Elevated serum triiodothyronine (t3) in Ashkenazi Jewish prostate cancer patients carrying the I1307k allele of the APC (adenopolyposis coli) gene.
OBJECTIVE
The risk of developing any cancer in carriers of the I1307K mutation of the adenopolyposis coli (APC) gene is significantly increased (odds ratio 1.5, P = 0.01). One of the cancers associated with the I1307K mutation is prostate cancer (odds ratio 2.0, P = 0.14). Also, there is an association of APC mutations with thyroid cancer. In this study, we measured triiodothyronine (t3) levels in Ashkenazi Jewish prostate cancer patients, with and without the I1307K mutation of the APC gene.


METHODS
Participants in our study were found through urology and radiation oncology clinics in 1999 and 2000. All eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. The I1307K allele of the APC gene was detected by amplification of DNA isolated from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Serum t3 level was determined by fluorescent immunoassay with a standard, commercially available instrument.


RESULTS
We studied 77 patients. The youngest patient was 46, the oldest 88, average age 67 +/- 7.2 (mean +/- SD). Eleven males carrying the APCI 1307K allele had significantly higher serum t3 levels than 66 males carrying the wild type allele. There were no homozygotes for the I1307K allele. None of the males had a t3 level that was above the normal range for our laboratory (137 ng/dl).


CONCLUSIONS
Our findings of increased serum t3 level with the APC I1307K allele in prostate cancer patients is not surprising, given the mitogenic potential of t3. Further studies may clarify whether t3 elevation is the mechanism whereby APC gene mutations increase the risk of prostate cancer, or whether other pathophysiologic abnormalities are involved.
Lehrer
Steven
S
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York, USA.
Diamond
Edward J
EJ
Stone
Nelson N
NN
Droller
Michael J
MJ
Stock
Richard G
RG
Stone
Michelle
M
Bajwa
Asghar
A
Kornreich
Ruth
R
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017491:Genes, APC; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics*; D014284:Triiodothyronine / Q000097:blood*
D014284:Triiodothyronine