Evaluation of polygenic risk score for risk prediction of gastric cancer

Table 1 Main characteristics of the included studies

Ref.	Population	Design	Group	Sample size	Sex, (%)	Age, (%)	SNPs (RA, OR)
Mao et al[19], 2017	Chinese	Case-control	GC, HC	2631, 4373	Male: 5100 (72.8%); female: 1904 (27.2%)	< 60 yr 3299 (52.9%); ≥ 60 yr 3705 (47.1%)	rs1514175 (A, 1.01), rs2815752 (A, 1.07), rs574367 (T, 1.11), rs12463617 (C, 1.05), rs1861411 (A, 1.02), rs6545814 (G, 1.05), rs10513801 (T, 1.17), rs2535633 (G, 0.98), rs16858082 (T, 0.96), rs261967 (C, 1.02), rs888789 (A, 0.99), rs6890814 (C, 0.99), rs4713766 (A, 1.05), rs9356744 (T, 1.03), rs9473924 (T, 0.98), rs17150703 (G, 1), rs4735692 (A, 1.02), rs11142387 (C, 1.06), rs1211166 (A, 1.02), rs11191580 (C, 0.92), rs10160804 (A, 0.99), rs11030104 (A, 1.02), rs11604680 (G, 0.97), rs2237892 (T, 1), rs671 (G, 1.12), rs897057 (C, 1.04), rs7989336 (A, 1.03), rs9568867 (A, 1.03), rs4776970 (A, 1.05), rs1558902 (A, 1.04), rs2531995 (T, 1.05), rs4788102 (A, 1.08), rs7503807 (A, 1), rs9299 (T, 0.9), rs591166 (A, 1.08), rs11671664 (G, 0.97), rs3810291 (A, 1.02)
Choi et al[20], 2020	European	Cohort	GC	272 cases in 400807 individuals	Male: 186372 (46.5%); female: 214435 (53.5%)	NR	rs2990223 (G, 1.27), rs10036575 (T, 1.23), rs2294008 (T, 1.21)
Jin et al[21], 2020	Chinese	Cohort	GC	Training set: 10254 cases and 10914 controls; validation set: 692 cases in 100220 individuals	Training set: NR; validation set: Male: 42862 (42.8%); female: 57358 (57.2%)	Training set: NR; validation set: < 60 yr 69805 (69.7%); ≥ 60 yr 30415 (30.3%); mean in case: 60.82 ± 9.33; mean in controls: 53.64 ± 11.00	NR
Qiu et al[22], 2020	Chinese	Case-control	GC, HC	1115, 1172	Male: 1615 (70.6%); female: 672 (29.4%)	< 60 yr 1162 (50.8%); ≥ 60 yr 1125 (49.2%)	rs13361707 (C, 1.47), rs2294008 (T, 1.19), rs4072037 (T, 1.38), rs3762272 (T, 1.21), rs2274223 (G, 1.35), rs80142782 (T, 1.36)
Wang et al[23], 2020	Chinese	Case-control	GC, HC	2631, 4373	Male: 5100 (72.8%); female: 1904 (27.2%)	< 60 yr 3299 (52.9%); ≥ 60 yr 3705 (47.1%)	rs1801133 (A, 1.02), rs2275565 (G, 1.01), rs4660306 (T, 1), rs1047891 (A, 1), rs9369898 (A, 1), rs548987 (C, 0.98), rs42648 (G, 1.01), rs1801222 (A, 0.99), rs12780845 (A, 1.01), rs7130284 (C, 1.01), rs2251468 (C, 1.03), rs154657 (A, 1.01), rs12921383 (C, 1.01), rs838133 (A, 1.02), rs234709 (C, 0.99)
Duan et al[24], 2021	Chinese	Case-control	GC, HC	544, 544	Male: 825 (75.8%); female: 263 (24.2%)	Mean in case: 57.80 ± 12.06; mean in controls: 57.02 ± 11.97	rs1859168 (C, 1.09), rs3815254 (A, 0.98), rs4784659 (C, 0.55), rs579501 (A, 0.71), rs77628730 (A, 1.26), rs6989575 (C, 1.03), rs7816475 (A, 1.19), rs6470502 (T, 0.51), rs1518338 (C, 1.08), rs2867837 (G, 0.95), rs12494960 (A, 2.62), rs74798803 (T, 0.97), rs7818137 (T, 1.2), rs550894 (T, 1.13), rs3825071 (A, 1.48), rs580933 (G, 0.98), rs7943779 (A, 1.54), rs911157 (T, 1.74), rs16981280 (C, 0.76), rs2273534 (C, 0.92), rs957313 (T, 1.04)
Ishikura et al[25], 2021	Japanese	Case-control	GC, HC	Training set: 696 cases and 1392 controls; validation set: 795 cases and 795 controls	Training set: Male: 1560 (74.7%); female: 528 (25.3%); validation set: Male: 1180 (74.2%); female: 410 (25.8%)	Training set: < 60 yr 1034 (49.5%); ≥ 60 yr 1054 (50.5%); validation set: < 60 yr 621 (39.1%); ≥ 60 yr 969 (60.9%)	rs4072037 (G, 1.35), rs2294008 (T, 0.62), rs7849280 (G, 0.24)
Park et al[26], 2021	Korean	Case-control	GC, HC	450, 1136	Male: 836 (52.7%); female: 750 (47.3%)	Mean in case: 55.4 ± 10.7; mean in control: 52.1 ± 8.5	rs2294008 (T, 1.2), rs6656150 (C, 0.8), rs8280142782 (C, 0.6), rs760077 (A, 0.8), rs140081212 (A, 0.8), rs4460629 (T, 0.8)

