Kari Hemminki

German Cancer Research Center | DKFZ · Division of Molecular Genetic Epidemiology

Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and haematological cancers, but its role as a risk factor for MM need to be further explored. Here, we...

Background:Genome-wide association studies (GWAS) of multiple myeloma (MM) in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g. colorectum and melanoma), risk loci have also been associated with patient survival. Methods:We explored the possible association of all the known risk variants...

The role of genetic variation in autophagy-related genes in modulating autophagy and cancer is poorly understood. Here, we comprehensively investigated the association of autophagy-related variants with colorectal cancer (CRC) risk and provide new insights about the molecular mechanisms underlying the associations. After meta-analysis of the genome...

Background: The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. Results: In a pooled analysis of cohort stu...

Estimating familial cancer risks is clinically important in being able to discriminate between individuals in the population at differing risk of malignancy. To gain insight into the familial risk of the different hematological malignancies and their possible inter-relationship, we analyzed data on over 16 million individuals from the Swedish Famil...

Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genet...

Background: Survival rates are increasing in patients with prostate cancer, and second primary cancers (SPCs) are becoming more common in these patients. However, the etiology and clinical consequences of SPCs are not well-known. We define the impact of family history on SPC and causes of mortality in these patients. Patients and methods: A nati...

Background Malignant melanoma (MM) patients are at increasing risk of developing second primary cancers (SPCs). We assessed mortality and risk of SPCs in MM patients with siblings or parents affected with same cancer compared with that of the general population. Methods We used the Swedish Family-Cancer Database to assess relative risks (RRs) and...

Background: Recent identification of 10 germline variants predisposing to monoclonal gammopathy of undetermined significance (MGUS) explicates genetic dependency of this asymptomatic precursor condition with multiple myeloma (MM). Yet much of genetic burden as well as functional links remain unexplained. We propose a workflow to expand the search...

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide...

Population‐based data on metastatic patterns are lacking because cancer registries seldom record metastases. This study uses a novel population‐based approach to identify metastases and describes metastatic pathways from 14 common primary cancers to 12 specific metastatic sites. A total of 179 581 patients with metastatic cancer were identified fro...

Ovarian cancer is a heterogeneous disease. Data regarding familial risks for specific proband, age at diagnosis and histology are limited. Such data can assist genetic counseling and help elucidate etiologic differences among various histologic types of ovarian malignancies. By using the Swedish Family-Cancer Database, we calculated relative risks...

To assess etiological and clinical consequences of second primary cancers (SPCs) in prostate cancer (PC) patients, we followed newly diagnosed patients to identify men who were diagnosed with a SPC and recorded their causes of death. We used the Swedish Family‐Cancer Database to assess relative risks (RRs) and causes of death in SPCs until the year...

Background: With improving survival in ovarian cancer, second primary cancers (SPCs) and their etiological foundations are becoming an issue. The ways in which family history may influence the occurrence of SPCs and the related mortality are not well known. Methods: Based on the Swedish Family-Cancer Database, we identified 11,300 ovarian cancer...

Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses. It is unlikely that prior therapyis solely responsible for SPC risk. To investigate risk of SPC after diagnosis of non-Hodgkin lymphoma (NHL) and 10 of itssubtypes we conducted a novel bidirectional analysis, SPCs after NHL and NHL as SPC. Using the Swedish...

To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of seven genome-wide association studies totalling 5,325 HL cases and 22,423 controls. We identify five new HL risk loci at 6p21.31 (rs649775, P = 2.11 × 10-10), 6q23.3 (rs1002658, P = 2.97 × 10-8), 11q23.1 (rs7111520, P = 1.44 × 10-11),...

Objective: We aimed to explore the effect of occupation on familial risk of pleural mesothelioma in a nationwide cohort study design. Method: The nationwide Swedish Family-Cancer Database includes all Swedes born after 1931 and their biological parents, totalling 16.1 million individuals with about 2.3 million cancer patients. Hazards ratios (HR...

Background Familial clustering of upper gastrointestinal (UGI) cancers and the significance of family history has been addressed previously. We aimed to elucidate the familial risk based on the specified tumor location and histology. Method In the Swedish Family-Cancer Database, we determined the familial risk of UGI cancer patients diagnosed (195...

Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992-2013) to...

Background: Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients. Methods: Following a systematic literature...

Background Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognised by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflam...

[This corrects the article DOI: 10.1371/journal.pone.0174995.].

Whole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred to as FCVPPv2, including 12 tools for evaluating deleteriousness and 5 intolerance scores for missense variants....

Familial risk of ovarian cancer is well-established but whether ovarian cancer clusters with other cancers and the clusters differ by histology remains uncertain. Using data from the Swedish Family-Cancer Database, we explored familial associations of ovarian cancer with other cancers with a novel approach; relative risk for (histology-specific) ov...

Background: Although advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers-ie, develop...

Familial risks for testicular cancer (TC) are among the highest of all cancers. However, data are limited for histological types of TC and for possible familial associations of TC with other cancers. We used the nationwide Swedish Family-Cancer Database for years 1958 to 2015 to analyse familial relative risks (RR) for 11,138 TC patients when first...

Background: Borderline ovarian tumors (BOTs) are a subgroup of ovarian malignancies with low malignant potential. Very limited earlier data are available on familial clustering of BOTs with other cancers. We aim to explore histology-specific familial associations among BOTs and associations between BOT and any invasive cancers. Methods: Based on...

Background: According to the literature the three stone diseases, sialolithiasis (SL), urolithiasis (UL) and cholelithiasis (CL) share comorbidities. We assess familial and spouse risks between these stone disease and compare them to familial risks for concordant (same) stone disease. Methods: Study population including familiar relationships wa...

Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their associ...

(Table A) Complete list of genotyped SNPs in candidate genes, with information about all linked missense SNPs (r2 ≥ 0.8) and the location in protein domains. NMD: nonsense mediated decay; * Variant Effect Predictor by Ensembl http://www.ensembl.org/Homo_sapiens/Tools/VEP (Table B) Population Description. a Z statistics: Wilcoxon Rank-Sum-Test; b Ch...

(Figure A) mRNA expression of NLRP5 (MATER) in CRC. (DOCX)

Introduction With improving survival in ovarian cancer, second primary cancers (SPCs) and their etiological underpinnings are becoming an issue. How family history may influence the occurrence of SPCs and the related mortality is not well known. We defined familial cancer through identity of cancer in the first-degree relatives (parents or siblings...

Background: Family risks for urinary tract cancers (excluding kidney cancers) are known, but less is known about whether rare urinary tract cancer subtypes are also familial and if urinary tract cancers share familial risk for other (discordant) cancers. Objective: To investigate the impact of family history on urinary tract cancers (Internation...

Introduction Multiple myeloma (MM) is a plasma cell dyscrasia characterised by proliferation of monoclonal plasma cells. As one of the most prevalent haematological malignancies, MM is genetically heterogeneous. Although 17 individual MM susceptibility loci have been identified, their inherent biological mechanism is sparsely understood. We carried...

Chronic kidney disease (CKD) patients are characterized by the presence of high levels of DNA damage, and a poor response to ionizing radiation. In this study, we proposed that variants in GST genes could explain this fact. One-hundred twenty seven CKD patients and one-hundred forty five controls constituted the studied groups. Micronuclei (MN) fre...

Background: NLRC5 is an interferon γ-inducible protein, which plays a role in immune surveillance with a potential influence on cancer survival. Objective: We aimed to evaluate the effect of potential regulatory variants in NLRC5 on overall survival and survival after 5-fluorouracil (5-FU)-based therapy of colorectal cancer (CRC) patients. Pati...

Human malignancies are often hallmarked with genomic instability, which itself is also considered a causative event in malignant transformation. Genomic instability may manifest itself as genetic changes in the nucleotide sequence of DNA, or as structural or numerical changes of chromosomes. Unrepaired or insufficiently repaired DNA double-strand b...

Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10-27; βcombine...

Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for...

Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for...

[This corrects the article DOI: 10.1371/journal.pgen.1006866.].

Urolithiasis (UL, urinary tract stone disease) has been reported to increase subsequent cancers in the urinary tract. Recently, we showed data that surveillance bias may be an important confounder in the reported associations. In the present approach we want to address the question of possible cancer risk posed by UL mechanistically. Both UL and ca...