Our results suggest that non-O blood group was significantly associated with a decreased risk of non-melanoma skin cancer overall. Compared to participants with blood group O, participants with non-O blood group had a 14% decreased risk of developing SCC and a 4% decreased risk of developing BCC. The decreased risk of melanoma for non-O blood group (A, AB, and B combined or separately) was not statistically significant.
There are several plausible hypotheses for the observed association between ABO blood groups and skin cancer risk. One possible explanation is that ABO blood group may be directly associated with skin cancer through certain biological mechanisms. Blood group antigens are expressed on the surface of many epithelial cells, including skin cells 
. One study evaluating normal penile skin compared to squamous cell carcinoma showed less A antigen expression in SCC compared to normal skin 
, which is consistent with our finding that A blood type was less common in SCC cases. Other studies have shown that ABO blood group antigen expression in tumors is associated with metastasis and prognosis 
. Hence, several plausible mechanisms, including inflammation, immunosurveillance for malignant cells, intercellular adhesion, and membrane signaling have been proposed to explain the observed association between ABO blood groups and cancer risk 
. In addition, the ABO
gene on chromosome 9q34 encodes glycotransferases to form the ABO blood group antigens 
. Differential expression of blood group antigens on epithelial cells may influence tumorigenesis through altered glycosyltransferase specificity 
. An alternative explanation is that ABO blood group may be indirectly associated with skin cancer. It is possible that the ABO gene was in linkage disequilibrium with other genes involved in skin carcinogenesis.
Many previous studies have reported an association between ABO blood group and the risk of various cancers, especially epithelial cancers. One study using the same two cohorts reported an association between ABO blood type and the risk of developing pancreatic cancer (P
.004; log-rank test). In this study, compared with participants with blood group O, those with blood groups A, AB, or B were more likely to develop pancreatic cancer (adjusted HRs for incident pancreatic cancer were1.32, 1.51, and 1.72, respectively) 
. Another NHS-based study suggested the presence of the B antigen was positively associated with the risk of epithelial ovarian cancer, while blood group A was not associated with risk (manuscript in submission).
To date, ours is the first prospective cohort study investigating the relationship between ABO blood group and the risk of skin cancers. Only one previous case-control study conducted in Turkey examined the relationship between ABO blood groups and skin cancers 
. The study recruited 98 histologically confirmed skin cancer cases (23 SCC, 42 BCC, and 33 in situ
SCC) and 419 healthy controls. Skin cancer cases were more likely than controls to be in blood groups A, AB, and B than O (odds ratios ranged from 1.50 to 3.77), but these results were not statistically significant. There are several possible reasons for the observed differences between our results and the results of the previous case-control study. First, our participants are white residing in the US, while the case-control study population was from Mersin in Turkey. The association between ABO blood group and the risk of skin cancer may vary among different races or ethnicities. Second, results from the previous case-control study were based on a relatively small sample size, and confidence intervals were wide.
One of the major strengths of our study is its prospective design. We performed a secondary analysis using the ABO blood group assessment data (1996) as the baseline for the follow-up to confirm our primary analysis results. Another strength of our study is the large study population and the high follow-up rate. Also, the availability of many risk factor covariates allowed us to assess the association while controlling for potential confounding within each ABO blood group. The high concordance rate between reported blood type and serologic testing in a subset of our study population suggests the validity of self-reported blood type.
In conclusion, data from two large cohort studies demonstrated the association between non-O blood group and a decreased risk of each type of skin cancer. The association was statistically significant for non-melanoma skin cancer. The opposing association of the non-O blood group with skin cancer compared to that with pancreatic, gastric, and ovarian cancers suggests unique carcinogenic mechanisms of skin cancer. We considered the analysis exploratory and further investigation is warranted to confirm this finding and to illuminate skin carcinogenesis.