Prostate cancer (PCa) is the most common malignancy in the urogenital system of men and has a high lethality. In the Asian population, although PCa incidence remains at a relatively low level, it keeps increasing [
Abnormal cell cycle regulation can lead to the occurrence of cancer [
Recently, some publications have reported the association between
Relevant literatures were collected from PubMed, Google Scholar, Web of Science, CNKI, and Wanfang Data databases up to March 2017, using the following retrieval types: (“p27” OR “CDKN1B” OR “V109G” OR “rs2066827”) AND (“polymorphism” OR “mutation” OR “variant” OR “SNP” OR “genotype”) AND (“cancer” OR “carcinoma” OR “tumor”). Articles satisfied with the following inclusion criteria would be enrolled: (1) studies investigated the association between
Statistical analyses were conducted by STATA 12.0 software (StataCorp., College Station, TX). The common measure of association across studies, ORs corresponding with 95% CIs were applied to evaluate cancer susceptibility. Pooled ORs of four genetic models were computed: allelic contrast, heterozygote, homozygote dominant, and recessive models. Chi-square test-based Q test was adopted to measure the heterogeneity across studies. In addition, the Hardy–Weinberg equilibrium (HWE) of control groups was calculated using chi-square test. The stability of results was estimated by sensibility analysis, and publication bias was estimated by Begg’s funnel plot and Egger’s regression test. Statistically significance was set at
In this study, both patients and controls were recruited from the Department of Urology, the First Affiliated Hospital of Anhui Medical University. A total of 90 PCa patients and 140 controls were enrolled for this work between September 2014 and July 2016. Patients were newly diagnosed and pathologically confirmed as PCa, and control groups were almost age-matched, with normal prostate-specific antigen (PSA) levels (<4 ng/ml), without cancer history. Each participant signed an informed consent. We also collected relevant clinicopathologic data, as well as body mass index (BMI), systolic blood pressure (SBP), and serum PSA levels from medical record review.
The genomic DNA of each participant was extracted from blood sample by using commercially DNA extraction kits (Qiagen, catalog: 51106). For each DNA sample,
HWE of controls was calculated by chi-square statistics. The cancer risk, which was assessed by ORs with 95% CI, was calculated by using logistic regression models; otherwise, calculation results were adjusted for age and BMI.
We performed an updated meta-analysis to evaluate the association between
Overall, a significant decreased risk of overall cancer was identified in three genetic models (G versus T: OR = 0.859, 95% CI: 0.764–0.967,
In addition, sensitivity analysis suggested that overall results did not change obviously and remained robust after removing any of the individual research, which proved the stability of our results (Supplementary Table
Furthermore, in order to validate the evidence-based findings obtained above, which suggested that
Table
Characteristics of PCa cases and controls in a Chinese population.
Characteristic | Case | Control | OR (95% CI) | |
---|---|---|---|---|
Sample size | ||||
Age (years ± SD) | 73.00 ± 7.64 | 67.66 ± 6.69 | <0.001 | |
Age (years) | <0.001 | 3.715 (2.128–6.487) | ||
≤70 | 34 | 97 | ||
>70 | 56 | 43 | ||
BMI | 0.098 | 1.661 (0.910–3.030) | ||
≤23 | 21 | 47 | ||
>23 | 69 | 93 | ||
Systolic blood pressure | 0.787 | 1.076 (0.633–1.827) | ||
<140 | 44 | 71 | ||
≥140 | 46 | 69 |
aTwo-sided
The genotypic distributions of
Relationship between the
Genotype | Cases | Controls | OR (95% CI) | OR (95% CI)b | |
---|---|---|---|---|---|
TT | 77 | 127 | 1.00 (reference) | ||
TG | 13 | 13 | 0.231 | 1.649 (0.727–3.742) | 2.132 (0.881–5.155) |
GG | 0 | 0 | — | — | — |
TG/GG | 13 | 13 | 0.231 | 1.649 (0.727–3.742) | 2.132 (0.881–5.155) |
T | 167 | 267 | 0.246 | 1.00 (reference) | |
G | 13 | 13 | 1.599 (0.724–3.532) | — |
aTwo-sided x2 test for the distributions between the cases and controls; badjusting for age and body mass index (BMI).
Stratification analysis of
Group | TT | TG/GG | OR (95% CI) | ||
---|---|---|---|---|---|
Age | |||||
≤70 | 34/97 | 28/85 | 6/12 | 0.444 | 1.518 (0.521–4.421) |
>70 | 56/43 | 49/42 | 7/1 | 0.100 | 6.000 (0.709–50.765) |
BMI | |||||
≤23 | 21/47 | 19/42 | 2/5 | 0.889 | 0.884 (0.157–4.973) |
>23 | 69/93 | 58/85 | 11/8 | 0.157 | 2.015 (0.764–5.315) |
Systolic blood pressure | |||||
<140 | 44/71 | 37/62 | 7/9 | 0.627 | 1.303 (0.448–3.793) |
≥140 | 46/69 | 40/65 | 6/4 | 0.188 | 2.437 (0.648–9.171) |
aTwo-sided
For genotypic comparison, patients with different Gleason grades (based on degree of differentiation between cells, low grade < 7 and high grade > 7), clinical stages [based on international tumor-node-metastasis (TNM) system for PCa, localized and advanced], and PSA levels (PSA ≤ 20 ng/ml and PSA > 20 ng/ml) were subcategorized into 2 subgroups. However, no significant association was also observed in all these subgroups (Table
Group | TT (%) | TG/GG (%) | OR (95% CI) | OR (95% CI)b | |
---|---|---|---|---|---|
Clinicalc | 0.161 | 0.222 (0.027–1.816) | — | ||
Localized | 56 | 12 | |||
Advanced | 21 | 1 | |||
Gleason | 0440 | 1.600 (0.453–5.652) | 1.651 (0.463–5.890) | ||
>7 | 32 | 4 | |||
≤7 | 45 | 9 | |||
Total PSA (ng/ml) | 0.972 | 0.875 (0.269–2.848) | 0.978 (0.290–3.296) | ||
>20 | 33 | 6 | |||
≤20 | 44 | 7 |
aTwo-sided
As we all know, etiology of PCa remains unclear. It has been postulated that many factors can result in malignant neoplasms. In recent decades, many researchers drew attention to the association between genetic polymorphisms and cancer susceptibility [
According to the literatures, several variants located in
Previously, several publications have studied the association between rs2066827 polymorphism and PCa risk in different ethnicities [
Although we have carried out a comprehensive retrieval on diverse databases, and obtained a convincible evidence-based results, which were also validated by a H-B based case-control study, there are still several limitations that should be noted in our study. First, only studies published in English or Chinese were included, which will result in potential study selection bias. Second, for PCa, they are only three case-control studies included and, of them, two generated from an Asian (Chinese) population. Although we obtained a positive association between
Taken together, the current work suggests that
There is no conflict of interest in this article.
All authors agreed to publish this work and contributed to the design, data extraction, data analysis, chart drawing drafting, and revising of the article. All authors are committed to being responsible for their work. Meng Zhang, Qianjun Liang, and Ligang Zhang performed the experiments, literature search, data extraction, and statistical analysis and wrote the manuscript. Zongyao Hao, Jun Zhou, Ligang Zhang, Song Fan, and Chaozhao Liang supervised the literature search, data extraction, and analysis. Meng Zhang, Chaozhao Liang, and Qianjun Liang reviewed the manuscript. Meng Zhang and Qianjun Liang contributed equally to the work.
Supplementary Table 1: main characteristics of all studies included in the meta-analysis. Supplementary Table 2: the overall analyses of