Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.
OBJECTIVE
To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues.


METHODS
The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks.


RESULTS
The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity.


CONCLUSIONS
NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence CaP evolution. The CaP specimens from the NJ and J-A men were histologically similar, but tissue biomarker expression, especially of lipoxygenase and the caspase family, suggested differing mechanisms of carcinogenesis. Differences in nuclear morphometry suggested the additional possibility of gene-nutrient interactions.
Marks
Leonard S
LS
Department of Urology, University of California, Los Angeles, Geffen School of Medicine, Los Angeles, California, USA.
Kojima
Munekado
M
Demarzo
Angelo
A
Heber
David
D
Bostwick
David G
DG
Qian
Junqi
J
Dorey
Frederick J
FJ
Veltri
Robert W
RW
Mohler
James L
JL
Partin
Alan W
AW
D000230:Adenocarcinoma / Q000097:blood / Q000737:chemistry / Q000208:ethnology* / Q000209:etiology / Q000652:urine; D000368:Aged; D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis; D001213:Asian; D044466:Asian People; D015415:Biomarkers; D014408:Biomarkers, Tumor; D001823:Body Composition; D002467:Cell Nucleus / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000648:ultrastructure; D004032:Diet; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000009:adverse effects; D004958:Estradiol / Q000097:blood; D005247:Feeding Behavior; D019833:Genistein / Q000652:urine; D006801:Humans; D007529:Isoflavones / Q000652:urine; D007564:Japan / Q000453:epidemiology / Q000208:ethnology; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000097:blood / Q000737:chemistry / Q000208:ethnology* / Q000209:etiology / Q000652:urine; D012189:Retrospective Studies; D045730:Soy Foods; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D014408:Biomarkers, Tumor; D002843:Chromatin; D004041:Dietary Fats; D007529:Isoflavones; D009363:Neoplasm Proteins; D014280:Triglycerides; D004958:Estradiol; C004742:daidzein; D019833:Genistein; D001094:Arachidonate 5-Lipoxygenase