MTHFD1 c.1958G&gt;A and TCN2 c.776G&gt;C polymorphisms of folate metabolism genes and their implication for oral cavity cancer

Katarzyna Malinowska; Alicja Nowak-Zduńczyk; Anna Merecz-Sadowska; Anna Szczepańska; Dariusz Kaczmarczyk; Katarzyna Bliźniewska-Kowalska; Hanna Zielińska-Bliźniewska

doi:10.2478/ahem-2021-0041

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MTHFD1 c.1958G>A and TCN2 c.776G>C polymorphisms of folate metabolism genes and their implication for oral cavity cancer

Postępy Higieny i Medycyny Doświadczalnej

Volume 76 (2022): Issue 1 (January 2022)

By: Katarzyna Malinowska , Alicja Nowak-Zduńczyk , Anna Merecz-Sadowska , Anna Szczepańska , Dariusz Kaczmarczyk , Katarzyna Bliźniewska-Kowalska and Hanna Zielińska-Bliźniewska

Open Access

|Apr 2022

Figures & Tables

Analysis of the genotype polymorphism MTHFD1 c.1958G>A after hydrolysis with restriction enzyme MspI; lane 1 - marker, lanes 3, 5, 7 - heterozygote GA, lanes 2, 4 - homozygous GG, lane 6 is homozygous AA

Analysis of genotype polymorphism TCN2 c.776G>C after hydrolysis with restriction enzyme ScrFI; lane 1 - marker; lanes 2, 3, 5, 6, 7 - heterozygous CG, lane 4 - homozygous CC, lane 8 is homozygous GG

Table 1

The primers, length of PCR products, and restriction enzymes

Polymorphism	Primers	Product length	Restriction enzyme
MTHFD1 c.1958G>A	Sense 5′-CAC TCC AGT GTT TGT CCA TG-3′ Antisense 5′-GCA TCT TGA GAG CCC TGA C-3′	331 bp	MspI (37°C)
TCN2 c.776G>C	Sense 5′-CAC TTC AAG ACA CAG CAG CCA-3′ Antisense 5′-TCC CCT CAC TGG GAC GTC AAT-3′	568 bp	ScrFI (37°C)

[i] MTHFD1 - methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1; TCN2 - transcobalamin 2

Table 2

Detailed characterization of MTHFD1 and TCN2 gene polymorphisms

Gene	The encoded protein	Number of polymorphism	Location	Function of polymorphism¹	Allele	MAF
MTHFD1	Methylene-tetrahydrofolate-dehydrogenase	rs2236225	14: 63978598	Arg653Gln	G/A	0,46
TCN2	Transcobalamin 2	rs1801198	22: 29341610	Arg259Pro	G/C	0,45

1 According to the Single Nucleotide Polymorphism Database (dbSNP), NCBI

MAF - minor allele frequency; MTHFD1 - methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1; TCN2 - transcobalamin 2

Table 3

Genotype and allele frequencies of MTHFD1 c.1958G>A and TCN2 c.776G>C polymorphisms in oral cavity cancer patients and controls

Genotypes	Controls (%) N=200	Patients (%) N=220/439	OR (95% CI)	P value
MTHFD1c.1958G>A
GG	53 (26.5)	55 (12.5)	1.00
GA	110 (55)	332 (75.6)	2.91 (1.88–4.49)	<0.0001
AA	37 (18.5)	52 (11.9)	1.35 (0.77–2.38)	0.29
G	216 (54)	442 (49)	1.00
A	184 (46)	436 (51)	1.16 (0.91–1.47)	0.23
TCN2 c.776G>C
GG	34 (17)	76 (34.5)	1.00
CG	71 (35.5)	107 (48.7)	0.67 (0.41–1.12)	0.13
CC	95 (47.5)	37 (16.8)	0.17 (0.10–0.30)	<0.0001
G	139 (35)	259 (59)	1.00
C	261 (65)	181 (41)	0.76 (0.58–1.01)	0.06

