Conceived and designed the experiments: CT WK DS. Performed the experiments: DS HJ KK EK YB. Analyzed the data: CT WK. Contributed reagents/materials/analysis tools: WK TY SK. Wrote the paper: CT WK.
The authors have declared that no competing interests exist.
The Y chromosome has recently been suggested to have an association with prostate cancer risk in human populations. Since this chromosome is haploid and lacks recombination over most of its length, haplotypes constructed from binary markers throughout the chromosome can be used for association studies. To assess the possible Y-chromosomal contribution to prostate cancer risk, we have therefore analyzed 14 Y-chromosomal binary markers in 106 prostate cancer cases and 110 controls from the Korean population. In contrast to previous findings in the Japanese population, no statistically significant difference in the distribution of Y-chromosomal haplogroup frequencies was observed between the case and control groups of Koreans. Thus, our data imply that the previously reported associations between Y-chromosomal lineages and a predisposition to, or protection against, prostate cancer might be explained by statistical fluctuations, or by genetic effects that are seen only in some environments.
Prostate cancer is one of the most common male-specific cancers, but its incidence varies considerably between populations, with the chance of developing this cancer being highest in Western countries and lowest in Asian countries. Recent surveys suggest that both genetic alterations and dietary factors may be linked to prostate cancer
There is increasing evidence for a Y-chromosomal role in malignancy and male-specific cancer progression. Y-chromosomal mutations are associated with prostate cancer, since the loss of this chromosome is the most common chromosomal aberration observed in prostate cancer tissue
The Y chromosome has special genetic features that include an absence of recombination over most of its length and haploid status. The DNA sequence of the non-recombining region of the Y chromosome therefore contains a record only of the mutational events that occurred in the past. As a consequence, haplotypes constructed from Y-chromosomal alleles have been successfully used to study paternal lineages
Interestingly, recent studies have suggested that certain Y-chromosomal lineages were associated with prostate cancer risk in the Japanese population
In the present study, we have therefore investigated the association between Y-chromosomal haplogroups and a predisposition to prostate cancer in the Korean population by examining 106 prostate cancer cases and 110 controls using 14 Y-chromosomal binary markers.
We observed eleven different Y-chromosomal lineages defined by the fourteen binary markers in the cancer cases and control samples, most of which are the expected predominant haplogroups in east Asia. Frequency distributions of the fourteen binary markers and corresponding Y-chromosomal haplogroups are listed in
Y-chromosomal haplogroup distribution in prostate cancer cases and controls in the Korean population. The parsimonious tree on the top shows the evolutionary relationship of fifteen haplogroups. Nomenclature is according to the Y Chromosome Consortium
Paracchini et al. |
This study | |||
O-M122 | Y*(xO-M122) | O-M122 | Y*(xO-M122) | |
Prostate cancer | 56 (25%) | 167 (75%) | 52 (49%) | 54 (51%) |
Normal controls | 56 (17%) | 272 (83%) | 50 (45%) | 60 (55%) |
OR (95% CI) | 1.63 (1.07–2.47) | 1.16 (0.68–1.97) | ||
p value | 0.02 | 0.60 | ||
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Prostate cancer | 20 (22%) | 72 (78%) | 29 (27%) | 77 (73%) |
Normal controls | 41 (38%) | 68 (62%) | 29 (26%) | 81 (74%) |
OR (95% CI) | 0.46 (0.25–0.86) | 1.05 (0.58–1.92) | ||
p value | 0.01 | 0.87 |
Abbreviations: CI, confidence interval; OR, odds ratio
No statistically significant difference (p<0.05) in the distribution of Y-chromosomal haplogroup frequencies was observed between the case and control groups (
Distribution of the haplogroup O-M122-derived lineages versus all other lineages combined in Korean prostate cancer patients surveyed here
Ages/Disease status | Haplogroup O-M122-derived | Other | Total |
All | 52 | 54 | 106 |
<65 | 15 | 12 | |
≥65 | 37 | 42 | 106 |
low severity† | 19 | 19 | |
high severity† | 31 | 34 | 103 |
Stratifying by age: OR 1.50 (0.64–3.50), p = 0.35; stratifying by disease severity: OR 1.09 (0.59–2.02), p = 0.77. †Low severity: local stage and Gleason grade <8; high severity: local stage+Gleason grade 8 and/or regional/metastatic stage. Numbers do not sum to all cases due to missing data for patients' Gleason grade.
Recent surveys from Asia (e.g., Japan, Singapore and Korea) have shown a general trend of a rising incidence of prostate cancer, although the incidence is still lower in Asia than in Western countries
We analyzed a total of 106 Korean prostate cancer patients, who were recruited for the study from the urology department of the Eulji University School of Medicine in Seoul and Daejeon, Korea. Histological classification of prostate cancer was determined according to the World Health Organization (WHO) recommendation and the Gleason pattern. Prostate cancer tissue specimens from all of the patients were collected from frozen samples. In addition, a total of 110 Korean men who had been diagnosed as free of prostate cancer by the Eulji University hospital in Seoul and Daejeon, Korea were recruited as normal controls. These subjects were selected at random (and therefore likely to be unrelated) from the same geographical area as the cases. This study was approved by the Ethics Committee of Eulji Medical Center of the Eulji University School of Medicine in Seoul, and informed consent was obtained from all participants.
DNAs were prepared from the prostate cancer specimens of patients and whole blood samples of controls according to standard methods
Fourteen Y-chromosomal binary markers were chosen to genotype all individuals sampled: YAP
The M7 (C to G substitution), M134 (−1 bp), M214 (T to C substitution), M119 (A to C substitution), P31 (T to C substitution), and M122 (T to C substitution) markers were amplified using the following primer sets and modifications reported by Hammer et al.
Y-chromosomal binary haplogroups for all samples of prostate cancer cases and controls were defined by the analysis of all 14 binary polymorphisms. The nomenclature of the haplogroups followed that of the Y chromosome consortium (YCC)
Y haplogroup frequencies were calculated by counting from the observed phenotypes. To test for significant population differentiation between the prostate cancer cases and the control groups, we used a Chi squared test and Fisher exact test implemented in the Arlequin package version 2.0
We would like to thank all volunteers for providing DNA samples for making this study possible. Special thanks go to all the urologists and pathologists in Eulji Medical Center of the Eulji University hospital.