Importance Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. Objective To estimate familial risk and heritability of cancer types in a large twin cohort. Design, Setting, and Participants Prospective study of 80 309 monozygotic and 123 382 same-sex dizygotic twin individuals (N = 203 691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50 990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. Exposures Shared environmental and heritable risk factors among pairs of twins. Main Outcomes and Measures The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. Results A total of 27 156 incident cancers were diagnosed in 23 980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). Conclusions and Relevance In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.
Background Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that presence of PNI in prostate cancer has been associated with cancer aggressiveness. Methods We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death. Results The prevalence of PNI was 7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer (odds ratio, OR, 7.4, 95% confidence interval, CI, 3.6, 16.6; p<0.001). A positive, though not statistically significant, association persisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9, 95% CI 0.8, 5.1; p=0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8, 95% CI 1.0, 3.3; p=0.04). Conclusion These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness. Impact Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis.
Background ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. Methods We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype and risk of aggressive prostate cancer (Gleason score ≥8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). Results We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR=0.97, 95% CI=0.87-1.08; Type B: OR=0.92, 95% CI=0.77-1.09; Type AB: OR=1.25, 95% CI=0.98-1.59, compared to Type O, respectively). Similarly, there was no association between ‘dose’ of A or B alleles and aggressive prostate cancer risk. Conclusions ABO blood type was not associated with risk of aggressive prostate cancer.
Background: Corpora amylacea are amyloid bodies commonly found adjacent to damaged prostate epithelium. Little is known about their formation or function. The current study sought to characterize corpora amylacea in prostate tissue and to describe their relationship with clinical, histological, molecular and lifestyle factors, especially with chronic inflammation which is associated with aggressive disease. Methods: We studied a cohort of 355 men with prostate cancer and tissue specimens from the Health Professionals Follow-up Study. Pathologists examined H&E slides and undertook a standardized review for histologic data and inflammation. Trained observers counted corpora amylacea within the benign and predominately tumor areas. Immunohistochemistry biomarkers were available from tissue microarrays. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) to assess associations of chronic inflammation, clinical, histological, molecular and lifestyle factors with the presence of corpora amylacea. Results: Corpora amylacea were present in benign tissue area for 298 men (84%). Specimens with moderate to severe chronic inflammation were more likely to have corpora amylacea in benign regions (OR=5.4 95% CI 1.9, 15.6). Moreover, corpora amylacea were more common in men with higher body mass index (OR=1.13 95% CI 1.01, 1.26). In contrast, Gleason grade (OR=0.4 95% CI 0.2, 0.8), proliferation index (OR=0.6 95% CI 0.3, 1.2) and presence of the TMPRSS2:ERG fusion (OR=0.4 95% CI 0.2, 0.8) were inversely associated with corpora amylacea presence. TURP specimens were less likely to have corpora amylacea than prostatectomy specimens (OR=0.12 95% CI 0.03, 0.47). Age, PSA, stage, biomarkers of angiogenesis and PTEN, and vasectomy were not significantly associated with corpora amylacea. Conclusion: Corpora amylacea were common among men with prostate cancer and were associated with pro-inflammatory factors, some markers of less aggressive disease, and lack of the TMPRSS2:ERG fusion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.