Objective: In the era of genome‐wide association studies, familial risks are used to estimate disease heritability and the likelihood of candidate‐gene identification. This study was undertaken to estimate associations of rheumatoid arthritis (RA) with any of 33 autoimmune diseases and related conditions among parents and offspring, singleton siblings, twins, and spouses.Methods: The Multigeneration Register in Sweden was used as a reliable source of information on Swedish families throughout the last century. Data on autoimmune diseases in individual family members were obtained through linkage to the Hospital Discharge Register. The standardized incidence ratio (SIR) was calculated as a measure of the relative risk of RA in family members of patients with RA or any of 33 other autoimmune diseases or related conditions, as compared with the relative risk of RA in those lacking an affected family member.Results: Among a total of 447,704 patients, 47,361 were diagnosed as having RA. The SIRs for RA were 3.02 in offspring of affected parents, 4.64 in siblings, 9.31 in multiplex families, 6.48 in twins, and 1.17 in spouses. Significant associations with the familial risk of RA in offspring according to parental proband were observed for ankylosing spondylitis (SIR 2.96), localized scleroderma (SIR 2.40), Sjögren's syndrome (SIR 2.25), systemic lupus erythematosus (SIR 2.13), systemic sclerosis (SIR 1.65), Hashimoto thyroiditis/hypothyroidism (SIR 1.54), pernicious anemia (SIR 1.53), sarcoidosis (SIR 1.40), psoriasis (SIR 1.36), Wegener's granulomatosis (SIR 1.34), and asthma or polymyalgia rheumatica (SIR 1.32).Conclusion: This is the first study to compare the familial risks of RA in relation to a large number of autoimmune diseases and related conditions using data from a single population. The high discordant familial risks in this population suggest that there is extensive genetic sharing between RA and the associated diseases.

Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10⁻⁸), 6q21 (rs9372120, P=9.09 × 10⁻¹⁵), 7q36.1 (rs7781265, P=9.71 × 10⁻⁹), 8q24.21 (rs1948915, P=4.20 × 10⁻¹¹), 9p21.3 (rs2811710, P=1.72 × 10⁻¹³), 10p12.1 (rs2790457, P=1.77 × 10⁻⁸), 16q23.1 (rs7193541, P=5.00 × 10⁻¹²) and 20q13.13 (rs6066835, P=1.36 × 10⁻¹³), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.

The present article summarizes recent developments in the characterization of genetic predisposition to colorectal cancer (CRC). The main themes covered include new hereditary CRC and polyposis syndromes, non-CRC hereditary cancer genes found mutated in CRC patients, strategies used to identify novel causal genes, and review of candidate genes that have been proposed to predispose to CRC and/or colonic polyposis. We provide an overview of newly described genes and syndromes associated with predisposition to CRC and polyposis, including: polymerase proofreading-associated polyposis, NTHL1-associated polyposis, mismatch repair gene biallelic inactivation-related adenomatous polyposis (including MSH3- and MLH3-associated polyposes), GREM1-associated mixed polyposis, RNF43-associated serrated polyposis, and RPS20 mutations as a rare cause of hereditary nonpolyposis CRC. The implementation of next generation sequencing approaches for genetic testing has exposed the presence of pathogenic germline variants in genes associated with hereditary cancer syndromes not traditionally linked to CRC, which may have an impact on genetic testing, counseling and surveillance. The identification of new hereditary CRC and polyposis genes has not deemed an easy endeavor, even though known CRC-related genes explain a small proportion of the estimated familial risk. Whole-genome sequencing may offer a technology for increasing this proportion, particularly if applied on pedigree data allowing linkage type of analysis. The final section critically surveys the large number of candidate genes that have been recently proposed for CRC predisposition.

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 from the Swedish Cancer Registry and metastatic sites were identified using the Cause of Death Register and the National Patient Register. Patterns of metastatic spread were described across age and sex. In men, colorectal cancer was the main source of lung, peritoneal, and liver metastases. Lung cancer was the main origin of pleural and nervous system metastases. Prostate cancer dominated bone metastases but had minor contribution to other metastatic sites. Among women, breast cancer was the dominant origin of most metastatic sites, with the exception of peritoneum which was ruled by metastases from the ovary. As other exceptions, for nervous system metastases, lung cancer was the origin of metastases somewhat more frequently than breast cancer and for liver metastases, colorectal cancer was the main origin instead of breast cancer. The present achievement was to implement the first nationwide description of clinical landscape of cancer metastases, with an aim to serve as a reliable source for clinicians and researchers.

Objectives.: Cancer and type 2 diabetes (T2D) are two common diseases that may share risk factors. We aimed at determining subsequent cancer risks in patients hospitalized for T2D in Sweden. Methods.: T2D patients were obtained from the nationwide Hospital Discharge Register; cancers were recorded from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for cancer following last hospitalization for T2D. The comparison group was the general Swedish population. Results.: The number of hospitalized T2D patients from 1964 to 2007 was 125,126, of whom 26,641 had an affected family member. Altogether 24 cancers showed an elevated risk when follow-up was started after the last hospitalization. The highest SIRs were for pancreatic (6.08) and liver (4.25) cancers. The incidences of these cancers were even elevated when follow-up was started 5 years after the last hospitalization for T2D, with primary liver cancer showing the highest SIR of 4.66. Also increased were the incidences of upper aerodigestive tract, esophageal, colon, rectal, pancreatic, lung, cervical, endometrial, ovarian, and kidney cancers. Prostate cancer showed a lower risk. Familial T2D patients showed no exceptional elevated cancer risks but their prostate cancer and melanoma risks were lower. Conclusions.: This study, covering approximately one half of Swedish T2D patients, showed an elevated risk for several cancers after hospitalization for T2D, probably indicating the profound metabolic disturbances of the underlying disease. The highest risks were found for liver and pancreatic cancers. No excess cancer risks were observed in familial diabetics. The lower risk for prostate cancer remains intriguing.