BRCA1 and BRCA2 pathogenic variants increase the risk of four less common cancer types.

BACKGROUND

Previous family-based and case-control studies have expanded the cancer risk profile associated with pathogenic variants in BRCA1 and BRCA2, providing the potential for expanding personalized medicine. Less common cancer types may benefit greatly from such expansion of genetic evidence because of their limited treatments and poor prognoses.

METHODS

We conducted a case-control analysis of 3489 patients with nine less common cancer types (bladder, bone, brain, head and neck, sarcoma, skin, testis, thyroid, or ureteral cancer) and 38 842 controls without cancer to estimate the risk associated with BRCA1 and BRCA2 pathogenic variants of nine less common cancer types.

RESULTS

We identified 105 pathogenic variants among 994 germline variants. We observed four significant associations: BRCA1 with thyroid cancer [odds ratio (OR) 5.25, 95% confidence interval (CI) 2.06-13.38]; BRCA2 with bladder (OR 4.67, 95% CI 2.57-8.47), head and neck (OR 3.89, 95% CI 2.01-7.53), and skin cancers (OR 6.13, 95% CI 2.47-15.24). For bladder cancer, the impact of BRCA2 pathogenic variants was greater in females than in males (Pheterogeneity = 2.15 × 10-4; I2 = 92.70%).

CONCLUSIONS

These results provide evidence to inform more precise personalized medical options for individuals with BRCA1 or BRCA2 pathogenic variants.