Evidence map›Paper›PMID 27894333›Full record

ArticleHuman genomics2016

Head-and-neck squamous cell carcinoma risk in smokers: no association detected between phenotype and AHR, CYP1A1, CYP1A2, or CYP1B1 genotype.

Lucia F Jorge-Nebert, Ge Zhang, Keith M Wilson, Zhengwen Jiang, Randall Butler, Jack L Gluckman, Susan M Pinney, Daniel W Nebert

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 35% of its field
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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. The Multifarious Link between Cytochrome P450s and Cancer.Oxidative medicine and cellular longevity · 2020
    Review
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

8 authors at 2 institutions in 1 country.

Lucia F Jorge-NebertDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH, 45267-0056, USA.
Ge ZhangDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH, 45267-0056, USA.
Keith M WilsonDepartment of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, 45267-0528, USA.
Zhengwen JiangDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH, 45267-0056, USA.
Randall ButlerDepartment of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267-0533, USA.
Jack L GluckmanDepartment of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, 45267-0528, USA.
Susan M PinneyDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH, 45267-0056, USA.
Daniel W NebertDepartment of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH, 45267-0056, USA. dan.nebert@uc.edu.
University of Cincinnati Medical Center · USUniversity of Cincinnati · US

Funding

REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY RESEARCHP30ES006096 · NIEHS · UNIVERSITY OF CINCINNATI · PI YADAV, JAGJIT S · 1992 to 2022
$35.4M
Human HNSCC: CYP1B1/1A1/1A2 and AHR Gene PolymorphismsR01DE016325 · NIDCR · UNIVERSITY OF CINCINNATI · PI NEBERT, DANIEL W. · 2006 to 2008
$759k
NIDCR NIH HHS R01 DE016325NIEHS NIH HHS P30 ES006096
6 · The paper itself

Abstract

backgroundHead-and-neck squamous cell carcinoma (HNSCC) differs between smokers and nonsmokers in etiology and clinical presentation. Because of demonstrated unequivocal involvement in smoking-induced cancer in laboratory animals, four candidate genes--AHR, CYP1A1, CYP1A2, and CYP1B1--were selected for a clinical genotype-phenotype association study of HNSCC risk in smokers. Thirty-six single-nucleotide variants (mostly tag-SNPs) within and near these four genes [16 (AHR), 4 (CYP1A1), 4 (CYP1A2), and 12 (CYP1B1)] were chosen.

methodsExtreme discordant phenotype (EDP) method of analysis was used to increase statistical power. HNSCC patients--having smoked 1-40 cigarette pack-years--represented the "highly-sensitive" (HS) population; heavy smokers having smoked ≥80 cigarette-pack-years without any type of cancer comprised the "highly-resistant" (HR) group. The vast majority of smokers were intermediate and discarded from consideration. Statistical tests were performed on N = 112 HS and N = 99 HR DNA samples from whole blood.

conclusionsAmong the four genes and flanking regions--one haploblock, ACTTGATC in the 5' portion of CYP1B1, retained statistical significance after 100,000 permutations (P = 0.0042); among our study population, this haploblock was found in 36.4% of African-American, but only 1.49% of Caucasian, HNSCC chromosomes. Interestingly, in the 1000 Genomes Project database, frequency of this haplotype (in 1322 African and 1006 Caucasian chromosomes) is 0.356 and 0.003, respectively. This study represents an excellent example of "spurious association by population stratification". Considering the cohort size, we therefore conclude that the variant alleles chosen for these four genes, alone or in combinations, are not statistically significantly associated with risk of cigarette-smoking-induced HNSCC.

Indexed as

Basic Helix-Loop-Helix ProteinsCarcinoma, Squamous CellCase-Control StudiesCytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2Cytochrome P-450 CYP1B1Gene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHaplotypesHead and Neck NeoplasmsHumansLinkage DisequilibriumPolymorphism, Single NucleotideReceptors, Aryl HydrocarbonSmokingAHR protein, humanBasic Helix-Loop-Helix ProteinsCYP1A1 protein, humanCYP1A2 protein, humanCYP1B1 protein, humanCytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2Cytochrome P-450 CYP1B1Receptors, Aryl HydrocarbonAHR geneCandidate-gene approach to genotype-phenotype associationCigarette smokingCYP1A1CYP1A2CYP1B1 genesExtreme discordant phenotype methodHead-and-neck squamous cell carcinoma (HNSCC)Population stratificationTag-SNPs (single nucleotide polymorphisms)

Identifiers

PMID27894333
PMCPMC5127090
OpenAlexW2559647210

What OpenQuestion holds

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LicenceCC BY
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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.