Cancer risks associated with the HOXB13 c.251G> A variant in men and women referred for hereditary cancer genetic testing.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13653-e13653
Author(s):  
Melanie Jones ◽  
Eric Thomas Rosenthal ◽  
Karen Copeland ◽  
John Kidd ◽  
Ryan Bernhisel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Hereditary Cancer ◽  
Prostate Cancer Risk ◽  
Cancer Risks ◽  
Increased Risk ◽  
Males And Females ◽  
Male Carriers ◽  
Female Carriers

e13653 Background: The HOXB13 c.251G > A (p.G84E) variant is associated with increased prostate cancer risk, possibly at younger ages. Studies on this variant have focused primarily on men, although genetic testing for hereditary cancer risk is most often performed in women. There remains a need to assess whether male and female carriers of this variant have increased risk for other cancers. Methods: We identified male and female carriers of the HOXB13 c.251G > A (p.G84E) variant among individuals referred for hereditary cancer panel genetic testing from October 2018 – December 2019. Non-carriers had no pathogenic variants in any gene or variants of uncertain significance in HOXB13. Personal and family (1st- and 2nd-degree relative) cancer histories were obtained from provider-completed test request forms. Multivariable logistic regression (MLR) models were conducted separately for males and females to estimate cancer risks for the variant as odds ratios (ORs), and 95% Wald confidence intervals (CIs) adjusted for age, ancestry and personal/family cancer history. Results: The analysis included 197,978 patients: 4.5% (8,998/197,978) male and 95.5% (188,980/197,978) female. The HOXB13 variant was present in 0.44% (40/8,998) of tested males, 45% (18/40) of whom had a diagnosis of prostate cancer. The variant was present in 0.32% (621/188,980) of tested females. Male carriers with prostate cancer were diagnosed at younger ages (median, 56; Interquartile ratio [IQR], 52, 62) than non-carriers (median, 63; IQR, 57,70), but this difference was not statistically significant. The MLR model calculated a 3.30 OR for prostate cancer in male carriers of c.251C > A ( P = 0.01; 95% CI 1.30-8.39). In an analysis combining males and females, carriers were significantly more likely to report prostate cancer in a family member than non-carriers ( P = 3.5 x 10−7; OR 1.61, 95% CI 1.34-1.93). There was no apparent association with increased risk for other cancers among carriers versus non-carriers, or among relatives of carriers compared with relatives of non-carriers. Conclusions: The HOXB13 c.251G > A (p.G84E) variant was associated with significantly increased risk of prostate cancer, confirming previously published studies. We found no evidence of association with other cancers. For unaffected male carriers, who may frequently be identified through testing of a female relative, identification of this HOXB13 variant provides an opportunity for more precise prostate cancer risk stratification and screening.

scholarly journals Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

2017 ◽  
Vol 35 (20) ◽  
pp. 2240-2250 ◽  
Author(s):  
Julie Lecarpentier ◽  
Valentina Silvestri ◽  
Karoline B. Kuchenbaecker ◽  
Daniel Barrowdale ◽  
Joe Dennis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Prostate Cancer Risk ◽  
Risk Scores ◽  
Cancer Risks ◽  
Prostate Cancer Susceptibility ◽  
Common Genetic Variants ◽  
Breast And Prostate Cancer ◽  
Male Carriers

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10−6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10−9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

scholarly journals Social Jetlag and Prostate Cancer Incidence in Alberta’s Tomorrow Project: A Prospective Cohort Study

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3873
Author(s):  
Liang Hu ◽  
Andrew Harper ◽  
Emily Heer ◽  
Jessica McNeil ◽  
Chao Cao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Repeated Measures ◽  
Prospective Cohort ◽  
Prostate Cancer Risk ◽  
Absolute Difference ◽  
Prostate Cancer Incidence ◽  
Social Jetlag ◽  
Increased Risk

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35–69 years enrolled in Alberta’s Tomorrow Project (ATP) from 2001–2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0–<1 h (from 0 to anything smaller than 1), 1–<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (n = 250). Hazard ratios (HR) were estimated using Cox proportional hazards regressions, adjusting for a range of covariates. Median follow-up was 9.57 years, yielding 68,499 person-years. Baseline presence of social jetlag of 1–<2 h (HR = 1.52, 95% CI: 1.10 to 2.01), and 2+ hours (HR = 1.69, 95% CI: 1.15 to 2.46) were associated with increased prostate cancer risk vs. those reporting no social jetlag (p for trend = 0.004). These associations remained after adjusting for sleep duration (p for trend = 0.006). With respect to chronotype, the association between social jetlag and prostate cancer risk remained significant in men with early chronotypes (p for trend = 0.003) but attenuated to null in men with intermediate (p for trend = 0.150) or late chronotype (p for trend = 0.381). Our findings suggest that greater than one hour of habitual social jetlag is associated with an increased risk of prostate cancer. Longitudinal studies with repeated measures of social jetlag and large samples with sufficient advanced prostate cancer cases are needed to confirm these findings.

scholarly journals O8A.4 Asbestos exposure and prostate cancer, really?

