A decade of letrozole: FACE

The variable penetrance of breast cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. The C to T transition in the 3′ untranslated region of the prohibitin (PHB) gene alters mRNA function and has been shown to be associated with an increased breast cancer risk among young North-American women who have one first-degree relative with breast cancer. To investigate whether the PHB 3′UTR polymorphism acts as a modifier of hereditary breast cancer risk we performed a case-control study among female BRCA1 mutation carriers, which included 258 cases and 258 controls who were unaffected by ovarian cancer, in situ breast carcinoma or any other type of cancer. Controls were matched to cases by year of birth and BRCA1 mutation (5382insC, 300 T > G, 4153delA). Genotyping analysis was performed using RFLP-PCR. Odds ratios (OR) were calculated using conditional and penalised univariable and multivariable logistic regression. Multivariable penalised logistic regression revealed CT (OR_adj, 2.03; 95% CI, 1.17–3.59) and combined CT + TT (OR_adj, 2.12; 95% CI, 1.23–3.70) genotypes as significant modifiers of breast cancer risk. Breast cancer risk did not differ between carriers of the 300 T > G and 5382insC mutation. Our results suggest that the PHB 3′UTR T allele increases the risk of breast cancer in patients who are already at increased risk of disease.