As presented in Table 1 the matching between RT cases with and without SCC appeared unaffected by the overall selleck Rucaparib low response rate (39.1%). The representation of males dominated equally (~63%) in both groups. Mean ages at first transplantation (~45 years) and age of allograft (11�C12 years) did not differ significantly between the groups. No significant associations between skin phototypes, hair and eye color, on one side, and SCC on the other, were observed. Seven non-synonymous variants of MC1R were characterized by minor allele frequencies ranging from 1.6% (p.Asp84Glu) to 12.2% (p.Arg151Cys). The only variant apparently associated with risk of SCC specifically was the RHC allele p.Arg151Cys (OR = 1.99; CI: 1.05�C3.75) (Supplemental data; Table S1).
When adjusted for the concurrent presence of other MC1R variants or red hair, the basis for estimating the significance of p.Arg151Cys on an individual basis, diminished (not shown). Carriers of any variant or combination of variants implied a non-significant risk (OR = 1.85; CI: 0.92�C3.69), while carriers of two variants reached a significant association (OR = 2.36; CI: 1.08�C5.15) (Table 2). These estimates were unaffected when adjusted for eye, skin, or hair phenotypes (Supplemental data; Table S2). However, when stratified by phenotypic traits (Table 3), a significant elevation in SCC risk was observed in carriers of any MC1R variant combination with the darker skin phototype (SPT3) (OR = 3.94; CI: 1.37�C11.30). Against this background, it appeared sufficient to carry one of any variant combined with the wild type allele (OR = 3.
48; CI: 1.14�C10.60); not differing significantly from those being carriers of two MC1R variants of any type (OR = 4.62; CI: 1.47�C14.60) (Table 3 and Supplemental data; Table S3). When stratified by hair color, two of any of the MC1R variants indicated a higher risk of SCC in blond haired individuals (OR = 10.50; CI: 1.86�C59.27). Assessing the NRHC and RHC genotype groups individually revealed that only carriers of NRHC alleles reached significance (OR = 7.29; CI: 1.39�C38.20) (Table 3). All red-haired individuals (n = 16) were consistently positive for at least one RHC variant and negative for any NRHC variant; a representation observed evenly distributed between those with and without SCC (Supplemental data; Table S4).
When stratified by eye color, carriers of two of any MC1R variant and carriers of 1�C2 NRHC variants indicated an increased risk within the blue-eyed group of patients (OR = 2.80; CI: 1.15�C6.83, Carfilzomib and OR = 2.50; CI: 1.02�C6.16, respectively) (Table 3 and Supplemental data; Table S5). The presence of self-reported warts correlated with a relatively high SCC risk apparently independent of MC1R (Tables 1 and and3,3, and Supplemental data; Table S6). This was consistent with the observed independence between MC1R and warts (Supplemental data; Table S7).