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Insulin resistance and familial history of breast cancer

Abstract:

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-to-moderate 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.