Table 1.

Racial frequency of genotypes that influence the pharmacogenetics and therapeutic targets of PDAC. This table demonstrates differences in allele frequencies between African and European ancestral populations and it is impact on enzymatic functional differences. These allele frequencies are associated with common drugs used to treat patients with PDAC and have implications on pharmacogenetics and therapeutic targets during treatment.

Genotype	Activity	Allelic frequencies (%)		Associated drug class
		African ancestry	European ancestry
DPD deficient genotypes	Decreased Enzymatic activity	4-12%16, 18, 77	3-5%16, 18, 77	Fluoropyrimidines (5-FU and Capecitabine)
TYMS: 2R/2R expression	Decreased TS activity	28%18	23.8%18	Fluoropyrimidines (5-FU and Capecitabine)
MMR deficiency	Impaired DNA repair genes	9.6%78	10.4%78	Pembrolizumab
MSI	Impaired DNA repair gene	3.6-12%79–81	14%79, 80	Pembrolizumab
PALB2	Impaired DNA repair gene	6.6 Median TPM12, 13	5.5 median TPM12, 13	PARP-I
HRD: BRCA 1 mutation	Impaired DNA repair gene	3.54%82	2.15% Non-Ashkenazi 5.6% Ashkenazi82	PARP-I, Platinums (Oxaliplatin and Cisplatin)
HRD: BRCA 2 mutation	Impaired DNA repair gene	4.55%82	1.50% Non-Ashkenazi; 3.7% Ashkenazi82	PARP-I, Platinums (Oxaliplatin and Cisplatin)
ERCC1 mutation	Impaired DNA repair gene	73.5 TPM1 12, 13	63.8 TPM12, 13	Platinums
ERCC2 mutation	Impaired DNA repair gene	10.1 TPM12, 13	14.0 TPM12, 13	Platinums
UGT1A1*28 expression	Decreased enzymatic activity	13-43%21, 83	8-39%21, 83	Irinotecan
UGT1A1* 93	Decreased enzymatic activity	34%21	27%21	Irinotecan
UGT1A1*6	Decreased enzymatic activity	0.1%21	1%21	Irinotecan
POLA2 2089G>A	Gemcitabine resistance during Knockdown	18%27, 32	18%27	Gemcitabine
DCTD 315T>C	Gemcitabine pathway variant	48%27	25%27	Gemcitabine
SLC281 1543 G>A	Gemcitabine pathway variant	9%27	2%27	Gemcitabine
SLC281 1576 T>C	Gemcitabine pathway variant	0%27	47%27	Gemcitabine
SLC282 283A>C	Gemcitabine pathway variant	8%27	34%27	Gemcitabine
TYMS 149del (ttaaag)	Gemcitabine pathway variant	56%27	27%27	Gemcitabine
SLC 29A1 −1345 C>G	Transporters, increased gene activity in vitro	8%30, 84	0%30, 84	Gemcitabine
SLC 29A1 −1050 G>A	Transporter, increased gene activity in vitro	19%30	0%30	Gemcitabine
RRM1 −524 T>C	Decreased drug response	27%30	36%30	Gemcitabine
CDA −897 C>A	Reduced CDA activity in vivo		2% together30	Gemcitabine
CDA 79 A>C (Lys27Gln)	Decreased drug response	4-10.8%30	30-36%30	Gemcitabine, Fluorouracil
CDA 208 G>A (Ala70Thr)	Decreased CDA activity	12.5%30	0%30	Gemcitabine, Fluorouracil
CDA 435 C>T (Thr145Thr)	Lower response rates	35-36. 7%30, 85	30-32.5%30, 85	Gemcitabine, Fluorouracil
CYP2C8*3	Lower Paclitaxel Clearance	0-238, 39	1-13%38, 39	Nab-Paclitaxel
CYP2C8*2	Lower Paclitaxel Clearance	2%38	18%38	Nab-Paclitaxel
NTRK genes	Fusion gene, oncogenic	0.34%63	0.28%63	NTRK fusion inhibitors

¹TPM: Transcripts Per Million