colorectal cancer and two variants (rs17026425 and 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 colorectal cancer prognosis.

Impact

Although small effects cannot be excluded, clinically meaningful germline influences on patients with colorectal cancer as a group are unlikely.

SUBMITTER: He Y

PROVIDER: S-EPMC7614160 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Comprehensive Study of the Effect on Colorectal Cancer Survival of Common Germline Genetic Variation Previously Linked with Cancer Prognosis.

He Yazhou Y Timofeeva Maria M Li Xue X Din Farhat V N FVN Blackmur James P JP Vaughan-Shaw Peter P Svinti Victoria V Farrington Susan M SM Campbell Harry H Dunlop Malcolm G MG Theodoratou Evropi E

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20190905 11

<h4>Background</h4>Germline genetic variants may influence pathways of tumor progression common to multiple cancer types. Here, we investigated the association between survival after colorectal cancer diagnosis and 128 common genetic variants previously associated with prognosis in genome-wide association studies in different cancer types.<h4>Methods</h4>We studied survival outcomes in a large well-documented, prospective, population-based cohort (5,675 patients with colorectal cancer) with up t ...[more]

PMID: 31488414

Similar Datasets

Project description:IntroductionPrevious studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.MethodsA literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.ResultsFifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.ConclusionsAlthough no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.

Dataset Information

A Comprehensive Study of the Effect on Colorectal Cancer Survival of Common Germline Genetic Variation Previously Linked with Cancer Prognosis.

Background

Methods

Results

Conclusions

Impact

Publications

A Comprehensive Study of the Effect on Colorectal Cancer Survival of Common Germline Genetic Variation Previously Linked with Cancer Prognosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets