Evaluation of Leptin Receptor Q223R (rs1137101) Polymorphism Based on Histopathological and Body Mass Index Characteristics in Iranian Females with Breast Cancer

Abstract

Background: The mechanism of the relationship between obesity and the risk of breast cancer is still unknown. Objectives: The current study aimed at evaluating the relationship between the leptin receptor Q223R (Gln/Arg) polymorphism, body mass index (BMI), and histopathological changes in patients with breast cancer. Methods: A total of 158 patients with breast cancer and 158 healthy subjects within the same age range were recruited. After taking blood sample, DNAs were extracted using the salting-out method. Then, the polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping. The histopathological characteristics were determined by the immunohistochemistry technique. Results: Investigation of the relationship between BMI and alleles showed that the G (Arg) mutant elevated the risk of affection by 2.294 times, while the allele A had a descending effect by 0.375 times. The comparison of genotypes with histopathological changes showed a significant relationship between the GG (Arg/Arg) genotype and higher levels of progesterone receptor expression (P = 0.005), invasive type of cancer (P = 0.010), and stage of the disease (P = 0.003). Conclusions: People with higher BMI who also carried G (Arg) mutant of Q223R polymorphism were more prone to breast cancer. Also, tissue changes in the ones carrying this allele were more than those harboring the wild-type A (Gln) allele.

Correlation of Q223R and K109R polymorphisms in leptin receptor gene with susceptibility of breast cancer: A systematic review and meta-analysis

“…Another study 34 was excluded because it was review article, one studies 37 were excluded because it was a case-only study, two studies 38,39 were excluded they were not case-control studies. Ultimately, 21 studies 8–28 were included in this meta-analysis. Their characteristics and genotype distributions are summarized in Table 1.…”

“…Next, meta-analysis of data from 1457 Asian cases and 1762 Asian controls in nine studies 8,12,17–22,25 also showed no evidence of a significant association between the Q223R polymorphism and BC risk (Table 2): allelic model, OR = 0.79, 95% CI = 0.54-1.16, p = 0.24; recessive model, OR = 0.75, 95% CI = 0.51-1.09, p = 0.13; dominant model, OR = 1.33, 95% CI = 0.58-3.03, p = 0.50; homozygous model, OR = 0.66, 95% CI = 0.26-1.63, p = 0.36; heterozygous model, OR = 0.92, 95% CI = 0.42-2.01, p = 0.83.…”

“…Twenty studies [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] focused on Q223R and eight 8,13,16,21-23,27,28 on K109R. The distribution of genotypes in controls was consistent with the Hardy-Weinberg equilibrium in all but five studies.…”

“…The distribution of genotypes in controls was consistent with the Hardy-Weinberg equilibrium in all but five studies. 12,18,21,22,25 The mean Newcastle-Ottawa score for the 12 studies was 6.60 (range, 5-8). Thus the overall quality of the included studies was adequate.…”

“…7 Nevertheless, their potential associations with BC risk have not been fully investigated. Among them, Q223R (rs1137101) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] and K109R (rs1137100) 8,13,16,[21][22][23]27,28 polymorphisms for BC have been most commonly studied. However, the results were inconsistent.…”