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A71.1-A71
Author(s):  
Marie-Elise Parent ◽  
M Hugues Richard
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Asbestos Exposure ◽  
Large Population ◽  
Prostate Cancer Risk ◽  
Cumulative Exposure ◽  
Population Exposure ◽  
Specific Information ◽  
Chrysotile Asbestos ◽  
Increased Risk

BackgroundGeneral population exposure to asbestos from residential insulation and from environmental sources during childhood have recently been associated with prostate cancer. While asbestos fibers can be found in the prostate of workplace-exposed men at autopsy, few occupational studies have reported on asbestos exposure and prostate cancer incidence. We examined the association between lifetime occupational exposure to chrysotile asbestos and prostate cancer risk in a large population-based case-control study.MethodsCases were 1933 men with histologically-confirmed incident prostate cancer, aged ≤75 years, diagnosed in 2005–2009 in Montreal. Concurrently, 1994 population controls from the same residential area and age distribution were randomly selected from electoral lists. In-person interviews elicited detailed socio-demographics, lifestyle and work histories. Industrial hygienists used job-specific information to provide semi-quantitative evaluations of intensity and frequency of exposure to 345 chemical agents, including asbestos, and a measure of confidence in the evaluation. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer risk associated with exposure to chrysotile asbestos.ResultsAfter restriction to probable and definite exposure, and application of a 5 year lag, 12.5% of cases and 11.8% of controls were ever exposed to asbestos (OR=1.1, 95% CI 0.9–1.3). For duration of exposure, there was no increase in risk of overall prostate cancer in the lower tertiles of exposure but risk was elevated in the upper tertile (OR=1.6, 95% CI 1.2–2.2). Similarly, for cumulative exposure, risk was elevated in the upper tertile only (OR=1.5, 95% CI 1.1–2.1). Analyses considering tumor grades also showed a higher risk in the upper tertile of cumulative exposure for non-aggressive (OR=1.5, 95% CI 1.1–2.2) and especially aggressive (OR=1.9, 95% CI 1.2–3.0) cancers.ConclusionOur findings are consistent with an increased risk of prostate cancer with prolonged and high cumulative exposure to chrysotile asbestos, and particularly for the aggressive form of the disease.

Aspirin Use is Associated with Lower Prostate Cancer Risk in Male Carriers of BRCA Mutations

2013 ◽  
Vol 23 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Matthew Cossack ◽  
Cameron Ghaffary ◽  
Patrice Watson ◽  
Carrie Snyder ◽  
Henry Lynch
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Brca Mutations ◽  
Male Carriers

scholarly journals How men view genetic testing for prostate cancer risk: findings from focus groups

2000 ◽  
Vol 58 (3) ◽  
pp. 169-176 ◽  
Author(s):  
DJ Doukas ◽  
MD Fetters ◽  
JC Coyne ◽  
LB McCullough
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Focus Groups ◽  
Prostate Cancer Risk

scholarly journals Meta-Analysis of the Relationship between XRCC1-Arg399Gln and Arg280His Polymorphisms and the Risk of Prostate Cancer

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jie Yan ◽  
Xiantao Wang ◽  
Hui Tao ◽  
Zengfu Deng ◽  
Wang Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Prostate Cancer Risk ◽  
Recessive Model ◽  
Dominant Model ◽  
Xrcc1 Arg399gln ◽  
Increased Risk ◽  
Arg399gln Polymorphism ◽  
The Relationship

