Etiology of familial aggregation in melanoma and squamous cell carcinoma of the skin.
BACKGROUND
Melanoma and squamous cell carcinoma of the skin (SCC) have been previously shown to coaggregate in families. To shed light on the etiology, we estimated the relative contributions of genetic and environmental factors on the occurrence of each disease, in addition to their influence on coaggregation of the two diseases. Because the malignancies are dependent on UV radiation, we did separate analyses for sun-covered and sun-exposed sites.


METHODS
Our Swedish population-based data included 11 million individuals in 3 million families. We used an extended generalized linear mixed model to estimate the genetic and environmental contribution.


RESULTS
In melanoma, the genetic contribution was 18% [95% confidence interval (95% CI), 13-22%] in the all-sites analysis, whereas the family-shared contribution was slightly higher in the sun-covered compared with sun-exposed sites analysis. SCC revealed very similar estimates in all analyses for both the genetic effects estimated to 8% (95% CI, 4-12%) and family-shared environmental factors at 18% (95% CI, 16-19%), respectively. In the coaggregation analysis, genetic and family-shared environmental components were estimated at 47% (95% CI, 43-51%) and 36% (95% CI, 33-39%), respectively.


CONCLUSIONS
Genetic factors are important in familial aggregation of melanoma and the higher sun-covered compared with sun-exposed site estimate of family-shared environment may convey benefit from cautious sunbathing. In SCC, we observed the highest contribution of family-shared environmental effects in cancer to date, implicating the importance of familial habits. Moreover, we elucidate the potential involvement of genetic variability in the familial coaggregation of melanoma and SCC.
Lindström
Linda S
LS
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, P.O. Box 281, Stockholm 17177, Sweden. Linda.Lindstrom@ki.se
Yip
Benjamin
B
Lichtenstein
Paul
P
Pawitan
Yudi
Y
Czene
Kamila
K
D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D004777:Environment; D004781:Environmental Exposure; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D008957:Models, Genetic; D009679:Nuclear Family; D011159:Population Surveillance; D012042:Registries; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D013472:Sunlight / Q000009:adverse effects; D013548:Sweden