World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 5, October 2024, pages 792-800

Analysis of Pancreatic Cancer Genetic Risk Factors in a Multi-Ethnic Population Sample

Figure 1. Representative images of VDR expression in pancreatic cancer according to VDR variants’ haplotype. VDR haplotypes are shown as rs2228570/rs731236. (a) Normal VDR expression in a healthy pancreatic specimen. (b-j) Representative images of pancreatic cancer cell block sections according to VDR haplotypes. All images were captured at × 400 magnification.

**Table 1.** Demographic and Clinical Characteristics of Pancreatic Cancer and Healthy Control Cohorts
Criteria	Pancreatic cancer patients (n = 103)	Healthy controls (n = 132)
Sex assigned at birth, n (%)
Male	69 (67)	48 (36.4)
Female	34 (33)	84 (63.6)
Age, mean ± standard deviation, years	63.44 ± 11	56.8 ± 16.87
Nationality, n (%)
Kuwaiti	49 (47.6)	88 (66.7)
Non-Kuwaiti	54 (52.4)	44 (33.3)
Cytological diagnosis, n (%)
Adenocarcinoma	101 (98)
Adenocarcinoma foamy cell variant	2 (2)
Tumor location, n (%)
Head	72 (70)
Body	14 (13.6)
Tail	13 (12.6)
Uncinate	4 (3.8)

Table 1. Demographic and Clinical Characteristics of Pancreatic Cancer and Healthy Control Cohorts

Criteria

Pancreatic cancer patients (n = 103)

Healthy controls (n = 132)

Sex assigned at birth, n (%)

Male

69 (67)

48 (36.4)

Female

34 (33)

84 (63.6)

Age, mean ± standard deviation, years

63.44 ± 11

56.8 ± 16.87

Nationality, n (%)

Kuwaiti

49 (47.6)

88 (66.7)

Non-Kuwaiti

54 (52.4)

44 (33.3)

Cytological diagnosis, n (%)

Adenocarcinoma

101 (98)

Adenocarcinoma foamy cell variant

2 (2)

Tumor location, n (%)

Head

72 (70)

Body

14 (13.6)

Tail

13 (12.6)

Uncinate

4 (3.8)

**Table 2.** Allele and Genotype Frequencies of Six Variants Assessed in Pancreatic Cancer and Healthy Control Samples
Variant	Pancreatic cancer (n = 103)	Healthy controls (n = 132)	P-value
All frequencies are shown as percent (%). ^aRisk alleles. *P < 0.05.
ABO rs505922 (C^a>T)
Allele (C/T) frequency	43.2/56.8	33.0/67.0	0.027*
Genotype
CC	21 (20.4)	12 (9.1)
CT	47 (45.6)	63 (47.7)
TT	35 (34.0)	57 (43.2)	0.037*
BCAR1 rs7190458 (G>A^a)
Allele (G/A) frequency	95.15/4.85	95.8/4.2	> 0.999
Genotype
GG	96 (93.2)	122 (92.4)
GA	4 (3.9)	9 (6.8)
AA	2 (1.9)	1 (0.8)	0.463
HNF1B rs4795218 (A>G^a)
Allele (A/G) frequency	30.1/69.9	23.5/76.5	0.114
Genotype
AA	11 (10.7)	11 (8.3)
AG	40 (38.8)	40 (30.3)
GG	52 (50.5)	81 (61.4)	0.248
LINC-PINT rs6971499 (T^a>C)
Allele (T/C) frequency	91.26/8.74	87.9/12.1	0.291
Genotype
TT	86 (83.5)	101 (76.5)
TC	16 (15.5)	30 (22.7)
CC	1 (1.0)	1 (0.8)	0.384
VDR rs2228570 (A>G)
Allele (A/G) frequency	30.6/69.4	21.2/78.8	0.024*
Genotype
AA	15 (14.5)	8 (6.1)
AG	33 (32.0)	40 (30.3)
GG	55 (53.4)	84 (63.6)	0.068
VDR rs731236 (A>G)
Allele (A/G) frequency	64.6/35.4	56.4/43.6	0.087
Genotype
AA	46 (44.7)	48 (36.4)
AG	41 (39.8)	53 (40.1)
GG	16 (15.5)	31 (23.5)	0.243

Table 2. Allele and Genotype Frequencies of Six Variants Assessed in Pancreatic Cancer and Healthy Control Samples

Variant

Pancreatic cancer (n = 103)

Healthy controls (n = 132)

P-value

All frequencies are shown as percent (%). ^aRisk alleles. *P < 0.05.

