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Height and body mass index as modifiers of breast cancer risk in BRCA1/2 mutation carriers: A Mendelian randomization study

Journal of the National Cancer Institute Oct 18, 2018

Qian F, et al. - Experts evaluated if the breast cancer risk in BRCA1/2 mutation carriers is modified by height or body mass index (BMI). Findings suggested that in these patients there is a link between height with overall breast cancer risk and between BMI and premenopausal breast cancer. Findings suggested that cancer management may be improved by the incorporation of height and BMI, particularly genetic score, into risk assessment.

Methods

  • Using Mendelian randomization approaches, researchers evaluated the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14,676 BRCA1 and 7912 BRCA2 mutation carriers, including 11,451 cases of breast cancer.
  • They created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants.
  • They examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models.
  • They noted all statistical tests to be two-sided.

Results

  • Findings suggested a positive association of the observed height with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P= 1.17).
  • As per data, there is a positive association of height genetic score with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P= .47).
  • There was an inverse association of the observed BMI with breast cancer risk (per 5 kg/m 2increase, HR = 0.94, 95% CI = 0.90 to 0.98; P=.007).
  • Experts noted an inverse association of BMI genetic score with breast cancer risk (per 5kg/m2increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P=.02).
  • BMI was mainly associated and premenopausal breast cancer.
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