Dataset Information

DPP4 genetic variants influence baseline prostate-specific antigen levels: the J-MICC study.

ABSTRACT: Prostate specific antigen (PSA) testing plays a major role in prostate cancer screening; however, the low positive predictive value of PSA testing leads to many unnecessary biopsies. Genetic background is one of factors that could cause it. That's why an association between genetic background and PSA levels should be elucidated. This study aimed to investigate whether DPP4 genetic variants are associated with baseline PSA levels. A cross-sectional study was performed on 2,074 Japanese men aged between 35 and 69 in the Shizuoka area from the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Three DPP4 tagging single nucleotide polymorphisms (SNPs) were selected for genotyping: rs3788979 (A/G), rs7608798 (T/C), and rs2268889 (A/G). Higher mean serum PSA levels were significantly associated with an increase in the number of the rs7608798 C allele (p for trend = 0.02). A stratified analysis by age groups demonstrated that PSA levels had positive significant trends with the numbers of the minor alleles of rs3788979 or rs7608798 in the oldest group (men aged between 60 and 69) (p for trend=0.004 for rs3788979 and p for trend=0.001 for rs7608798). Haplotype analysis showed that the C-A (rs7608798-rs2268889) haplotype was significantly associated with increased PSA levels (p=0.006), compared with the most common haplotype, T-A. In summary, our study suggests that DPP4 genetic variants influence baseline PSA levels, especially in men aged between 60 and 69.

SUBMITTER: Higashibata T

PROVIDER: S-EPMC4345699 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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DPP4 genetic variants influence baseline prostate-specific antigen levels: the J-MICC study.

Higashibata Takahiro T Naito Mariko M Mori Atsuyoshi A Ozawa Noriyo N Furuta Masatoshi M Tsuchiya Rumi R Koyama Erina E Morita Emi E Kawai Sayo S Okada Rieko R Yin Guang G Wakai Kenji K Hamajima Nobuyuki N

Nagoya journal of medical science 20130201 1-2

Prostate specific antigen (PSA) testing plays a major role in prostate cancer screening; however, the low positive predictive value of PSA testing leads to many unnecessary biopsies. Genetic background is one of factors that could cause it. That's why an association between genetic background and PSA levels should be elucidated. This study aimed to investigate whether DPP4 genetic variants are associated with baseline PSA levels. A cross-sectional study was performed on 2,074 Japanese men aged b ...[more]

PMID: 23544270

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Project description:ObjectiveTo validate six previously identified markers among men at increased risk of prostate cancer (African-American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.Patients and methodsEligibility criteria for PRAP include age 35-69 years with a family history of prostate cancer, African-American ethnicity regardless of family history, and known BRCA gene mutations. The genome-wide association study markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12) and rs17632542 (19q13.33). Genotyping methods included either the Taqman(®) single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders.ResultsA total of 707 participants (37% Caucasian, 63% African-American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) was strongly associated with PSA levels among Caucasian participants in the high-risk group (P < 0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) was found to be associated with PSA level (P = 0.03) in Caucasian men in the high-risk group, with a 15% increase in PSA level with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 was proposed, specific to high-risk Caucasian men.ConclusionsGenetic variation at 10q may be particularly important in personalizing the interpretation of PSA level for Caucasian men in the high-risk group. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for Caucasian men in the high-risk group, although further study is warranted.

Project description:BACKGROUND:Prostate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men. OBJECTIVE:To determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men. DESIGN, SETTING, AND PARTICIPANTS:Nested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A prospective cohort in the southeastern USA with recruitment from community health centers. A total of 197 incident PCa patients aged 40-64 yr at study entry and 569 controls matched on age, date of blood draw, and site of enrollment. Total PSA was measured in blood collected and stored at enrollment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Total and aggressive PCa (91 aggressive: Gleason ?7, American Joint Committee on Cancer stage III/IV, or PCa-specific death). Exact conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) for PCa by category of baseline PSA. RESULTS AND LIMITATIONS:Median PSA among controls was 0.72, 0.80, 0.94, and 1.03ng/ml for age groups 40-49, 50-54, 55-59, and 60-64 yr, respectively; 90th percentile levels were 1.68, 1.85, 2.73, and 3.33ng/ml. Furthermore, 95% of total and 97% of aggressive cases had baseline PSA above the age-specific median. Median follow-up was 9 yr. The OR for total PCa comparing PSA >90th percentile versus ?median was 83.6 (95% CI, 21.2-539) for 40-54 yr and 71.7 (95% CI, 23.3-288) for 55-64 yr. For aggressive cancer, ORs were 174 (95% CI, 32.3-infinity) for 40-54 yr and 51.8 (95% CI, 11.0-519) for 55-64 yr. A composite endpoint of aggressive PCa based on stage, grade, and mortality was used and is a limitation. CONCLUSIONS:PSA levels in midlife strongly predicted total and aggressive PCa among black men. PSA levels among controls were similar to those among white controls in prior studies. PATIENT SUMMARY:Prostate-specific antigen (PSA) level during midlife strongly predicted future development of aggressive prostate cancer among black men. Targeted screening based on a midlife PSA might identify men at high risk while minimizing screening in those men at low risk.

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Dataset Information

DPP4 genetic variants influence baseline prostate-specific antigen levels: the J-MICC study.

Publications

DPP4 genetic variants influence baseline prostate-specific antigen levels: the J-MICC study.

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