Evidence map›Paper›PMID 35094705›Full record

ArticleBMC medicine2022

Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization.

Mark Gormley, Tom Dudding, Linda Kachuri, Kimberley Burrows, Amanda H W Chong, Richard M Martin, Steven J Thomas, Jessica Tyrrell, Andrew R Ness, Paul Brennan and 16 more

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

Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

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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

26 authors at 15 institutions in 8 countries.

Mark GormleyMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. mark.gormley@bristol.ac.uk.ORCID 0000-0001-5733-6304
Tom DuddingMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Linda KachuriDepartment of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, USA.
Kimberley BurrowsMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Amanda H W ChongMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Richard M MartinMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Steven J ThomasBristol Dental Hospital and School, University of Bristol, Bristol, UK.
Jessica TyrrellUniversity of Exeter Medical School, RILD Building, RD&E Hospital, Exeter, UK.
Andrew R NessUniversity Hospitals Bristol and Weston NHS Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol, Bristol, UK.
Paul BrennanGenetic Epidemiology Group, World Health Organization, International Agency for Research on Cancer, Lyon, France.
Marcus R MunafòMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Miranda PringBristol Dental Hospital and School, University of Bristol, Bristol, UK.
Stefania BocciaSection of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia.
Andrew F OlshanDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA.
Brenda DiergaardeDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, and UPMC Hillman Cancer Center, Pittsburgh, USA.
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
Geoffrey LiuDalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Eloiza H TajaraDepartment of Molecular Biology, School of Medicine of São José do Rio Preto, São Paulo, Brazil.
Patricia SeverinoAlbert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Tatiana N ToporcovDepartment of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil.
Martin LackoDepartment of Otorhinolaryngology and Head and Neck Surgery, Research Institute GROW, Maastricht University Medical Center, Maastricht, The Netherlands.
Tim WaterboerInfections and Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Nicole BrennerInfections and Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
George Davey SmithMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Emma E VincentMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Rebecca C RichmondMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
University of Bristol · GBUniversity Of Bristol Dental Hospital · GBGerman Cancer Research Center · DEUniversity Hospitals Bristol NHS Foundation Trust · GBUniversity of Toronto · CACentre international de recherche sur le cancer · FRFaculdade de Medicina de São José do Rio Preto · BRHospital Israelita Albert Einstein · BRMaastricht University · NLUniversidade de São Paulo · BRUniversità Cattolica del Sacro Cuore · ITUniversity of California, San Francisco · USUniversity of Exeter · GBUniversity of North Carolina at Chapel Hill · USUPMC Hillman Cancer Center · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
WILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6M
Gene Environment Interaction in Head and Neck CancerR01CA090731 · NCI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI OLSHAN, ANDREW · 2001 to 2005
$4.6M
The role of germline and somatic DNA mutations in oral and oropharyngeal cancersR01DE025712 · NIDCR · INTERNATIONAL AGENCY FOR RES ON CANCER · PI BRENNAN, PAUL JOSEPH, DIERGAARDE, BRENDA B. · 2017 to 2021
$3.3M
Comprehensive Investigation of Multiple Myeloma Genetic Susceptibility in African AmericansK99CA246076 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KACHURI, MIRLINDA · 2020 to 2021
$258k
Academy of Medical Sciences SBF004\1079Cancer Research UK 29019Cancer Research UK C18281/A20919Diabetes UK 17/0005587Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00011/1, MC_UU_00011/5, MC_UU_00011/6, MC_UU_00011/7Medical Research Council MC_UU_00011/5Medical Research Council MC_UU_00011/6Medical Research Council MC_UU_00011/7NCI NIH HHS K99 CA246076NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA097190NCI NIH HHS R01 CA090731NIDCR NIH HHS R01-CA90731NIDCR NIH HHS R01 DE025712NIH HHS P50 CA097190, P30 CA047904 and R01 DE025712Wellcome TrustWellcome Trust 220530/Z/20/ZWorld Health Organization 001
6 · The paper itself

Abstract

backgroundHuman papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR).

methodsGenetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment.

resultsIn univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76).

conclusionsDespite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.

Indexed as

Mendelian Randomization AnalysisOropharyngeal NeoplasmsGenome-Wide Association StudyHumansPolymorphism, Single NucleotideSexual BehaviorSmokingHead and neck cancerMendelian randomizationOropharyngeal cancerSexual behaviour

Identifiers

PMID35094705
PMCPMC8802428
OpenAlexW4220880170

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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.