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Supplementary Table 1. This is a table of all mutations found the four InvTCC tumors, there positions, and genotype quality scores.

Supplementary Tables 2 and 3. Listing genotypes and clinical data.

Background: Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of Bernese Mountain Dogs (BMD).Methods: Genomic DNA was collected from affected and unaffected BMD in North America and Europe. Both independent and combined genome-wide association studies (GWAS) were used to identify cancer-associated loci. Fine mapping and sequencing narrowed the primary locus to a single gene region.Results: Both populations shared the same primary locus, which features a single haplotype spanning MTAP and part of CDKN2A and is present in 96% of affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in several types of cancer.Conclusions: We present the first GWAS for histiocytic sarcoma in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data show the power of studying distinctive malignancies in highly predisposed dog breeds.Impact: Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight about this cancer-associated, complex, and poorly understood genomic region. Cancer Epidemiol Biomarkers Prev; 21(7); 1019–27. ©2012 AACR.

Supplementary Table 1 from Expression of SLCO Transport Genes in Castration-Resistant Prostate Cancer and Impact of Genetic Variation in SLCO1B3 and SLCO2B1 on Prostate Cancer Outcomes

Background: Mismatch repair (MMR) gene activity may be associated with prostate cancer risk and outcomes. This study evaluated whether single nucleotide polymorphisms (SNP) in key MMR genes are related to prostate cancer outcomes.Methods: Data from two population-based case-control studies of prostate cancer among Caucasian and African-American men residing in King County, Washington were combined for this analysis. Cases (n = 1,458) were diagnosed with prostate cancer in 1993 to 1996 or 2002 to 2005 and were identified through the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. Controls (n = 1,351) were age-matched to cases and were identified through random digit dialing. Logistic regression was used to assess the relationship between haplotype-tagging SNPs and prostate cancer risk and disease aggressiveness. Cox proportional hazards regression was used to assess the relationship between SNPs and prostate cancer recurrence and prostate cancer–specific death.Results: Nineteen SNPs were evaluated in the key MMR genes: five in MLH1, 10 in MSH2, and 4 in PMS2. Among Caucasian men, one SNP in MLH1 (rs9852810) was associated with overall prostate cancer risk [odds ratio, 1.21; 95% confidence interval (95% CI), 1.02, 1.44; P = 0.03], more aggressive prostate cancer (odds ratio, 1.49; 95% CI, 1.15, 1.91; P < 0.01), and prostate cancer recurrence (hazard ratio, 1.83; 95% CI, 1.18, 2.86; P < 0.01), but not prostate cancer–specific mortality. A nonsynonymous coding SNP in MLH1, rs1799977 (I219V), was also found to be associated with more aggressive disease. These results did not remain significant after adjusting for multiple comparisons.Conclusion: This population-based case-control study provides evidence for a possible association with a gene variant in MLH1 in relation to the risk of overall prostate cancer, more aggressive disease, and prostate cancer recurrence, which warrants replication. Cancer Epidemiol Biomarkers Prev;19(1); OF1–7

Background: Chronic inflammation is an important mechanism for the development and progression of prostate cancer (PC). To better understand the potential relationship between genes in the inflammation pathway and PC risk, we evaluated variants in 16 candidate genes.Methods: A total of 143 tagging and amino acid altering single nucleotide polymorphisms (SNPs) were genotyped in Caucasian and African American men participating in one of two population-based, case–control studies (n = 1,458 cases and 1,351 controls). The relative risk of PC was estimated using logistic and polytomous regression models.Results: Ten SNPs in seven genes (CXCL12, IL4, IL6, IL6ST, PTGS2, STAT3, and TNF) were nominally associated (P < 0.05) with risk of PC in Caucasians. The most significant effect on risk was seen with rs11574783 in the interleukin 6 signal transducer (IL6ST) gene (OR = 0.08, 95% CI: 0.01–0.63). Cumulatively, four SNPs in genes interleukin 4 (IL4), IL6ST, PTGS2, and signal transducer and activator of transcription 3 (STAT3) conferred a three-fold elevation in PC risk among men carrying the maximum number of high-risk alleles (OR = 2.97, 95% CI: 1.41–6.25, Ptrend = 0.0003). Risk estimates for seven SNPs varied significantly according to disease aggressiveness (Phomogeneity < 0.05), with SNPs in AKT1, PIK3R1, and STAT3 independently associated with more aggressive PC; OR = 5.1 (95% CI: 2.29–11.40, Ptrend = 3.8 × 10−5) for carriers of all high-risk genotypes.Conclusions: These results suggest that variants in genes within the inflammation pathway may play a role in the development of PC, however, further studies are needed to replicate our findings.Impact: These results underline the potential importance of the inflammation pathway in PC development and progression. Cancer Epidemiol Biomarkers Prev; 20(5); 923–33. ©2011 AACR.

Background: Metastases from men with castration-resistant prostate cancer (CRPC) harbor increased tumoral androgens versus untreated prostate cancers. This may reflect steroid uptake by OATP (organic anion transporting polypeptide)/SLCO transporters. We evaluated SLCO gene expression in CRPC metastases and determined whether prostate cancer outcomes are associated with single nucleotide polymorphisms (SNP) in SLCO2B1 and SLCO1B3, transporters previously shown to mediate androgen uptake.Methods: Transcripts encoding eleven SLCO genes were analyzed in untreated prostate cancer and in metastatic CRPC tumors obtained by rapid autopsy. SNPs in SLCO2B1 and SLCO1B3 were genotyped in a population-based cohort of 1,309 Caucasian prostate cancer patients. Median survival follow-up was 7.0 years (0.77–16.4). The risk of prostate cancer recurrence/progression and prostate cancer–specific mortality (PCSM) was estimated with Cox proportional hazards analysis.Results: Six SLCO genes were highly expressed in CRPC metastases versus untreated prostate cancer, including SLCO1B3 (3.6-fold; P = 0.0517) and SLCO2B1 (5.5-fold; P = 0.0034). Carriers of the variant alleles SLCO2B1 SNP rs12422149 (HR: 1.99; 95% CI: 1.11–3.55) or SLCO1B3 SNP rs4149117 (HR: 1.76; 95% CI: 1.00–3.08) had an increased risk of PCSM.Conclusions: CRPC metastases show increased expression of SLCO genes versus primary prostate cancer. Genetic variants of SLCO1B3 and SLCO2B1 are associated with PCSM. Expression and genetic variation of SLCO genes which alter androgen uptake may be important in prostate cancer outcomes.Impact: OATP/SLCO genes may be potential biomarkers for assessing risk of PCSM. Expression and genetic variation in these genes may allow stratification of patients to more aggressive hormonal therapy or earlier incorporation of nonhormonal-based treatment strategies. Cancer Epidemiol Biomarkers Prev; 20(4); 619–27. ©2011 AACR.

Supplementary Table 1 from Genetic Polymorphisms in Inflammation Pathway Genes and Prostate Cancer Risk

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