Familial clustering of lung cancer (LC) is related to shared smoking habits but the contribution of other potential factors such as sex or histology is not well known, and these are the subjects of the present study in Sweden. Family relationships (from Multigeneration register) and diagnosed cancers (from Cancer registry) were obtained from the national registers from 1961 to 2021. The overall familial risk for LC was constant from the 1990s but the male familial risk decreased while the female familial risk doubled at the same time when female incidence doubled. The female familial risk for mother-daughter pairs was higher (SIR = 2.2 [2.0-2.3], N = 716) than for father-son pairs (SIR = 1.6 [1.5-1.8], N = 962). The histology-specific familial risks for adenocarcinoma, squamous cell carcinoma, small cell and large cell carcinoma were highest for concordant histology but also present for discordant histology. The number of family members diagnosed with LC was a strong determinant of familial risk. The novel results showed that familial risk of LC depends on the background incidence of LC and is higher for women compared to men. We demonstrated further an increased familial risk for each of the four histological types of LC which was higher for concordant than discordant histologies but was even detected between discordant histologies suggesting that LC histology is not a genetic trait.

• Keywords
• adenocarcinoma, age of onset, incidence trend, proband, sibling risk,
• MeSH
• Adenocarcinoma epidemiology   pathology   MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Incidence MeSH
• Middle Aged MeSH
• Humans MeSH
• Lung Neoplasms * epidemiology   pathology   genetics   MeSH
• Registries statistics & numerical data   MeSH
• Risk Factors MeSH
• Aged MeSH
• Sex Factors MeSH
• Carcinoma, Squamous Cell epidemiology   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Sweden epidemiology   MeSH

A double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to identify novel CRC susceptibility genes, we whole-exome sequenced germline DNA from nine persons with a double primary CRC and a family history of CRC. The detected variants were processed by bioinformatics filtering and prioritization, including STRING protein-protein interaction and pathway analysis. A total of 150 missense, 19 stop-gain, 22 frameshift and 13 canonical splice site variants fulfilled our filtering criteria. The STRING analysis identified 20 DNA repair/cell cycle proteins as the main cluster, related to genes CHEK2, EXO1, FAAP24, FANCI, MCPH1, POLL, PRC1, RECQL, RECQL5, RRM2, SHCBP1, SMC2, XRCC1, in addition to CDK18, ENDOV, ZW10 and the known mismatch repair genes. Another STRING network included extracellular matrix genes and TGFβ signaling genes. In the nine whole-exome sequenced patients, eight harbored at least two candidate DNA repair/cell cycle/TGFβ signaling gene variants. The number of families is too small to provide evidence for individual variants but, considering the known role of DNA repair/cell cycle genes in CRC, the clustering of multiple deleterious variants in the present families suggests that these, perhaps jointly, contributed to CRC development in these families.

• Keywords
• familial colorectal cancer, germline variant, multiple primaries, whole‐exome sequencing,
• MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Colorectal Neoplasms * genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Repair genetics   MeSH
• Pedigree MeSH
• Exome Sequencing MeSH
• Aged MeSH
• Germ-Line Mutation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Germline genetic susceptibilities of rare cancers of the esophagus, stomach, small intestine, testis, (nonmedullary) thyroid gland and bone with high familial risks are not well known. Here, we use familial risk data from the Swedish Family-Cancer Database which contains records of cancers in Swedish families obtained over a century. We compare familial risks for offspring diagnosed with any of these cancers when their parent had or had not that cancer. We review the global literature of the reported constitutional variants that may explain part of the familial risk. MAIN BODY: Familial risks for esophageal and stomach cancers are about 2.0 and apart from early-onset stomach cancer few high-risk variants are known. Genetic studies may be hampered by dominant environmental risk factors for these cancers. Small intestinal carcinoids have a very high familial risk (28 between siblings) but no high-risk genes have been identified to explain this. Low-risk polygenic variants have been identified. Small intestinal adenocarcinoma is a manifestation in Lynch syndrome. Testicular and thyroid cancers are characterized by high familial risk (about 5) which may be explained largely by a polygenic background, although thyroid cancer is a component in a number of rare cancer syndromes. Several predisposing genes have been identified for bone cancer (familial risk 7). CONCLUSIONS: The discussed cancers are rare and they present with a relatively high familial risk, in spite of lacking identified high-penetrant constitutional variants. It is possible that the polygenic component, already recognized for testis cancer, is stronger than previously expected. Thus polygenic models with rare high/moderate- and low-risk variants could fit the familial risk and shape the germline genetic landscape of these cancers. Polygenic background may have clinical implications.

