Evidence for Genotype-Specific Optimal Blood Lead Levels for Cancer Risk: MKI67 rs11016073 and APOB rs1367117 in a...

This study's aim was to clarify the regulatory roles of the MKI67 rs11016073 and APOB rs1367117 polymorphisms in the relationship between blood Pb levels and cancer risk. Blood Pb concentrations were measured using inductively coupled plasma mass spectrometry, and genotyping was performed by real-time PCR with TaqMan probes. Cancer incidence was assessed during a mean follow-up of six years and two months. During follow-up, 210 incident cancers were diagnosed among 2782 women. Pb exposure was categorized into quartiles (Q1: <9.44 µg/L; Q2: 9.44-12.58 µg/L; Q3: 12.59-17.16 µg/L; Q4: >17.16 µg µg/L). The association between Pb levels and cancer risk was strongly genotype dependent. Women carrying APOB non-GG and MKI67 non-AA genotypes exhibited the lowest breast cancer risk at the highest Pb levels (Q4), whereas carriers of APOB GG and MKI67 AA showed the lowest risk at the lowest Pb levels (Q1). Age-stratified analyses further demonstrated genotype-specific differences in optimal Pb exposure ranges, particularly for breast cancer. Cancer risk associated with Pb exposure is not uniform but depends on genetic background. These findings identify genotype-specific optimal blood Pb levels and suggest that incorporation of MKI67 and APOB genotyping may improve risk stratification and interpretation of non-linear Pb-cancer associations.