Subjects carrying the homozygous variant genotypes of -5G > A, -1A > C, c135G > A, c1296A > G or c2307T > G SNPs were at an increased risk for developing HSCR. Moreover, we also observed cumulative effects of these five polymorphisms on HSCR risk, demonstrating the haplotype composited with more HSCR-risk alleles rendered the hosts more susceptible to HSCR.