Case-control study in basal cell carcinoma of the skin: single nucleotide polymorphisms in three interleukin promoters pre-analysed in pooled DNA.
BACKGROUND
Basal cell carcinoma (BCC) is one of the most common neoplasms in the world. Development of BCC is associated with environmental factors (especially sun exposure) as well as heritable factors.


OBJECTIVE
To analyse three single nucleotide polymorphisms (SNPs) in the promoter regions of interleukin (IL) genes in genomic DNA from 527 cases of BCC and 530 matched controls and to examine if DNA pooling is a useful method on which to base decisions regarding further SNP analysis.


METHODS
The SNPs analysed were IL6-597, IL10-1082 and IL1B-511. The SNPs were first analysed from pooled DNA and afterwards from individual samples. The DNA pools resulted from a division of the samples into cases and controls, female and male, and three age groups. In these pools the allele frequencies were estimated by two methods, real-time polymerase chain reaction with allele-specific primers, and quantitative sequencing.


RESULTS
No significant association was found when the allele frequencies in cases and controls were compared. However, by analysis of the individual genotypes we found SNP IL6-597 G/A to be significantly associated with BCC risk (P =0.007). Hereby the heterozygous genotype 'GA' had a protective effect (odds ratio 0.64, 95% confidence interval 0.49-0.84). No significant association was found for IL10-1082 and IL1B-511.


CONCLUSIONS
The association of SNP IL6-597 with BCC could be found only by individual genotyping, but would have been missed if only data from the pooling analysis had been known.
Wilkening
S
S
Department of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany. stefan_wilkening@web.de
Hemminki
K
K
Rudnai
P
P
Gurzau
E
E
Koppova
K
K
Kumar
R
R
Försti
A
A
D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics*
D053583:Interleukin-1beta; D015850:Interleukin-6; D016753:Interleukin-10