Insulin resistance and familial history of breast cancer

Objective

Insulin resistance has been linked to an increased risk of breast cancer. The main genes involved in low- to moderate-risk familial breast cancer remain to be identified. To test the hypothesis that there may be a genetic influence in insulin resistance, the present study analyzed the association of a familial history of breast cancer (low-tomoderate risk, defined as having a positive familial history of breast cancer) with insulin resistance.

Patients and method

We studied 846 healthy premenopausal women with no central obesity (NCO) (waist circumference < 88 cm) and with central obesity (CO) (waist circumference ≥ 88 cm), aged 18-50 years, body mass index 18-39.9, with and without a familial history of breast cancer. There were 494 women with NCO (108 with a positive familial history and 386 without) and 352 women with CO (103 with a positive familial history and 249 without).

Results

NCO women with a positive familial history for breast cancer showed a significantly higher frequency of insulin resistance (HOMA > 2.5 or postprandial insulin > 60 μUI/ml) [OR = 4.26 (95% CI, 2.04-8.83), p < 0.001], a higher frequency of low levels of high-density lipoprotein cholesterol (HDL-C) [OR = 3.27 (95% CI, 1.96-5.46), p < 0.001], a higher frequency of total cholesterol [OR = 1.78 (95% CI, 1.09-2.90), p = 0.01], a higher frequency of elevated total cholesterol, a higher frequency of elevated [OR = 3.23 (95% CI, 2.32-4.49, p < 0.001), a higher frequency of elevated triglycerides/HDL-C ratio [OR = 4.45 (95% CI, 1.80-10), p < 0.01] and higher frequency of neck circumference > 36.5 cm [OR = 4.25 (95% CI, 1.76-10.27), p < 0.01]. CO women with a positive familial history for breast cancer showed a significantly higher frequency of insulin resistance [(OR = 3.40 (95% CI, 2.08-5.55, p < 0.001)], a higher frequency of low levels of HDL-C (≤50 mg/dl) [OR = 2.51 (95% CI, 1.44-4.25), p < 0.01], a higher frequency of high triglycerides/HDL-C [OR = 2.25 (95% CI, 1.38-3.69), p < 0.01] and a higher frequency of neck circumference > 36.5 cm [OR = 2.08 (95% CI, 1.28-3.39), p = 0.01]. In both groups basal and postprandial glycemia and the frequency of acrochordons were significantly higher in women with a positive familial history for breast cancer.

Conclusions

We describe a previously unreported association in women between a family history of low-to-moderate risk of breast cancer and insulin resistance syndrome.

Objetivo

Analizar si la resistencia a la insulina (IR) se asocia a un riesgo incrementado de cáncer de mama (CM). No se ha encontrado hasta el momento los principales genes de CM familiar de bajo a moderado riesgo. Nuestra hipótesis es que se relacionan con la IR. Para evaluarla estudiamos la relación de la IR con la historia familiar de CM de bajo a moderado riesgo (AF+CM).

Pacientes y método

Se estudió a 846 mujeres sanas, premenopáusicas, con edades entre 18 y 50 años, IMC 18-39,9, sin (NOC) y con (OC) obesidad central (perímetro de cintura ≥ 88 cm), con (AF+CM) y sin (AF-CM) antecedentes familiares de CM. De las 494 mujeres NOC, 108 tenían AF+CM y 386 no los tenían; y de 352 mujeres OC, 103 tenían AF+CM y 249 no los tenían.

Resultados

Las mujeres NOC con AF+CM presentaron mayor frecuencia de IR (HOMA > 2,5 o insulina posprandial > 60 μUI/ml) (odds ratio [OR] = 4,26; intervalo de confianza [IC] del 95%, 2,04-8,83; p < 0,001), bajas cifras de colesterol de las lipoproteínas de alta densidad (cHDL ≤50 mg/dl) (OR = 3,27; IC del 95%, 1,96-5,46; p < 0,001), colesterol total elevado (≥ 200 mg/dl) (OR = 1,78; IC del 95%, 1,09-2,90; p = 0,01), triglicéridos (TG) elevados (≥ 150 mg/dl) (OR = 3,23; IC del 95%, 2,32-4,49; p < 0,001), elevada razón triglicéridos cHDL (> 3,2) (OR = 4,45; IC del 95%, 1,80-10,98; p < 0,01) y circunferencia de cuello > 36,5 cm (OR = 4,25; IC del 95%, 1,76-10,27; p < 0,01). Las mujeres OC con AF+CM presentaron mayor frecuencia de IR (OR = 3,40; IC del 95%, 2,08-5,55; p < 0,001), cHDL bajo (OR = 2,51; IC del 95%, 1,44-4,25; p < 0,01), TG/cHDL elevado (OR = 2,25; IC del 95%, 1,38-3,69; p < 0,01) y circunferencia de cuello > 36,5 cm (OR = 2,08; IC del 95%, 1,28-3,39; p = 0,01). En ambos grupos las glucemias basales y posprandiales y la frecuencia de acrocordones resultaron significativamente más elevadas en AF+CM.

Conclusiones

Describimos una asociación entre la historia familiar de CM de bajo y moderado riesgo y el síndrome de resistencia a la insulina hasta el momento no descrita.