Suggestive genetic linkage to chromosome 11p11.2-q12.2 in hereditary prostate cancer families with primary kidney cancer.
BACKGROUND
The Seattle-based PROGRESS study was started in 1995 to ascertain hereditary prostate cancer (HPC) families for studies of genetic susceptibility. Subsequent studies by several research groups, including our own, suggest that HPC is a genetically heterogeneous disease. To be successful in mapping loci for such a complex disease, one must consider ways of grouping families into subsets that likely share the same genetic origin. Towards that end, we analyzed a genome-wide scan of HPC families with primary kidney cancer.


METHODS
An 8.1 cM genome-wide scan including 441 microsatellite markers was analyzed by both parametric and non-parametric linkage approaches in fifteen HPC families with the co-occurrence of kidney cancer.


RESULTS
There was no evidence for significant linkage in the initial findings. However, two regions of suggestive linkage were observed at 11q12 and 4q21, with HLOD scores of 2.59 and 2.10, respectively. The primary result on chromosome 11 was strengthened after excluding two families with members who had rare transitional cell carcinoma (TCC). Specifically, we observed a non-parametric Kong and Cox P-value of 0.004 for marker D11S1290 at 11p11.2. The 8 cM region between 11p11.2 and 11q12.2 was refined by the addition of 16 new markers. The subset of HPC families with a median age of diagnosis >65 years demonstrated the strongest evidence for linkage, with an HLOD = 2.50. The P-values associated with non-parametric analysis ranged from 0.004 to 0.05 across five contiguous markers.


CONCLUSIONS
Analysis of HPC families with members diagnosed with primary renal cell carcinoma demonstrates suggestive linkage to chromosome 11p11.2-q12.2.
Johanneson
Bo
B
Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Deutsch
Kerry
K
McIntosh
Laura
L
Friedrichsen-Karyadi
Danielle M
DM
Janer
Marta
M
Kwon
Erika M
EM
Iwasaki
Lori
L
Hood
Leroy
L
Ostrander
Elaine A
EA
Stanford
Janet L
JL
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000556:secondary*
D014408:Biomarkers, Tumor