Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma

Rayan Nikkilä^{1

2

3}, Antti Mäkitie^{1

3}, Heikki Joensuu⁴, Saara Markkanen^{5

6}, Klaus Elenius^{7

8

9}, Outi Monni^{4

10

11}, Aarno Palotie^{12

13

14}, Elmo Saarentaus^{1

3

12}; FinnGen; Tuula Salo^{15

16

17

18

19}, Argyro Bizaki-Vallaskangas^{20

21}

Affiliations

¹ Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland.
² Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer and Research, Helsinki, Finland.
³ Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Oncology, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁵ Department of Otolaryngology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶ The Wellbeing Services County of Pirkanmaa, Tampere, Finland.
⁷ Institute of Biomedicine, and MediCity Research Laboratory, University of Turku, Turku, Finland.
⁸ Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
⁹ Department of Oncology, Turku University Hospital, Turku, Finland.
¹⁰ iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
¹¹ Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹² Institute for Molecular Medicine Finland and the Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
¹³ The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁴ Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
¹⁶ Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹⁷ Department of Pathology, HUS Helsinki University Hospital, Helsinki, Finland.
¹⁸ Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.
¹⁹ Medical Research Center, Oulu University Hospital, Oulu, Finland.
²⁰ Department of Otolaryngology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. argyro.bizaki-vallaskangas@tuni.fi.
²¹ The Wellbeing Services County of Pirkanmaa, Tampere, Finland. argyro.bizaki-vallaskangas@tuni.fi.

PMID: 40278994
PMCID: PMC12031715
DOI: 10.1007/s12105-025-01784-0

Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma

Rayan Nikkilä et al. Head Neck Pathol. 2025.

. 2025 Apr 25;19(1):45.

doi: 10.1007/s12105-025-01784-0.

Authors

Affiliations

¹ Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland.
² Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer and Research, Helsinki, Finland.
³ Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Oncology, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁵ Department of Otolaryngology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶ The Wellbeing Services County of Pirkanmaa, Tampere, Finland.
⁷ Institute of Biomedicine, and MediCity Research Laboratory, University of Turku, Turku, Finland.
⁸ Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
⁹ Department of Oncology, Turku University Hospital, Turku, Finland.
¹⁰ iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
¹¹ Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹² Institute for Molecular Medicine Finland and the Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
¹³ The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁴ Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
¹⁶ Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹⁷ Department of Pathology, HUS Helsinki University Hospital, Helsinki, Finland.
¹⁸ Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.
¹⁹ Medical Research Center, Oulu University Hospital, Oulu, Finland.
²⁰ Department of Otolaryngology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. argyro.bizaki-vallaskangas@tuni.fi.
²¹ The Wellbeing Services County of Pirkanmaa, Tampere, Finland. argyro.bizaki-vallaskangas@tuni.fi.

PMID: 40278994
PMCID: PMC12031715
DOI: 10.1007/s12105-025-01784-0

Abstract

Purpose: Limited data from genome-wide association studies (GWAS) focusing on oral tongue squamous cell carcinoma (OTSCC) are available. The present study was conducted to explore genetic associations for OTSCC.

Methods: A GWAS on 376 cases of OTSCC was conducted using the FinnGen Data Freeze-12 dataset. The case-cohort included 205 males and 171 females. Cases with malignancies involving the base of the tongue or lingual tonsil were excluded from the case-cohort. Individuals with no recorded history of malignancy were used as controls (n = 407,067). A Phenome-wide association study (PheWAS) was performed for the lead variants to assess their co-associations with other cancers.

Results: GWAS analysis identified three genome-wide significant loci associated with OTSCC (p < 5 × 10-8), located at 5p15.33 (rs27067 near gene LINC01511), 10q24 (rs1007771191 near RPS3AP36), and 20p12.3 (rs1438070080 near PLCB1), respectively. PheWAS showed associations of rs27067 mainly with prostate cancer (OR = 1.06, p = 5.41 × 10^-7), and seborrheic keratosis (OR = 1.11, p = 1.51 × 10^-11). A co-directional effect with melanoma was also observed (OR = 0.93, p = 6.24 × 10^-5).

Conclusion: The GWAS detected two novel genetic associations with OTSCC. Further research is needed to identify the genes at these loci that contribute to the molecular pathogenesis of OTSCC.

