Genome-wide association study of urinary cadmium levels in current smokers from the multiethnic cohort study

Background: Cadmium (Cd), classified as an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, is present in cigarette smoke. Recent studies have illustrated the potential role of genetics in influencing Cd biomarker levels. Methods: We conducted a genome-wide association study (GWAS) of urinary Cd levels in 1977 current smokers from the Multiethnic Cohort Study, comprising participants from five different racial and ethnic groups. Linear regression models were adjusted for age at urine collection, sex, self-reported race/ethnicity, and the top ten leading principal components. Results: Among the 11 710 497 single nucleotide polymorphisms (SNP) analyzed, no associations with urinary Cd reached genome-wide significance (P < 5.0 x 10(-8)). Notably, five variants demonstrated suggestive associations with urinary Cd levels (P < 1.0 x 10(-6)). Lead variants included: rs10097646 in the SCARA gene at 8q13.2 (P = 2.62 x 10(-7)); rs7444817 in the NIPBL gene at 5p13.2 (P = 3.10 x 10(-7)), rs830422 in the SPINK4 gene at 9q13.2 (P = 4.89 x 10(-7)); chrX:145489901 in the SLC9A7 gene at Xq121.1 (P = 5.38 x 10(-7)); and rs73074456 at 5p13.3 (P = 5.86 x 10(-7)). Conclusions: Our GWAS of urinary Cd levels in a diverse population of people who smoke, revealed suggestive associations with variants in SCARA5, NIPBL, SPINK4, SLC9A7, and 5p13.3. These findings underscore the potential role of genetic factors in understanding and mitigating the health risks associated with internal dose of carcinogens, particularly in the context of tobacco-related carcinogens.