Abstract Prostate cancer is one of the most common noncutaneous malignancies in Western countries. Because there has been a debate regarding the relationship between the XRCC1-Arg399Gln and Arg280His polymorphisms and prostate cancer risk, we therefore performed this meta-analysis. The electronic databases PubMed, EMBASE and Medline were searched prior to October 1, 2014. An odds ratio and 95% confidence interval were used to calculate association. Heterogeneity was tested by both a chi-square test and I2statistic. Funnel plots and Egger’s test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software. A significant association between the XRCC1-Arg399Gln polymorphism and prostate cancer risk was found under a homozygote model and a recessive model. A significant association between XRCC1-Arg280His and prostate cancer risk was found under a heterozygote model and a dominant model. Overall, the results of this meta-analysis show that the XRCC1-Arg399Gln polymorphism may be associated with an increased risk for prostate cancer under the homozygote model and the recessive model. And XRCC1-Arg280His polymorphism is likely to be related with prostate cancer risk under the heterozygote model and the dominant model. Additional larger well-designed studies are needed to validate our results.

scholarly journals Mendelian randomization does not support serum calcium in prostate cancer risk

2018 ◽  
Author(s):  
James Yarmolinsky ◽  
Katie Berryman ◽  
Ryan Langdon ◽  
Carolina Bonilla ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Causal Inference ◽  
Serum Calcium ◽  
Observational Studies ◽  
Advanced Prostate Cancer ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
A Genome ◽  
Increased Risk

AbstractBackground: Observational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies.Objective: We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer.Design: A genetic instrument was constructed using 5 single nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (N ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls).Results: We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/dL increase in calcium: 0.83, 95% CI: 0.63-1.08; P=0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5 mg/dL increase in calcium: 0.98, 95% CI: 0.57-1.70; P=0.93).Conclusions: Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

scholarly journals Genetic polymorphisms in CDH1 and Exo1 genes elevate the prostate cancer risk in Bangladeshi population

Tumor Biology ◽  
2019 ◽  
Vol 41 (3) ◽  
pp. 101042831983083 ◽  
Author(s):  
Hasnain Imtiaz ◽  
Sharmin Afroz ◽  
Md Amir Hossain ◽  
Sm Faysal Bellah ◽  
Md Mostafizur Rahman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Confidence Interval ◽  
Genetic Polymorphisms ◽  
Odds Ratio ◽  
Prostate Cancer Risk ◽  
Polymorphism Analysis ◽  
Increased Risk ◽  
Bangladeshi Population ◽  
Increased Susceptibility

The polymorphisms of invasion suppressor gene CDH1 and DNA mismatch repair gene Exo1 have been reported to play critical role in the development, tumorigenesis, and progression of several kinds of cancers including prostate cancer. This study was designed to analyze the contribution of single-nucleotide polymorphisms of the CDH1 (-160C/A) and Exo1 (K589E) to prostate cancer susceptibility in Bangladeshi population. The study included 100 prostate cancer cases and age-matched 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genetic polymorphisms. A significant association was found between CDH1 -160C/A (rs16260) and Exo1 (rs1047840, K589E) polymorphisms and prostate cancer risk. In case of CDH1 -160C/A polymorphism, the frequencies of the three genotypes C/C,C/A, and A/A were 45%, 48%, and 7% in cases and 63%, 32%, and 5% in controls, respectively. The heterozygote C/A genotype and combined C/A + A/A genotypes showed 2.10-fold (odds ratio = 2.1000, 95% confidence interval = 1.2956–4.0905, p = 0.013) and 2.08-fold (odds ratio = 2.0811, 95% confidence interval = 1.1820–3.6641, p = 0.011) increased risk of prostate cancer, respectively, when compared with homozygous C/C genotypes. The variant A allele also was associated with increased risk of prostate cancer (odds ratio = 1.6901, 95% confidence interval = 1.0740–2.6597, p = 0.0233). In case of Exo1 (K589E) polymorphism, G/A heterozygote, A/A homozygote, and combined G/A + A/A genotypes were found to be associated with 2.30-, 4.85-, and 3.04-fold higher risk of prostate cancer, respectively (odds ratio = 2.3021, 95% confidence interval = 2.956–4.0905, p = 0.0031; odds ratio = 4.8462, 95% confidence interval = 1.0198–23.0284, p = 0.0291; OR = 3.0362, 95% confidence interval = 1.7054–5.4053, p = 0.0001, respectively). The “A” allele showed significant association with increased susceptibility (2.29-fold) to prostate cancer (odds ratio = 2.2955, 95% confidence interval = 1.4529–3.6270, p = 0.0004). Our results suggest that CDH1 -160C/A and Exo1 K589E polymorphisms are associated with increased susceptibility to prostate cancer in Bangladeshi population.

