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

This study's aim was to clarify the regulatory roles of the <i>MKI67</i> rs11016073 and <i>APOB</i> 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 <i>APOB</i> non-GG and <i>MKI67</i> non-AA genotypes exhibited the lowest breast cancer risk at the highest Pb levels (Q4), whereas carriers of <i>APOB</i> GG and <i>MKI67</i> 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 <i>MKI67</i> and <i>APOB</i> genotyping may improve risk stratification and interpretation of non-linear Pb-cancer associations.