がんリスク遺伝子BRCA1/2と4種のがんとの関連を同定－甲状腺・膀胱・頭頸部・皮膚がんの個別化医療の発展の可能性－

2026-04-15

2026-04-15 理化学研究所,東京大学医科学研究所,秋田大学,日本医科大学,愛知県がんセンター

理化学研究所、東京大学医科学研究所、秋田大学、日本医科大学、愛知県がんセンターの共同研究は、がんリスク遺伝子BRCA1/2が新たに4種のがん（甲状腺・膀胱・頭頸部・皮膚がん）の発症リスクとも関連することを明らかにした。約4万人の日本人データを用いたゲノム解析により、BRCA1は甲状腺がん、BRCA2は膀胱・頭頸部・皮膚がんと有意な関連を示した。特に膀胱がんでは女性のリスク上昇が顕著であった。これにより、従来の乳がん・卵巣がんなどに加え、より広範ながんに対する個別化医療やPARP阻害薬の適用拡大の可能性が示された。

BRCA1/2遺伝子における病的バリアント保持者の85歳までの推定累積リスクの概要図

＜関連情報＞

BRCA1およびBRCA2の病原性変異は、4種類の比較的まれな癌のリスクを高める BRCA1 and BRCA2 pathogenic variants increase the risk of four less common cancer types

H. Sasagawa ∙ M. Endo ∙ Y. Iwasaki ∙ … ∙ A.B. Spurdle ∙ T. Habuchi ∙ Y. Momozawa
ESMO Open Published:April 7, 2026
DOI:https://doi.org/10.1016/j.esmoop.2026.106900

Highlights

We analyzed BRCA1 and BRCA2 pathogenic variants for nine less common cancer types.
BRCA1 pathogenic variants increase the risk of thyroid cancer.
BRCA2 pathogenic variants increase the risk of bladder, head and neck, and skin cancers.
The impact of pathogenic variants in bladder cancer was especially higher in females than in males.
This study suggests the potential for expanding and refining personalized medicine.

Abstract

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 (P_{heterogeneity} = 2.15 × 10⁻⁴; I² = 92.70%).