• Keywords
• Constitutional variants, Familial risk, Germline genetics, Heredity,
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: The Swedish Family-Cancer Database (FCD) is the largest source of data on familial cancer in the world, including practically complete family structures and individual cancer diagnoses from the high-quality cancer registry. We present a novel application of FCD by analyzing age-specific familial risks and interpreting them through likely causes, such as germline pathogenic variants and/or environmental exposures. MAIN BODY: The basic assumption for this approach is that a discrete familial clustering in a narrow age-interval is not random but may provide causal clues. For this analysis we selected reasonably common cancers to meaningfully scrutinize familial risk through adulthood in which cancers are diagnosed, that included colorectal (CRC) and endometrial cancers, prostate and kidney cancers and breast and lung cancers. The interpretation is based on the literature. The highest familial relative risks for CRC and endometrial cancers were found at ages 40-44 years, matching the peak impact of mismatch repair gene mutations. However endometrial cancer showed also a small early onset component which could not be explained. Age-related familial risks for breast, prostate and kidney cancers also matched data from large-scale sequencing; these included the early onset component in kidney cancer which was likely due to VHL mutations. Age distribution of familial lung cancer was unique in showing a wide peak extending from middle to old ages, which would be consistent with a combination of direct genetic effects and indirect influence on inheritance of smoking dependence. CONCLUSIONS: The present review of age-specific familial risks and age-of-onset data from the literature may allow an interpretation that the familial and germline landscapes are reasonably harmonious for relatively early onset cancers but at higher ages no discrete peaks can be found which may implicate attenuated impact of high-risk genes and polygenic influence.

• Keywords
• Age of onset, Early onset, Familial risk, Germline genetics, Heredity,
• Publication type
• Journal Article MeSH
• Review MeSH

UNLABELLED: Early recognition of hereditary urological cancers may influence diagnostic and therapeutic decision-making, and potentially alter the fate of patients and family members. Here, we introduce readers to the current knowledge on germline genetic testing and clinical practice in prostate, bladder, renal, and testicular carcinoma. Considering all urological cancer patients, routine inquiries about familial cancer history should become a standard practice in clinical settings. If suspicion arises, patients can opt for two avenues: referral to genetic counseling or undergoing genetic tests after consultation with the treating urologist. PATIENT SUMMARY: Tumors of the urogenital tract (prostate, kidney, bladder, and testes) can sometimes be related to genetic mutations that are present in all the cells of the body. Such mutations can be inherited and run in families. Therefore, it is relevant to obtain information on the incidence of all cancers in the family history. The information obtained may initiate genetic testing, leading to the identification of mutations that are related to cancer in the current or next generation. In addition, these mutations may offer alternative treatment options for patients.

• Keywords
• Genetic, Germline testing, Hereditary cancer, Prostate cancer, Renal cancer, Syndromes, Testicular cancer, Urothelial tract cancer,
• Publication type
• Journal Article MeSH

INTRODUCTION: Thyroid cancer (TC) is diagnosed in several histological types which differ in their clinical characteristics and survival. We aim to describe how they influence TC survival in Sweden. METHODS: Cancer data were obtained from the Swedish cancer registry between years 1999 and 2018, and these were used to analyze relative survival. RESULTS: Relative survival for all TC improved when analyzed in 10-year periods, and female survival improved more than male survival. Female survival advantage appeared to be present also for specific histological types, although case numbers were low for rare types. Female 5-year relative survival for TC was 100% for follicular, 95.1% for oncocytic, 93.4% for papillary, 89.7% for medullary, and 6.1% for anaplastic cancer. Among the clinical TNM classes, only T4 and M1 stages were associated with decreased survival compared to T1-3 and M0. Anaplastic cancer presented most often at high T and M1 stages, in contrast to other TC. Curiously, the diagnostic age for anaplastic M1 patients was lower than that for M0 patients. Both anaplastic and medullary cancers did not show age-dependent increases in the probability of metastases, in contrast to the main histological types. This could indicate the presence of several types of anaplastic and medullary cancers. CONCLUSION: The poor survival for anaplastic TC is an extreme contrast to the excellent survival of differentiated TC. As less than 20% of anaplastic cancer patients survived one year, urgent diagnosis and initiation of treatment are important. Facilitated treatment pathways have been instituted in Denmark resulting in improved survival. Anaplastic cancer should be a target of a major research focus.

• Keywords
• anaplastic cancer, metastasis, prognosis, relative survival, trends,
• Publication type
• Journal Article MeSH

BACKGROUND: Despite treatment having improved through intensive surgical procedures and chemotherapy-and more recently, targeted therapies-ovarian cancer is the most fatal female cancer. As such, we wanted to analyze age-specific survival trends for ovarian cancer in Denmark, Finland, Norway and Sweden over the past 50 years, with a special aim of comparing survival development between the age groups. METHODS: We modelled survival data from the NORDCAN database for 1-, 5- and conditional 5/1-year relative (between years 1 and 5) survival for ovarian cancer from 1972 to 2021. RESULTS: Young patients had a 70% 5-year survival while the survival was only 30% for the oldest patients. Conditional survival showed that survival between years 1 and 5 did not improve for patients older than 60 years throughout the 50-year period, during which time the gaps between the youngest and the oldest patients widened. CONCLUSIONS: Improvement in 1-year survival was so large that it masked the modest development between years 1 and 5, resulting in a widening age disparity in 5-year survival. The current treatment practices, which appear increasingly effective for younger patients, have not helped remedy the large age differences in ovarian cancer survival. Early detection methods and therapeutic innovations are urgently needed, and aged patients need a special focus.

