Publications by authors named "Janne Pitkäniemi"

115 Publications

Risk of induced abortions in childhood cancer survivors.

Cancer 2021 Jan 25. Epub 2021 Jan 25.

Institute for Statistical and Epidemiological Cancer Research, Finnish Cancer Registry, Helsinki, Finland.

Background: The relative probability of pregnancy and parenthood in cancer survivors is reduced. Studies have shown that cancer survivors are concerned about the health of their offspring and the recurrence of their own cancer. This could lead to an increased risk of induced abortion. The aim of this study was to examine whether pregnancies of childhood cancer survivors (CCSs) who were 0 to 14 years old at diagnosis in 1971-2012 were more likely to result in induced abortions in comparison with population controls.

Methods: Data from Finnish registries for cancer, births, and induced abortions were merged to identify 420 first pregnancies of CCSs and 2508 first pregnancies of age-matched population controls in 1987-2013. Poisson regression and logistic regression modeling were used to estimate incidence rates and relative risks (RRs) with 95% confidence intervals (CIs) of first pregnancies and induced abortions in CCSs in comparison with population controls.

Results: The risk of first pregnancy was reduced in CCSs in comparison with population controls (RR, 0.72; 95% CI, 0.64-0.80), whereas the risk of a first pregnancy resulting in an induced abortion was similar in CCSs and population controls (RR, 1.01; 95% CI, 0.77-1.33). In subanalyses stratifying by decade of diagnosis and cancer treatment, the risk of induced abortion was similar in CCSs and population controls.

Conclusions: Female CCSs do not have an overall increased risk of induced abortions. The reduced probability of pregnancy among CCSs highlights the continued need for interventions to preserve fertility at the time of a cancer diagnosis.
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http://dx.doi.org/10.1002/cncr.33384DOI Listing
January 2021

Educational inequalities and regional variation in colorectal cancer survival in Finland.

Cancer Epidemiol 2021 Feb 24;70:101858. Epub 2020 Nov 24.

Finnish Cancer Registry, Unioninkatu 22, 00130 Helsinki, Finland; Department of Public Health, University of Helsinki, Yliopistonkatu 3, 00014 Helsinki, Finland; Faculty of Social Sciences, University of Tampere, Kuntokatu 3, 33520 Tampere, Finland.

Background: Previous studies have reported lower colorectal cancer (CRC) survival in patients with low compared to high educational levels. We investigated the impact of education on CRC survival by using both individual and area-based information on education.

Methods: Patients diagnosed with CRC in Finland in 2007-2016 were followed up for death until the end of 2016. Age-standardized relative survival and relative excess risk of death (RER) were estimated by sex using period approach. RERs were adjusted for age, stage at diagnosis, cancer site, urbanity, hospital district and municipality by using Bayesian piecewise constant excess hazard models. Analyses were conducted including individual (basic, secondary, high) and area-based (quartiles Q1-Q4 based on the proportion of population with basic education) education separately as well as both measures in one model.

Results: We analysed in all 24 462 CRC patients. There was a clear gradient in 5-year relative survival across education groups (men: basic 62 %, secondary 64 %, high 69 %; women: basic 61 %, secondary 67 %, high 71 %). Compared to the basic education group, RER in the high education group was significantly lower. This association was still present after including area-based education in the models (men: RER 0.72, 95 % Confidence interval (CI) 0.64-0.81; women: RER 0.76, 95 % CI 0.59-0.96). Area-based education revealed smaller effect estimates than individual education in CRC survival and no association for men.

Conclusion: Individual education information should be preferred over area-based when survival differences are studied by education. Educational differences in CRC survival are still present in Finland.
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http://dx.doi.org/10.1016/j.canep.2020.101858DOI Listing
February 2021

Cancer Incidence and Mortality in the Oldest Old: a Nationwide Study in Finland.

Am J Epidemiol 2020 Oct 22. Epub 2020 Oct 22.

