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. 2020 Oct 1;21(10):3115-3123.
doi: 10.31557/APJCP.2020.21.10.3115.

Evaluating the Possible Association between PD-1 (Rs11568821, Rs2227981, Rs2227982) and PD-L1 (Rs4143815, Rs2890658) Polymorphisms and Susceptibility to Breast Cancer in a Sample of Southeast Iranian Women

Shima Karami  1 , Hedieh Sattarifard  1   2 , Mohammad Kiumarsi  2 , Sahel Sarabandi  1 , Mohsen Taheri  3 , Mohammad Hashemi  1 , Gholamreza Bahari  1   4 , Saeid Ghavami  2   5   6
Affiliations

Evaluating the Possible Association between PD-1 (Rs11568821, Rs2227981, Rs2227982) and PD-L1 (Rs4143815, Rs2890658) Polymorphisms and Susceptibility to Breast Cancer in a Sample of Southeast Iranian Women

Shima Karami et al. Asian Pac J Cancer Prev. .

Abstract

Introduction: Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) play a critical role as a regulator of immune-system cells, including T cell, natural killer T (NKT), monocytes, dendritic cells (DC), and B cells.

Objective: This study aimed to find a possible association between PD-1 (rs11568821, rs2227981, rs2227982), and PD-L1 (rs4143815, rs2890658) variants and Breast Cancer (BC) risk in a sample of southeast Iranian women.

Method: The case-control study consisted of 520 individuals, including 260 histologically confirmed BC patients and 260 non-cancer age-matching healthy women as the control group. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS-PCR) methods were used for genotyping of PD-1 (rs11568821, rs2227981, rs2227982), and PD-L1 (rs4143815, rs2890658) polymorphisms.

Results and conclusion: Our findings indicated that the PD-L1 rs4143815 (G/C) variant meaningfully reduced the risk of BC. However, the PD-L1 rs2890658 variant increased the BC risk in the AC genotype as well as the A allele. Furthermore, we could not find a meaningful association between PD-1 rs11568821, PD-1 rs2227981, PD-1 rs2227982, and BC. Our team examined the possible association between variants and clinicopathological characteristics, including age, size of tumour, lymph node, histology, grade of tumour, estrogen and progesterone receptors status as well as human growth factor receptor 2 (HER2). Our findings demonstrated that PD-L1 rs4143815, PD-L1 rs2890658, PD-1 rs2227982 had a significant association with age. Additionally, we found a significant relation between PD-1 rs2227982 variant and tumour size. Statistical analyzes of PD-1 rs2227981 and PD-1 rs11568821 variants showed a meaningful relation between tumour grade and tumour stage (p=0.006), respectively.<br />.

Keywords: Apoptosis; PD-1; PD-L1; Polymorphism; cancer.

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Figures

Figure 1
Figure 1
(1A) electrophoresis pattern of the PCR-RFLP method for the detection of PD-1rs11568821(G/A) polymorphism. M: DNA marker; Lanes 1 and 4: GA; Lanes 2 and 3: GG (1B): Photograph of electrophoresis pattern of the PCR-RFLP method for detection of PD-1 rs2227981(C/T) polymorphism. M, DNA marker; Lanes 1 and 6, CT; Lanes 2 and 5, CC; lanes 3 and 4, TT
Figure 2
Figure 2
(2A). Electrophoresis pattern of the PCR-RFLP method for the detection of PD-1rs2227982(C/T) polymorphism. M: DNA marker; Lanes 1 and 6: CT; Lanes 2 and 5: CC; lanes 3 and 4: TT. (2B) electrophoresis pattern of the PCR-RFLP method for the detection of PD-L1rs2890658(C/A) polymorphism. M: DNA marker; Lanes 1 and 6: CA; Lanes 2 and 5: AA; lanes 3 and 4: CC
Figure 3
Figure 3
Electrophoresis Pattern of the T-ARMS Method for the Detection of PD-L1rs4143815(G/C) Polymorphism. M, DNA marker; Lanes 1 and 6, GC; Lanes 2 and 5, CC; lanes 3 and 4, GG
Figure 4
Figure 4
Sequencing of PD-L1 rs4143815
See this image and copyright information in PMC

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