• Keywords
• carboplatin cancer control, prognosis, relative survival, treatment,
• Publication type
• Journal Article MeSH

BACKGROUND: Female cancers cover common breast cancers, relatively common endometrial, ovarian, and cervical cancers and rare vulvar cancer. Survival in these cancers is known to be relatively good compared to all cancers but long-term studies for these cancers are rare, and to fill the gap, here, we generate survival data through 50 years. MATERIALS AND METHODS: We applied generalized additive models to data from the NORDCAN database and analyzed 1- and 5-year relative survival for these cancers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over half a century (1971-2020). Conditional 5/1-year survival for patients who survived the 1st year after diagnosis and annual survival changes was also estimated. RESULTS: In 2016-20, 5-year survival was best for breast cancer reaching 92.3% (in SE), followed by endometrial cancer at 86.1% (SE) and cervical cancer at 75.6% (NO). Improvement in 5-year survival over the 50 years was the largest for ovarian cancer (20% units), finally reaching 52.9% (SE). For vulvar cancer, the final survival was between 70 and 73%. The best 5-year survival rate in 2016-20 was recorded for SE in breast, endometrial, and ovarian cancers; NO showed the highest rate for cervical and DK for vulvar cancers. DK had the lowest survival for breast and ovarian cancers, and FI, for the other cancers. CONCLUSIONS: The overall survival development appeared to consist of continuous improvements, most likely because of novel treatment and imaging techniques as well as overall organization of patient care. The large survival improvement for ovarian cancer was probably achieved by a surgical focus on tumors spread in the peritoneal cavity. For cervical and vulvar cancers, the high early mortality requires attention and could be helped by raising increasing public awareness of early symptoms in these cancers and developing pathways for fast initiation of treatment.

• Publication type
• Journal Article MeSH

Kidney and bladder cancers share etiology and relatively good recent survival, but long-term studies are rare. We analyzed survival for these cancers in Denmark, Finland, Norway (NO), and Sweden (SE) over a 50-year period (1971-2020). Relative 1- and 5-year survival data were obtained from the NORDCAN database, and we additionally calculated conditional 5/1-year survival. In 2016-2020, 5-year survivals for male kidney (79.0%) and bladder (81.6%) cancers were best in SE. For female kidney cancer, NO survival reached 80.0%, and for bladder cancer, SE survival reached 76.1%. The magnitude of 5-year survival improvements during the 50-year period in kidney cancer was over 40% units; for bladder cancer, the improvement was over 20% units. Survival in bladder cancer was worse for women than for men, particularly in year 1. In both cancers, deaths in the first year were approximately as many as in the subsequent 4 years. We could document an impressive development for kidney cancer with tripled male and doubled female 5-year survival in 50 years. Additionally, for bladder cancer, a steady improvement was recorded. The current challenges are to curb early mortality and target treatment to reduce long-term mortality.

• Keywords
• conditional survival, relative survival, surgery, treatment, uro-oncology,
• Publication type
• Journal Article MeSH

BACKGROUND: Gastric cancer (GC) and esophageal cancer (EC) are among the most fatal cancers and improving survival in them is a major clinical challenge. Nordic cancer data were recently released up to year 2019. These data are relevant for long-term survival analysis as they originate from high-quality national cancer registries from countries with practically free access to health care, thus documenting 'real-world' experience for entire populations. PATIENTS/METHODS: Data were obtained for Danish (DK), Finnish (FI), Norwegian (NO), and Swedish (SE) patients from the NORDCAN database from years 1970 through 2019. Relative 1- and 5-year survival were analyzed, and additionally the difference between 1- and 5-year survival was calculated as a measure of trends between years 1 and 5 after diagnosis. RESULTS: Relative 1-year survival for Nordic men and women in GC was 30% in period 1970-74 and it increased close to 60%. Early 5-year survival ranged between 10 and 15% and the last figures were over 30% for all women and NO men while survival for other men remain below 30%. Survival in EC was below that in GC, and it reached over 50% for 1-year survival only for NO patients; 5-year survival reached over 20% only for NO women. For both cancers, the difference between 1- and 5-year survival increased with time. Survival was worst among old patients. CONCLUSION: GC and EC survival improved over the 50-year period but the increase in 5-year survival was entirely explained by gains in 1-year survival, which improved at an accelerated pace in EC. The likely reasons for improvements are changes in diagnosis, treatment, and care. The challenges are to push survival past year 1 with attention to old patients. These cancers have a potential for primary prevention through the avoidance of risk factors.

• Keywords
• mortality, relative survival, risk factors, stomach cancer, treatment,
• MeSH
• Incidence MeSH
• Humans MeSH
• Survival Rate MeSH
• Esophageal Neoplasms * epidemiology   therapy   MeSH
• Stomach Neoplasms * epidemiology   therapy   MeSH
• Registries MeSH
• Risk Factors MeSH
• Age Distribution MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Denmark MeSH
• Scandinavian and Nordic Countries epidemiology   MeSH