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Editor—Familial testicular cancer has been extensively studied but its gene(s) locus is yet to be localised. This is probably related to the fact that the majority of these families are small with possibly reduced penetrance and genetic heterogeneity. Recently, an increase in CAG/CTG tract size was reported in five families examined and this germline transmission of expanded (CAG)n tracts was postulated to play a role in testicular tumorigenesis.1 Polycystic kidney disease is a genetically heterogeneous disease with at least three disease loci: one in chromosome 16 (PKD1), one in chromosome 4 (PKD2), and one or more yet to be determined.2
We describe here a family with familial testicular cancer and familial polycystic kidney disease (PKD1). The proband (fig 1, III.5) is a 50 year old white man with polycystic kidney disease and deteriorating kidney function who was referred for possible renal transplantation. In his family, six other family members including his father also have polycystic kidney disease (fig 1). Both he and his late father had also had a testicular cancer removed at the age of 33 and 54, respectively. Both tumours were histologically confirmed to be testicular seminoma. Linkage analysis was performed as previously described1 with nine polymorphic microsatellite markers flanking PKD1 and five flanking PKD2: KG8-(PKD1)-D16S291-W5.2-D16S6633 and D4S3243- D4S2361-D4S1647-AFM353tc1-(PKD2)-D4S1563.2 The PKD1 haplotypes are shown in fig 1. All subjects who have no signs or symptoms of disease are considered to be at various degrees of risk depending on their age, as described previously.4 The only modification is that the two subjects in generation II who are over 70 years of age and appeared normal on repeated radiological screening are labelled as unaffected. The lod scores for all markers were all positive, ranging from 0.50-2.22 at a recombination fraction of 0, supporting linkage to PKD1 on chromosome 16p13.3. The linkage to PKD2 on chromosome 4 was excluded by haplotyping and linkage analysis (data not shown).
In addition, we also sought to verify the previous report of an increase in CAG/CTG tract size in familial testicular cancer. By using the trinucleotide repeat expansion detection method (RED),5 we analysed this family and seven additional white families with isolated familial testicular cancer, one previously reported,6 one unreported, and five from the international consortium on familial testicular cancer. Six of these families have affected sibs and one affected father and son. RED products of ⩾150 nucleotides (nt) were scored as expansions. Only two out of eight probands (25%) were found to have CAG expansions, one with 210 nt and one with 180 nt, and six had 120 nt. This is in agreement with the frequency (29%) previously observed in a normal white population.7
We would like to stress that the association of familial testicular cancer and PKD1 in this family could well be coincidental with two distinct genes coinherited in the family. Still, these findings are interesting and have not been described before. Besides chance coincidence, a common aetiology for both conditions cannot be ruled out, especially in view of the fact that the kidney and testis share the same embryological origin, the urogenital ridge. This might suggest a common genetic trigger involved in a common developmental pathway. Another possibility is that the two causal genes might be located close together forming a contiguous gene syndrome. However, 16p13.3 where PKD1 is located has not been implicated as a candidate region for familial testicular cancer.8 Obviously further molecular and functional studies would be required to dissect out these possibilities.
Finally, we failed to find any evidence of excess CAG/CTG expansions in our series as compared with the general white population. We thus dispute the significance and role of this mechanism in the tumorigenesis of familial testicular cancer.