علاقة تغايرات جين TLR7 مع بعض المؤشرات الكيموحيوية بين النساء المصابات بسرطان الثدي

Association of TLR7 Gene Variants with Some Biochemical Markers among Breast Cancer Women

Abstract

The present study as a Case-Control Study was carried out in the Department of Clinical Laboratories / College of Applied Medical Sciences / University of Kerbala during the period from November 2022 to May 2024. The study aimed to shed light on the association between the variant of the TLR7 gene and serum level of some biochemical markers (CA15-3, CEA, CA125, and CA27-29) in breast cancer patients from Iraqi women. 100 women volunteers enlisted, 50 women with the breast cancer , in contrast 50 women included apparently healthy were enrolled in this study, with an age range of (29-75) years at the time of the investigation.
The blood samples were drawn from volunteers were recruited from AL-Imam AL-Hussein Center for Oncology and Hematology in Karbala city / Iraq , the ethical consent was signed by each volunteer. The study was a population genetic study, carried out on two group samples. The variants of the TLR7 gene were investigated by the Sanger sequencing method. The serum levels of) CA15-3, CEA, CA125, and CA27-29( were measured by enzyme linked immunosorbent assay (ELISA) technique. The statistical analysis displayed statistically significant differences when the serum levels of the four tumor markers namely )CEA, CA125, CA15-3, and CA27-29( were compared between control and patient groups (p<0.001).
The genetic analysis of the results of the 20 samples (selected from patient samples) showed different types of variants in the TLR7 gene. The number of variants present in the samples was different from one sample to another, the all 20 samples displayed multiple variants in their exon4 region sequences , while 6 out of 20 samples demonstrate double variants and the rest 14 samples displayed multiple variants in intron2 region sequences.
The detected variants were divided into two groups, previously registered variants (4 variants, 1 exon4 and 3 intron2), and novel non-registered variants (13 variants, 8 exon4 and 5 intron2).
The previously registered variants [12888260 G/A] was detected in Exon4 region in 10 out of 20 samples , while variants [12871738 A\G, 12871850 A\C, and 12871888 T\A] were detected in Intron2 region in 18 out of 20 samples. The novel non-registered variants [12888227 T\G, 12888234 T\G, 12888246 T\G, 12888294 A\G, 12888276 A\T, 12888269 G\A, 12888351 A\G, and 12888221 A\C] were detected in Exon4 region in 12 out of 20 samples, while variants [12871741 A\T, 12871749 G\C, 12871759 T\G, 12871764 A\G, and 12871768 G\C] were detected in Intron2 region in 17 out of 20 samples.
The effects of TLR7 gene variants on study parameters )CA15-3, CEA, CA125, and CA27-29( were investigated and the results showed that the variant [12871749 G/C] of the intron2 region was moderately negatively and statistically significantly correlated with the CEA tumor marker serum levels (point biserial correlation coefficient = -0.396 , p value = 0.03). Furthermore, the statistical analysis showed a statistically significant correlation (p value = 0.015) between the variant [12888221 A/C] of the exon4 region and the CA125 tumor marker serum value, the interaction was of an intermediate correlation (point biserial correlation coefficient = -0.442).
The variant [12871764 A/G] of the intron2 region was moderately associated with the CA15-3 tumor marker levels (point biserial correlation coefficient = -0.385) and the two variables were statistically significantly associated (p value = 0.036).

The results of Exon4 region displayed significant differences between the same groups in the level of CEA (p value = 0.015), while the result displayed non-significant differences between the two groups divided according to number of variants (<6 and >6 variants) in the level of CA125, CA15-3, and CA27-29 with a p value 0.44, 0.96, and 0.48 respectively.
The statistical analysis indicated non-significant differences between new and mixed variants in the level of CEA, CA125, and CA27-29 with a p value 0.76, 0.32, and 0.428 respectively. While the result of CA15-3 displayed significant differences between new and mixed variants where )p value = 0.02( in Exon4 region.