Evidence map›Paper›PMID 39825500›Full record

SynthesisHuman molecular genetics2025

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Anna Prizment, Abby Standafer, Conghui Qu, Kathleen M Beutel, Shuo Wang, Wen-Yi Huang, Annika Lindblom, Rachel Pearlman, Bethany Van Guelpen, Alicja Wolk and 10 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Human molecular genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Anna PrizmentLaboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Abby StandaferLaboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Conghui QuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, 98019, USA.
Kathleen M BeutelLaboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Shuo WangLaboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Wen-Yi HuangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, MSC 9776, Bethesda, MD, 20892, USA.
Annika LindblomDepartment of Molecular Medicine and Surgery, Karolinska Institutet, K1 Molekylär medicin och kirurgi, K1 MMK Klinisk genetik, 171 76 Stockholm, Sweden.
Rachel PearlmanDepartment of Internal Medicine, Division of Human Genetics, The Ohio State University Comprehensive Cancer Center, 2012 Kenny Rd, Columbus, OH, 43221, USA.
Bethany Van GuelpenDepartment of Radiation Sciences, Oncology Unit, 27C, Målpunkt QC11, NUS, Norrlands universitetssjukhus, Umeå University, 901 85 Umeå, Sweden.
Alicja WolkInstitute of Environmental Medicine, Karolinska Institutet, C6 Institutet för miljömedicin, C6 CVD-NUT-EPI Wolk, 171 77 Stockholm, Sweden.
Daniel D BuchananDepartment of Clinical Pathology, University of Melbourne Center for Cancer Research, University of Melbourne, 305 Grattan Street, Melbourne, Victoria, 3010, Australia.
Robert C GrantUHN-Princess Margaret Cancer Centre, University of Toronto, 7-811 700 University Ave, Toronto, Ontario, M5G 1X6, Canada.
Stephanie L SchmitGenomic Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Mail Code NE50, Cleveland, OH, 44195, USA.
Elizabeth A PlatzDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD, 21205, USA.
Corinne E JoshuDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD, 21205, USA.
David J CouperDepartment of Biostatistics, University of North Carolina at Chapel Hill, 123 W Franklin Street, Suite 450, CB #8030, Chapel Hill, NC, 27516, USA.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, 98019, USA.
Timothy K StarrMasonic Cancer Center, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Patricia ScottMasonic Cancer Center, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Nathan PankratzLaboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.ORCID 0000-0001-5958-693X

Funding

Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
Role of genetic and epigenetic alterations in CFTR in colorectal cancerR21CA256749 · NCI · UNIVERSITY OF MINNESOTA · PI PRIZMENT, ANNA, SCOTT, PATRICIA M · 2021 to 2022
$406k
NCI NIH HHS R21 CA256749NCI NIH HHS R21CA256749NCI NIH HHS U01 CA167551NIH HHSUniversity of Minnesota Academic Health CenterWhiteside Institute for Clinical Research
6 · The paper itself

Abstract

backgroundIndividuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

methodsUsing population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk. For replication, we used whole exome sequencing data from UK Biobank (UKB; 5126 cases and 20 504 controls matched 4:1 based on genetic distance, age, and sex), and extended our analyses to all other heterozygous CFTR variants annotated as CF-causing.

resultsIn our meta-analysis of GECCO-CORECT-CCFR-ARIC, the odds ratio (OR) for CRC risk associated with Phe508del was 1.11 (P = 0.010). In our UKB replication, the OR for CRC risk associated with Phe508del was 1.28 (P = 0.002). The sequencing data from UKB also revealed an association between the presence of any other single CF-causing variant (excluding Phe508del) and CRC risk (OR = 1.33; P = 0.030). When stratifying CFTR variants by functional class, class I variants (no protein produced) had a stronger association (OR = 1.77; p = 0.002), while class II variants (misfolding and retention of the protein in the endoplasmic reticulum) other than Phe508del (OR = 1.75; p = 0.107) had similar effect size as Phe508del, and variants in classes III-VI had non-significant ORs less than 1.0 and/or were not present in cases.

conclusionsCF-causing heterozygous variants, especially class I variants, are associated with a modest but statistically significant increased CRC risk. More research is needed to explain the biology underlying these associations.

Indexed as

Colorectal NeoplasmsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorGenetic Predisposition to DiseaseAdultAgedCase-Control StudiesExome SequencingFemaleHumansMaleMiddle AgedRisk FactorsCFTR protein, humanCystic Fibrosis Transmembrane Conductance Regulatorcolorectal cancerhaploinsufficiencyheterozygous CFTR variantsrare variant burden testwhole exome sequencing data

Identifiers

PMID39825500
PMCPMC11924186

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.