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Background Leptin, a 16 kDa polypeptide hormone, implicated in various physiological processes, exerts its action through the leptin receptor, a member of the class I cytokine receptor family. Both leptin and leptin receptor have recently been implicated in processes leading to breast cancer initiation and progression in animal models and humans. An A to G transition mutation in codon 223 in exon 6 of the leptin receptor gene, resulting in glutamine to arginine substitution (Gln223Arg), lies within the first of two putative leptin-binding regions and may be associated with impaired signaling capacity of the leptin receptor. This study was designed to assess the role of this polymorphism in breast cancer susceptibility in Nigerian women. Methods We utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to evaluate the association between the Gln223Arg polymorphism of the leptin receptor gene and breast risk in Nigeria in a case control study involving 209 women with breast cancer and 209 controls without the disease. Study participants were recruited from surgical outpatient clinics and surgical wards of four University Teaching Hospitals located in Midwestern and southeastern Nigeria between September 2002 and April 2004. Results Premenopausal women carrying at least one LEPR 223Arg allele were at a modestly increased risk of breast cancer after adjusting for confounders (OR = 1.8, 95% confidence interval [CI] 1.0–3.2, p = 0.07). There was no association with postmenopausal breast cancer risk (OR = 0.9, 95% CI 0.4–1.8, p = 0.68). Conclusion Our results suggest that the LEPR Gln223Arg polymorphism in the extracellular domain of the LEPR receptor gene is associated with a modestly increased risk of premenopausal breast cancer in Nigerian women.

Background The leptin receptor gene (LEPR) polymorphism Q223R is one of the most common in the general population, and is thought to be associated with an impaired signaling capacity of the leptin receptor and with higher mean circulating levels of leptin. Leptin is a hormone primarily produced in adipose tissue. Increased levels of leptin have been positively correlated with obesity. We have determined the frequency of the leptin receptor polymorphism (LEPR Q223R) in healthy populations from various ethnic groups, and compared plasma leptin levels across the LEPR Q223R polymorphism in healthy African-Caribbean and Caucasian women. Results The study population consists of 1,418 healthy subjects from various ethnic groups. The LEPR Q223R homozygous variant was observed overall in 19% of subjects (n = 1,418), with significant differences based on self reported ethnicity: the proportion of subjects with the homozygous variant was lower in Caucasians (14%, n = 883) than in African-Caribbean (n = 194), African-American (n = 36) and Asian/other ethnic groups (n = 26), (35%, 33% and 34.6% respectively); the frequency in Africans (20%), was similar to the overall study population. The mean ± standard deviation (SD), circulating leptin levels for African-Caribbean women was 44.7 ± 31.4 ng/ml, while for Caucasian women the mean was 42.4 ± 34.8 ng/ml. Adjusted circulating leptin levels in post-menopausal Caucasian women who were LEPR Q223R homozygous variant were marginally statistically significantly higher than in women with the wild-type genotype (p = 0.098). No significant differences in leptin levels by genotype were observed for African-Caribbean women, (heterozygous: p = 0.765, homozygous variant: p = 0.485). Conclusion These findings suggest an association between mean circulating leptin levels and the LEPR Q223R genotype among post-menopausal Caucasian women.

Background An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens. Methods This study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method. Results The average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone was measured in urine. However, the 2/16 ratio was similar in urine and breast tissue. Women carrying the variant CYP1B1 genotype (Leu/Val and Val/Val) showed significantly lower overall estrogen metabolite, estrogen, and 16-hydroxylation pathway levels in breast tissue in comparison to women carrying the wild type genotype. No effect of the CYP1B1 polymorphism was observed in urinary metabolites. Conclusions The urinary 2/16 ratio seems a good approximation of the ratio observed in breast tissue. Metabolic genes may have an important role in the estrogen metabolism locally in tissues where the gene is expressed, a role that is not readily observable when urinary measurements are performed.