| 1. |
- Jiang, X., et al.
(författare)
-
Shared heritability and functional enrichment across six solid cancers
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Gusev, A, et al.
(författare)
-
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
-
Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Chang, E T, et al.
(författare)
-
Alcohol drinking and risk of localized versus advanced and sporadic versus familial prostate cancer in Sweden
- 2005
-
Ingår i: Cancer Causes and Control. - Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Umea Univ, Dept Radiat Sci Oncol, Umea, Sweden. : SPRINGER. - 0957-5243 .- 1573-7225. ; 16:3, s. 275-284
-
Tidskriftsartikel (refereegranskat)abstract
- Background: It is unknown whether the association of alcohol consumption with prostate cancer risk varies between localized and advanced cases, or between sporadic and familial cases. Methods: We assessed recent alcohol drinking in a population-based case-control study of Swedish men, including 1499 cases and 1130 controls. Drinking status and average volume, frequency, and type of alcohol consumed were evaluated. Unconditional logistic regression was performed to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for associations between alcohol consumption and prostate cancer risk. Results: Prostate cancer cases were more likely than controls to be current or former, rather than never, drinkers. However, there was no association between recent total alcohol, beer, wine, and liquor consumption and risk of overall prostate cancer, nor advanced, sporadic, or familial prostate cancer. The OR for risk of overall disease among men who drank more than 135 g of total alcohol per week versus non-drinkers was 1.2 (95% CI: 0.9, 1.5), p(trend)=0.12. There was a marginal positive association between alcohol intake and risk of localized disease. Conclusions: We detected no association between recent alcohol consumption and risk of advanced, sporadic, or familial prostate cancer, and a borderline positive association with localized disease.
|
|
| 9. |
- Lindmark, F, et al.
(författare)
-
H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer
- 2004
-
Ingår i: Journal of the National Cancer Institute. - Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Umea Univ Hosp, Dept Urol & Androl, S-90185 Umea, Sweden. Wake Forest Univ, Sch Med, Ctr Human Genomics, Winston Salem, NC 27109 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 96:16, s. 1248-1254
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor beta superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer. Methods: The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A statistically significant difference (P = .006) in genotype frequency was observed for the nonsynonymous change H6D) (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95% CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95% CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2% for sporadic cancer and 19.2% for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer. Conclusion: This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.
|
|
| 10. |
- Lindmark, F, et al.
(författare)
-
Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk
- 2005
-
Ingår i: British Journal of Cancer. - Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden. Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Univ Hosp, Reg Oncol Ctr, Uppsala, Sweden. : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 93:4, s. 493-497
-
Tidskriftsartikel (refereegranskat)abstract
- IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1 alpha and IL1 beta. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case - control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms ( SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe 495% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) ( haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the 'ATGC' haplotype revealed that homozygous carriers were at significantly increased risk ( odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2 - 2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype ( OR = 1.0, 95% CI = 0.8 - 1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI = 1.3 - 2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.
|
|
