Genetic polymorphisms in breast cancer: Age-related and ethnic differences between Asian and Western populations

Dear Editor,

Breast cancer genetic polymorphisms differ meaningfully by age at diagnosis and ethnicity, with implications for targeted screening [Table 1].

Women who develop cancer before turning 50-years-old show the highest occurrence of germline BRCA1, BRCA2 and TP53 mutations in various demographic groups. Asian patients who are ≤35-years-old show TP53 mutations at a rate of 5-6%.^[1-3] The diagnosis of breast cancer after age 50 shows a connection to oestrogen metabolism gene variations because CYP17 T-34C (rs743572) raises breast cancer risk in postmenopausal women, and MPO G463A increases breast cancer risk among Caucasian women after menopause.^[4,5]

BRCA2 mutations occur more often in Asian populations, but BRCA1 mutations appear more frequently among Caucasian populations. The total BRCA1/2 mutation rate remains similar across populations (2%–4%); however, Western risk models fail to detect these mutations in Asian American populations.^[6] The CYP1B1 Leu432Val and CYP1A2*1F genetic variants lead to higher breast cancer risk before menopause in Japanese and Chinese women.^[4] The CXCL12 rs1801157 genetic variant produces opposite risk effects.^[7] Elevated somatic TP53 mutations in young Asian ER (oestrogen receptor) + tumours suggest aggressive early-onset biology distinct from Western patterns.^[2,3]

These findings highlight the need for ethnicity- and age-specific risk models, particularly TP53 screening in young Asian women. Larger, ethnically diverse studies are needed for confirmation.