[i] OR - odds ratio; N – number; P value - probability value; MTHFD1 - methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1; TCN2 - transcobalamin 2

Table 4

Relationships between the patient group and the control group regarding smoking, alcohol consumption, and gender

Variables value	Controls (%)	Patients (%) N=220/439	OR (95%CI)	P value
Tobacco
(N=220)
Non-smokers	150 (75.0)	31 (14.1)	Reference
Smokers	50 (25.0)	189 (85.9)	18.29 (11.13–30.06)	<0.0001
(N=439)
Non-smokers	150 (75.0)	124 (28.2)	Reference
Smokers	50 (25.0)	315 (71.8)	7.62 (5.20–11.16)	<0.0001
Alcohol consumption
(N=220)
No	101 (50.5)	70 (31.8)	Reference
Yes	99 (49.5)	150 (68.2)	2.19 (1.47–3.25)	<0.0001
(N=439)
No	101 (50.5)	149 (33.9)	Reference
Yes	99 (49.5)	290 (66.1)	1.98 (1.41–2.79)	<0.0001
Gender
(N=220)
Female	100 (50.0)	52 (23.6)	Reference
Male	100 (50.0)	168 (76.4)	3.23 (2.13–4.90)	<0.0001
(N=439)
Female	100 (50.0)	124 (28.2)	Reference
Male	100 (50.0)	315 (71.8)	2.54 (1.80–3.59)	<0.0001

[i] OR - odds ratio; N- number; P value - probability value

Table 5

Odds ratio of oral cavity cancer related to MTHFD1 and TCN2 genotypes according to tobacco use, alcohol consumption and gender in patients with head and neck cancer

Risk factor	OR (95%CI) - P value
	MTHFD1c.1958G>A *	TCN2 c.776G>C **
Tobacco
Non-smokers	2.10 (1.09–4.06) P=0.03	0.72 (0.29–1.77) P=0.63
Smokers	2.60 (1.29–5.23) P=0.01	0.15 (0.05–0.45) P<0.0001
Alcohol consumption
No	1.23 (0.60–2.51) P=0.35	0.53 (0.27–1.01) P=0.08
Yes	1.01 (0.57–1.81) P=1	0.26 (0.13–0.52) P<0.0001
Gender
Female	1.77 (0.93–3.39) P=0.1	0.48 (0.22–1.04) P=0.07
Male	2.28 (1.32–3.96) P=0.003	0.33 (0.17–0.61) P=0.003

OR - odds ratio; P value - probability value; MTHFD1 - methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1; TCN2 - transcobalamin 2

* MTHFD1c.1958G>A Reference: GG wild type genotype vs. variants GA+GG

** TCN2 c.776G>C Reference: GG wild type genotype vs. variants GC+CC

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DOI: https://doi.org/10.2478/ahem-2021-0041 | Journal eISSN: 1732-2693

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Language: English

Page range: 30 - 38

Submitted on: Feb 7, 2021

Accepted on: Sep 7, 2021

Published on: Apr 6, 2022

Published by: Hirszfeld Institute of Immunology and Experimental Therapy

In partnership with: Paradigm Publishing Services

Publication frequency: 1 issue per year

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Microbiology and virology,

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Immunology

© 2022 Katarzyna Malinowska, Alicja Nowak-Zduńczyk, Anna Merecz-Sadowska, Anna Szczepańska, Dariusz Kaczmarczyk, Katarzyna Bliźniewska-Kowalska, Hanna Zielińska-Bliźniewska, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 76 (2022): Issue 1 (January 2022)

MTHFD1 c.1958G>A and TCN2 c.776G>C polymorphisms of folate metabolism genes and their implication for oral cavity cancer

Figures & Tables

Fig. 1

Fig. 2

Table 1

Table 2

Table 3

Table 4

Table 5

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