Keywords: FinnGen; Genetic variant; Genome-wide association; Single nucleotide polymorphism; Tongue cancer.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical Approval: The FinnGen study is approved by Finnish Institute for Health and Welfare (permit numbers: THL/2031/6.02.00/2017, THL/1101/5.05.00/2017, THL/341/6.02.00/2018, THL/2222/6.02.00/2018, THL/283/6.02.00/2019, THL/1721/5.05.00/2019 and THL/1524/5.05.00/2020), Digital and population data service agency (permit numbers: VRK43431/2017-3, VRK/6909/2018-3, VRK/4415/2019-3), the Social Insurance Institution (permit numbers: KELA 58/522/2017, KELA 131/522/2018, KELA 70/522/2019, KELA 98/522/2019, KELA 134/522/2019, KELA 138/522/2019, KELA 2/522/2020, KELA 16/522/2020), Findata permit numbers THL/2364/14.02/2020, THL/4055/14.06.00/2020, THL/3433/14.06.00/2020, THL/4432/14.06/2020, THL/5189/14.06/2020, THL/5894/14.06.00/2020, THL/6619/14.06.00/2020, THL/209/14.06.00/2021, THL/688/14.06.00/2021, THL/1284/14.06.00/2021, THL/1965/14.06.00/2021, THL/5546/14.02.00/2020, THL/2658/14.06.00/2021, THL/4235/14.06.00/2021, Statistics Finland (permit numbers: TK-53-1041-17 and TK/143/07.03.00/2020 (earlier TK-53-90-20) TK/1735/07.03.00/2021, TK/3112/07.03.00/2021) and Finnish Registry for Kidney Diseases permission/extract from the meeting minutes on 4th July 2019. The Biobank Access Decisions for FinnGen samples and data utilized in FinnGen Data Freeze 12 include: THL Biobank BB2017_55, BB2017_111, BB2018_19, BB_2018_34, BB_2018_67, BB2018_71, BB2019_7, BB2019_8, BB2019_26, BB2020_1, BB2021_65, Finnish Red Cross Blood Service Biobank 7.12.2017, Helsinki Biobank HUS/359/2017, HUS/248/2020, HUS/430/2021 §28, §29, HUS/150/2022 §12, §13, §14, §15, §16, §17, §18, §23, §58, §59, HUS/128/2023 §18, Auria Biobank AB17-5154 and amendment #1 (August 17 2020) and amendments BB_2021-0140, BB_2021-0156 (August 26 2021, Feb 2 2022), BB_2021-0169, BB_2021-0179, BB_2021-0161, AB20-5926 and amendment #1 (April 23 2020) and it´s modifications (Sep 22 2021), BB_2022-0262, BB_2022-0256, Biobank Borealis of Northern Finland_2017_1013, 2021_5010, 2021_5010 Amendment, 2021_5018, 2021_5018 Amendment, 2021_5015, 2021_5015 Amendment, 2021_5015 Amendment_2, 2021_5023, 2021_5023 Amendment, 2021_5023 Amendment_2, 2021_5017, 2021_5017 Amendment, 2022_6001, 2022_6001 Amendment, 2022_6006 Amendment, 2022_6006 Amendment, 2022_6006 Amendment_2, BB22-0067, 2022_0262, 2022_0262 Amendment, Biobank of Eastern Finland 1186/2018 and amendment 22§/2020, 53§/2021, 13§/2022, 14§/2022, 15§/2022, 27§/2022, 28§/2022, 29§/2022, 33§/2022, 35§/2022, 36§/2022, 37§/2022, 39§/2022, 7§/2023, 32§/2023, 33§/2023, 34§/2023, 35§/2023, 36§/2023, 37§/2023, 38§/2023, 39§/2023, 40§/2023, 41§/2023, Finnish Clinical Biobank Tampere MH0004 and amendments (21.02.2020 & 06.10.2020), BB2021-0140 8§/2021, 9§/2021, §9/2022, §10/2022, §12/2022, 13§/2022, §20/2022, §21/2022, §22/2022, §23/2022, 28§/2022, 29§/2022, 30§/2022, 31§/2022, 32§/2022, 38§/2022, 40§/2022, 42§/2022, 1§/2023, Central Finland Biobank 1-2017, BB_2021-0161, BB_2021-0169, BB_2021-0179, BB_2021-0170, BB_2022-0256, BB_2022-0262, BB22-0067, Decision allowing to continue data processing until 31st Aug 2024 for projects: BB_2021-0179, BB22-0067,BB_2022-0262, BB_2021-0170, BB_2021-0164, BB_2021-0161, and BB_2021-0169, and Terveystalo Biobank STB 2018001 and amendment 25th Aug 2020, Finnish Hematological Registry and Clinical Biobank decision 18th June 2021, Arctic biobank P0844: ARC_2021_1001. Consent to Participate: Study subjects in FinnGen provided informed consent for biobank research, based on the Finnish Biobank Act. Alternatively, separate research cohorts, collected prior the Finnish Biobank Act came into effect (in September 2013) and start of FinnGen (August 2017), were collected based on study-specific consents and later transferred to the Finnish biobanks after approval by Fimea (Finnish Medicines Agency), the National Supervisory Authority for Welfare and Health. Recruitment protocols followed the biobank protocols approved by Fimea. The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa (HUS) statement number for the FinnGen study is Nr HUS/990/2017. Consent for Publication: For this type of study consent for publication is not required.

Figures

**Fig. 1**
Demographics for cases wih OTSCC

**Fig. 2**
Manhattan plot for cases with OTSCC

**Fig. 3**
Regional association plot of OTSCC association on chromosome 5

**Fig. 4**
Regional association plot of OTSCC association on chromosome 10

**Fig. 5**
Regional association plot of OTSCC association on chromosome 20

See this image and copyright information in PMC

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Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma

Affiliations

Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

LinkOut - more resources

Full Text Sources