OBJECTIVEThe aim of this study was to investigate the relationship of the mutations of leptin receptor gene exon 4, exon 6, exon9, and exon20 with the tumorigenesis of breast cancer.

METHODSGenomic DNA was extracted from breast cancer tissues of 155 patients, benign lesions of 56 patients and normal tissues and blood samples from 100 health control subjects. The leptin receptor genes were assayed with polymerase chain reaction (PCR) amplification and direct sequence analysis.

RESULTSNucleotide substitutions no mutations were found at exon 4, and nucleotide substitutions occurred at codon 1029 in exon 9, no significant difference among the three groups (P = 0.574). The nucleotide substitutions at codon 668 in exon 6 resulted in Gln223Arg polymorphisms. The occurring frequencies of GG, GA, AA in breast cancer, breast benign lesions tissues and health tissues control group were 70.9% and 17.4%, 12.3%; 80.4%, 14.3% and 5.4%; and 81.0%, 16.0%, and 3.0%, respectively. Alleles of G and A in the three groups were 79.1% and 20.8%, 87.5% and 12.5%, and 89.0% and 11.0%, respectively. Compared the Gln223Arg genotype with the three allele groups, there were significant differences (χ(2) = 16.11, P < 0.005 and χ(2) = 11.41, P < 0.01), respectively. The nucleotide substitutions at codon 3057 in exon 20 resulted in Pro1019Pro polymorphisms. The occurrence frequencies of GG, GA, AA in the breast cancer, benign disease and health control groups were 11.6%, 30.3% and 56.1%; 32.1%, 44.0% and 28.5%; and 32.0%, 45.0% And 23.0%, respectively. Alleles of G and A in the three groups were 26.8% and 73.2%, 51.8% and 48.2%, and 54.5% and 45.5%, respectively. There are significant differences among the three groups (χ(2) = 6.56, P < 0.03 and χ(2) = 5.45, P < 0.05), respectively. Nucleotide substitutions occurred at relatively high frequencies at exon 6 and exon 20 in obese and overweight breast cancer patients compared with those in normal weight breast cancer patients, there were significant differences (P < 0.05 and P < 0.01).

CONCLUSIONSOur findings show that there is no relationship between the variations of leptin receptor gene exon 9 and tumorigenesis of breast cancer. The variation rate of leptin receptor gene exon 6 and exon 20 are significantly increased in the obese and overweight breast cancer patients.