8q24 and 17q prostate cancer susceptibility loci in a multiethnic Asian cohort.
OBJECTIVES
Recently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men.


MATERIALS AND METHODS
We performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP.


RESULTS
In the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04-2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥ 7 (OR = 1.76, 95% CI = 1.14-2.73) and prostate-specific antigen (PSA) levels of ≥ 10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01-2.63), as well as for rs6983267 GG with stage 3-4 CaPs (OR = 1.91, 95% CI = 1.01-3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10-4.32).


CONCLUSIONS
This exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.
['Chan|Jason Yongsheng|JY|', 'Li|Huihua|H|', 'Singh|Onkar|O|', 'Mahajan|Anupama|A|', 'Ramasamy|Saminathan|S|', 'Subramaniyan|Koilan|K|', 'Kanesvaran|Ravindran|R|', 'Sim|Hong Gee|HG|', 'Chong|Tsung Wen|TW|', 'Teo|Yik-Ying|YY|', 'Chia|Sin Eng|SE|', 'Tan|Min-Han|MH|', 'Chowbay|Balram|B|']
D000368:Aged D000483:Alleles D044466:Asians D016022:Case-Control Studies D002681:China D002886:Chromosomes, Human, Pair 17 D002898:Chromosomes, Human, Pair 8 D005787:Gene Frequency D056426:Genetic Loci D020022:Genetic Predisposition to Disease D005838:Genotype D006801:Humans D007194:India D016015:Logistic Models D008296:Malaysia D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D016017:Odds Ratio D020641:Polymorphism, Single Nucleotide D017430:Prostate-Specific Antigen D011471:Prostatic Neoplasms D012846:Singapore
Prostate Cancer Polymorphism Gleason Ethnicity Pharmacogenetics