Genotyping of DPYD and UGT1A1 in Brazilian oncological patients: applying pharmacogenomics in an admixed population

Cereser, Vinicius Humberto Bandeira; Moniz, Camila Motta Venchiarutti; Suarez-Kurtz, Guilherme; Estevez-Diz, Maria Del Pilar

doi:10.1590/1806-9282.20251174

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Original Article • Rev. Assoc. Med. Bras. 72 (02) • 2026 • https://doi.org/10.1590/1806-9282.20251174 linkcopy

Genotyping of DPYD and UGT1A1 in Brazilian oncological patients: applying pharmacogenomics in an admixed population

Authorship SCIMAGO INSTITUTIONS RANKINGS

OBJECTIVE: The aim of this study was to determine the frequency of UGT1A1 and DPYD polymorphisms among Brazilian patients with gastrointestinal cancer.

METHODS: UGT1A1 and DPYD polymorphisms were selected due to their importance in the metabolism of fluoropyrimidines and irinotecan, and the existence of available clinical guidelines for dosing recommendations based on genetic testing. Polymorphism rs3918290, rs67376798, rs56038477, rs55886062, rs115232898, and rs887829 were investigated in 100 patients. Allelic discrimination was performed using the TaqMan Assay. Minor allele frequencies were calculated, and metabolic phenotypes were inferred based on the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group guidelines.

RESULTS: For DPYD, rs56038477 (n=100) showed a minor allele frequency of 1.50% (CI 0.51–4.32), rs115232898 (n=49) had a minor allele frequency of 1.02% (CI 0.18–5.56), and rs3918290 (n=100) had a minor allele frequency of 0.50% (CI 0.09–2.78). No variants were observed in rs67376798 (n=100) or rs55886062 (n=44). A total of 4% of patients received a Clinical Pharmacogenetics Implementation Consortium DPYD activity score (AS) of less than 2.0, with 3% of 1.5 AS and 1% of 0.5 AS. For UGT1A1, rs887829 (n=100) revealed a minor allele frequency of 37.5% (CI 31.09–44.39) and 16% of patients with Dutch Pharmacogenetics Working Group poor metabolizer phenotype.

CONCLUSION: The presence of DPYD and UGT1A1 variants is considerable among Brazilian gastrointestinal cancer patients, reinforcing the promising use of pre-therapeutic genetic tests for irinotecan and fluoropyrimidines to avoid severe toxicities related to treatment. Genetic panels for these variants must be continuously updated and adapted for population-specific characteristics.

KEYWORDS:
Dihydropyrimidine dehydrogenase deficiency; UDP-Glucuronosyltransferase 1A1; Pharmacogenetics; Gastrointestinal neoplasms

Gene	SNP	Tested—n	WT homozygous—n (%)	Heterozygous—n (%)	Variant homozygous—n (%)	MAF—% (95%CI)	HWE p-value
DPYD	rs56038477 (c.1236G>A HapB3)	100	97 (97.0%)	3 (3.0%)	0 (0.0%)	1.50 (0.51–4.32)	Not tested (low MAF)
	rs3918290 (c.1905+1G>A DPYD2A*)	100	99 (99.0%)	1 (1.0%)	0 (0.0%)	0.50 (0.09– 2.78)	Not tested (low MAF)
	rs67376798 (c.2846A>T p.D949V)	100	100 (100.0%)	0 (0.0%)	0 (0.0%)	0.00 (0.00–1.88)	Not applicable
	rs115232898 (c.577A>G p.Y186C)	49	48 (97.96%)	1 (2.04%)	0 (0.0%)	1.02 (0.18–5.56)	Not tested (low MAF)
	rs55886062 (c.1679T>G DPYD13*)	44	44 (100.0%)	0 (0.0%)	0 (0.0%)	0.00 (0.00–4.18)	Not applicable
UGT1A1	rs887829 (UGT1A180)*	100	41 (41.0%)	43 (43.0%)	16 (16.0%)	37.50 (31.0–44.39)	0.4084

Gene	Phenotype category	n (%)	Guideline therapeutic dosing recommendation
DPYD	AS=2.0	96 (96%)	CPIC: Use label recommended dosage and administration.*
	AS=1.5	3 (3%)	CPIC: Reduce dose by 25–50%.*
	AS=1.0	0 (0.0%)	CPIC: Reduce dose by 50%.*
	AS=0.5	1 (1%)	CPIC: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.*
	AS=0.0	0 (0.0%)	CPIC: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.*
UGT1A1	Normal metabolizer	41 (41%)	DPWG: No action required.**
	Intermediate metabolizer	43 (43%)	DPWG: No action required.**
	Poor metabolizer	16 (16%)	DPWG: Start with 70% of the normal irinotecan dose.**

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Associação Médica Brasileira R. São Carlos do Pinhal, 324, 01333-903 São Paulo SP - Brazil, Tel: +55 11 3178-6800, Fax: +55 11 3178-6816 - São Paulo - SP - Brazil
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[TFN1] Min: minimum; max: maximum.

[TFN2] ^*
"Pardo" (in Portuguese) refers to the official Brazilian Census category, which includes individuals of mixed European, African, and Indigenous ancestry.

Mean age—years		59.39
Median age (min–max)—years		59 (27–87)
Male sex—n (%)		50 (50.5)
Female sex—n (%)		49 (49.5)
Ethnicity—n (%)
	White	47 (48.5)
	"Pardo"*	29 (29.3)
	Black	14 (14.1)
	Asian	1 (1.0)
	Other	8 (8.1)
Family history of any cancer—n (%)
	Yes	76 (76.8)
	No	23 (23.2)
Presence of other comorbidities—n (%)
	Diabetes mellitus	7 (7.1)
	Arterial hypertension	29 (29.6)
	Chronic obstructive pulmonary disease	5 (5.1)
	Hypercholesterolemia	9 (9.3)