Germline heterozygous BLM mutations and prostate cancer risk.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 321-321
Author(s):  
Elisa Ledet ◽  
Emmanuel S. Antonarakis ◽  
Colin Pritchard ◽  
William B. Isaacs ◽  
A. Oliver Sartor
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Dna Sequencing ◽  
Cancer Patients ◽  
Genetic Disorder ◽  
Prostate Cancer Risk ◽  
Dna Helicase ◽  
Cancer Center ◽  
Increased Risk

321 Background: The BLM gene encodes a RecQ DNA helicase that is involved in homologous recombination. Biallelic BLM inactivation leads to Bloom syndrome, an inherited genetic disorder marked by chromosomal instability and multiple cancer susceptibilities. Conflicting studies have suggested that heterozygous BLM mutation carriers may have an increased risk of various cancers. Here we explored the role of germline pathogenic BLM mutations in prostate cancer. Methods: Prostate cancer patients with heterozygous BLM mutations were assembled from Tulane Cancer Center (TCC), Johns Hopkins Hospital (JHH) and University of Washington (UW). BLM germline mutations were identified either through commercial germline testing (Invitae), the UW-BROCA panel, or whole-exome sequencing. Corresponding tumor tissue was analyzed by DNA sequencing for somatic alterations. Population level control data were obtained from the Genome Aggregation Database (gnomAD). Results: 6 BLM germline carriers were identified among 985 advanced prostate cancer case; 2/295 TCC patients, 2/172 JHH patients, and 2/518 UW patients. Overall, pathogenic BLM mutations were detected in 0.609% (6/985) of prostate cancer cases. All mutations were loss-of-function truncating lesions (splicing or nonsense alterations). No Ashkenazi BLM mutations were observed. The population frequency of pathogenic or likely pathogenic BLM alterations detected in gnomAD was 0.025% (31/124,589). Compared to gnomAD controls, the relative risk of BLM mutations in prostate cancer patients was 24.3 (95% CI 10.2 to 58.2; P < 0.0001). One family had a pathogenic splice variant in BLM that cosegregated with disease in three of three cases with lethal/high risk prostate cancer. Tumor DNA sequencing was possible in 5 of 6 BLM carriers; no case demonstrated LOH or additional somatic BLM mutations. Interestingly, 2/5 cases on tumor sequencing also had bi-allelic BRCA2 inactivation. Conclusions: Germline BLM mutations may play a role in prostate cancer risk. Given the role of BLM in chromosomal stability and evidence of concurrent BRCA2 inactivation in a subset of cases, larger cohorts and functional analyses will be critical for better understanding the role of BLM in prostate cancer.

scholarly journals Neither Hormonal Factors Nor AGEs Explain Lower Prostate Cancer Risk in Older Men With Diabetes Mellitus

2019 ◽  
Vol 104 (12) ◽  
pp. 6017-6024
Author(s):  
Yi X Chan ◽  
Helman Alfonso ◽  
P Gerry Fegan ◽  
Leon Flicker ◽  
Bu B Yeap
Keyword(s):  
Prostate Cancer ◽  
Diabetes Mellitus ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Sex Hormone ◽  
Inverse Association ◽  
Metabolic Disturbances ◽  
Hormonal Factors ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract Context Diabetes mellitus is conventionally associated with an increased risk of cancer; however, inverse associations of diabetes with prostate cancer are well described. Mechanisms are unclear, although hormonal factors, including alterations in sex hormone and IGF1 concentrations due to metabolic disturbances, have been hypothesized to play a role. Objective To assess sex hormones, IGF1, glucose, and advanced glycation end products (AGEs) as potential mediators of the association between diabetes mellitus and prostate cancer. Design and Participants Longitudinal cohort study. The association of baseline diabetes with prostate cancer incidence was assessed using proportional hazards competing risks analysis in 3149 men followed for 12 years. Baseline hormone, glucose, and carboxymethyllysine (CML) levels were examined as potential mediators of this association. Results Diabetes was associated with a lower prostate cancer risk (fully adjusted subhazard ratio, 0.63; 95% CI, 0.43 to 0.92; P = 0.017). This association was unchanged after accounting for testosterone, DHT, estradiol, or SHBG. Similarly, the addition of IGF1 or its binding proteins 1 and 3, or glucose, did not alter this association. CML was not associated with the risk of prostate cancer, and additional correction for CML in the fully adjusted model did not alter the inverse association of diabetes and prostate cancer risk. Conclusions In this study, alterations in sex hormone, IGF1, glucose, and CML levels did not account for the inverse association of diabetes and prostate cancer risk. Further studies are required to provide more insight into underlying causes of this association.

Sign in / Sign up

Export Citation Format

Share Document