SNP: Single nucleotide polymorphism included in studies; GC: Gastric cancer group; HC: Healthy controls; NR: Not reported/Not retrieved; RA: Allele associated with gastric cancer; OR: Odds ratio.

Table 2 Development and evaluation of Polygenetic risk scores for predicting gastric cancer

Ref.	No. of SNPs included	SNP selection	PRS and related methods used to calculate it	AUC or OR (95%CI) of model with PRS	AUC or OR (95%CI) of model with PRS and Clinical risk factors	Difference	Clinical risk factors included
Mao et al[19], 2017	37	Significance level and linkage disequilibrium	Weighted PRS using weights derived from the same study	OR for the highest quartile respect to the lower quartile: 1.14 (1.01-1.29)	-	-	-
Choi et al[20], 2020	3	Significance level	Weighted PRS using weights derived from literature	AUC: 0.56 (0.53- 0.60); HR for the highest quintiles respect to the lower quintiles: 1.75 (1.18-2.59)	-	-	-
Jin et al[21], 2020	112	Significance level	Weighted PRS using weights derived from the same study	HR for the highest quintiles respect to the lower quintiles: 2.08 (1.61-2.69)	HR for participants with a high genetic risk and an unfavorable lifestyle respect to those with a low genetic risk and a favorable lifestyle 5.14 (2.04–12.93)	-	Smoking, alcohol consumption, consumption of preserved foods, intake of fresh fruit and vegetables
Qiu et al[22], 2020	6	Significance level and validated to be associated with gastric cancer risk	Weighted PRS using weights derived from the same study	AUC 0.653	AUC 0.684	0.031	BMI
Wang et al[23], 2020	15	Significance level	Weighted PRS using weights derived from literature	OR for the highest quartile respect to the lower quartile: 1.19 (1.04–1.37)	-	-	-
Duan et al[24], 2021	21	Prediction functions through bioinformatics tools	Weighted PRS using weights derived from the same study	AUC 0.737 (0.71-0.76); OR for the highest 10% respect to the 40-60%: 5.75 (3.09-10.70)	AUC for PRS + Hp infection: 0.752 (0.690-0.814); AUC for PRS + family history of tumor: 0.773 (0.702-0.843)	PRS + Hp infection: 0.014; PRS + family history of tumor: 0.036	Hp infection, family history, smoking, alcohol consumption
Ishikura et al[25], 2021	3	Significance level	Weighted PRS using weights derived from the same study	AUC for training set: 0.6287 (0.6039–0.6530); AUC for validation set: 0.5673 (0.5391–0.5960)	AUC for training set: 0.7677 (0.7465–0.7890); AUC for validation set: 0.7823 (0.7694–0.8140)	Training set: 0.139; validation set: 0.215	Smoking, alcohol consumption, fruit and vegetable intake, and ABCD classification
Park et al[26], 2021	6	Significance level	Weighted PRS using weights derived from literature	AUC: 0.565 (0.535–0.596); OR for the highest tertile respect to the lower tertile: 2.03 (1.51–2.72)	AUC: 0.607 (0.576–0.638); OR for the highest tertile respect to the lower tertile: 2.53 (1.92–3.34)	0.042	A sex-specific prediction model

SNP: Single nucleotide polymorphism; PRS: Polygenic risk score; AUC: Area under the curve; OR: Odds ratio; HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; Hp: Helicobacter pylori; ABCD classification: Helicobacter pylori infection-related factor.