ABO rs505922 (C^a>T)

Allele (C/T) frequency

43.2/56.8

33.0/67.0

0.027*

Genotype

21 (20.4)

12 (9.1)

47 (45.6)

63 (47.7)

35 (34.0)

57 (43.2)

0.037*

BCAR1 rs7190458 (G>A^a)

Allele (G/A) frequency

95.15/4.85

95.8/4.2

> 0.999

Genotype

96 (93.2)

122 (92.4)

4 (3.9)

9 (6.8)

2 (1.9)

1 (0.8)

0.463

HNF1B rs4795218 (A>G^a)

Allele (A/G) frequency

30.1/69.9

23.5/76.5

0.114

Genotype

11 (10.7)

11 (8.3)

40 (38.8)

40 (30.3)

52 (50.5)

81 (61.4)

0.248

LINC-PINT rs6971499 (T^a>C)

Allele (T/C) frequency

91.26/8.74

87.9/12.1

0.291

Genotype

86 (83.5)

101 (76.5)

16 (15.5)

30 (22.7)

1 (1.0)

1 (0.8)

0.384

VDR rs2228570 (A>G)

Allele (A/G) frequency

30.6/69.4

21.2/78.8

0.024*

Genotype

15 (14.5)

8 (6.1)

33 (32.0)

40 (30.3)

55 (53.4)

84 (63.6)

0.068

VDR rs731236 (A>G)

Allele (A/G) frequency

64.6/35.4

56.4/43.6

0.087

Genotype

46 (44.7)

48 (36.4)

41 (39.8)

53 (40.1)

16 (15.5)

31 (23.5)

0.243

**Table 3.** Unweighted and Weighted PRS Models’ Test Performance Metrics With and Without Age and Sex Inclusion
Criteria	uwPRS	wPRS	uwPRS with sex and age	wPRS with sex and age
CI: confidence interval; PRS: polygenic risk score; uw: unweighted; w: weighted.
Nagelkerke R²	0.083	0.049	0.345	0.327
Accuracy (%)	62.8	60.7	69.7	70.5
Sensitivity (%)	32.4	27.5	64.7	67.6
Specificity (%)	86.4	86.4	73.5	72.7
Positive predictive value (%)	64.7	60.8	65.3	65.7
Negative predictive value (%)	62.3	60.6	72.9	74.4
Odds ratio (Expβ (95% CI))	1.54 (1.23 - 1.94)	3.35 (1.45 - 7.73)	1.52 (1.17 - 1.96)	3.42 (1.33 - 8.8)
P-value	< 0.001	0.005	0.001	0.011

Table 3. Unweighted and Weighted PRS Models’ Test Performance Metrics With and Without Age and Sex Inclusion

Criteria

uwPRS

wPRS

uwPRS with sex and age

wPRS with sex and age

CI: confidence interval; PRS: polygenic risk score; uw: unweighted; w: weighted.

Nagelkerke R²

0.083

0.049

0.345

0.327

Accuracy (%)

62.8

60.7

69.7

70.5

Sensitivity (%)

32.4

27.5

64.7

67.6

Specificity (%)

86.4

73.5

72.7

Positive predictive value (%)

64.7

60.8

65.3

65.7

Negative predictive value (%)

62.3

60.6

72.9

74.4

Odds ratio (Expβ (95% CI))

1.54 (1.23 - 1.94)

3.35 (1.45 - 7.73)

1.52 (1.17 - 1.96)

3.42 (1.33 - 8.8)

P-value

< 0.001

0.005

0.001

0.011