Variants in Wnt/beta-catenin Pathway Contributed to MM Risk, Varied by Race/Ethnicity

Researchers have identified genetic variations within the Wnt/beta-catenin pathway that may contribute to multiple myeloma (MM) susceptibility, with certain variations differing by race/ethnicity.

The study researchers first performed a discovery pathway analysis of 269 non-Hispanic White patients with MM and 272 controls. They looked at 171 variants selected from 26 core genes within the Wnt/beta-catenin pathway.

The researchers verified any significant candidate variant findings on an additional group of non-Hispanic White replication cases and performed external validation of the replicated findings using genotyping data from other institutions. Finally, the researchers examined the association of these variations with MM in non-Hispanic Black and Hispanic patients.

In the discovery population, seven variants were significantly associated with MM risk in non-Hispanic Whites. Two of these variants remained significant in the internal and external validation populations: LRP6:rs7966410 (odds ratio [OR]= 0.57; 95% CI, 0.38-0.88; P=9.90 x 10-3) and LRP6:rs7956971 (OR=0.64; 95% CI, 0.44-0.95; P=.027).

The variant CSNK1D:rs9901910 replicated among all three racial/ethnic groups, according to the researchers. There was a twofold to sixfold increased risk for MM depending on the group: non-Hispanic White, OR=2.40; non-Hispanic Black, OR=6.42; and Hispanic, 4.31.

“This  variant is  located within an enhancer region of  over  22  tissues, including those of  hematologic lineage,” the researchers noted. “Although CSNK1D has not been studied in MM, another member of the highly conserved casein kinase family, CK1α,  has  been shown to consistently sustain activation of the well-known oncogenic signaling cascade PI3K/AKT in MM.”

Inversely, BTRC:rs7916830 was associated with a 37% reduced risk of MM in the non-Hispanic White population and a 24% reduced risk for MM in the Hispanic population.

“Previous studies show the Wnt/beta-catenin pathway as a key player in cancer progression,” the researchers wrote. “Our results may provide further insight into  the  biology of  this  pathway as  well  as  its  role  in  MM development.”