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

The world's population is aging rapidly. This study reports the burden of cancer in the oldest old (≥85 years) in Finland in 1953-2017 and estimates age-specific cancer rates in the old population (65-99 years) in 1988-2017. The Finnish Cancer Registry provided data on all cancer diagnoses, cancer deaths and other deaths in cancer patients in Finland in 1953-2017. Between 1953-1957 and 2013-2017, the proportion of incident cancers in those aged ≥85 years increased from 1.5% to 9.6% (597 to 15,360 new cases), and in 2013-2017, more new cancers were diagnosed at age ≥85 years than age <50 years. Cancer incidence and excess mortality attributable to cancer peaked at age 85-94 years and declined subsequently, whereas cancer-specific mortality continued to increase or plateaued. Due to demographic changes, the number of new cancers in the oldest old has increased substantially in Finland, and currently, nearly one in 10 cancers are diagnosed in this age group. The increasing cancer burden in the oldest old poses a major challenge for healthcare and needs to be addressed in designing clinical research and reporting of cancer registries. In old populations with competing risks of death, we propose excess cancer mortality as a measure of cancer-related mortality.
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http://dx.doi.org/10.1093/aje/kwaa236DOI Listing
October 2020

Familial aggregation of testicular cancer among early-onset cancer survivors. A prospective observational cohort data from Finland.

Cancer Epidemiol 2020 Dec 10;69:101807. Epub 2020 Oct 10.

Finnish Cancer Registry, Unioninkatu 22, 00130 Helsinki, Finland; School of Health Sciences, University of Tampere, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland. Electronic address:

Testicular cancer (TC) is the most common form of cancer in men aged 15-35 years. Familial risk for TC is among highest of all cancers.

Material And Methods: A prospective observational cohort of 9111 relatives in 2,188 families of early-onset TC patients, called probands, diagnosed at age ≤40 years in Finland between 1970 and 2012. Standardized incidence ratios (SIR) were used as measures of familial aggregation for early-onset (≤40 years) TC. Follow-up ended at diagnosis of TC, death or 31 December 2014 whichever earliest.

Results: Among first-degree relatives of early-onset TCs, in all 12 early-onset TC cases (0.24%) were diagnosed over the follow-up; the SIR for any first-degree relative was 4.59 (95% confidence interval (CI): 2.37-8.01) and for brothers the SIR was 6.51 (95% CI 3.12-11.96).

Discussion: Familial aggregation of TC shows substantial risk for early-onset TC among first-degree relatives of early-onset TC patients in Finland. This is important to acknowledge to avoid diagnostic delay especially of TC.
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http://dx.doi.org/10.1016/j.canep.2020.101807DOI Listing
December 2020

Genome-wide landscape establishes novel association signals for metabolic traits in the Arab population.

Hum Genet 2021 Mar 9;140(3):505-528. Epub 2020 Sep 9.

Dasman Diabetes Institute, P.O. Box 1180, 15462, Dasman, Kuwait.

While the Arabian population has a high prevalence of metabolic disorders, it has not been included in global studies that identify genetic risk loci for metabolic traits. Determining the transferability of such largely Euro-centric established risk loci is essential to transfer the research tools/resources, and drug targets generated by global studies to a broad range of ethnic populations. Further, consideration of populations such as Arabs, that are characterized by consanguinity and a high level of inbreeding, can lead to identification of novel risk loci. We imputed published GWAS data from two Kuwaiti Arab cohorts (n = 1434 and 1298) to the 1000 Genomes Project haplotypes and performed meta-analysis for associations with 13 metabolic traits. We compared the observed association signals with those established for metabolic traits. Our study highlighted 70 variants from 9 different genes, some of which have established links to metabolic disorders. By relaxing the genome-wide significance threshold, we identified 'novel' risk variants from 11 genes for metabolic traits. Many novel risk variant association signals were observed at or borderline to genome-wide significance. Furthermore, 349 previously established variants from 187 genes were validated in our study. Pleiotropic effect of risk variants on multiple metabolic traits were observed. Fine-mapping illuminated rs7838666/CSMD1 rs1864163/CETP and rs112861901/[INTS10,LPL] as candidate causal variants influencing fasting plasma glucose and high-density lipoprotein levels. Computational functional analysis identified a variety of gene regulatory signals around several variants. This study enlarges the population ancestry diversity of available GWAS and elucidates new variants in an ethnic group burdened with metabolic disorders.
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http://dx.doi.org/10.1007/s00439-020-02222-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889551PMC
March 2021

Variation in cancer survival between hospital districts and within them in Finland.

Acta Oncol 2020 Nov 18;59(11):1316-1321. Epub 2020 Jun 18.

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

Background: Monitoring regional variation in population-based cancer survival is useful for assessing equity in national health-care system. This study quantifies variation in survival between municipalities and hospital districts responsible for primary care and for specialised care, respectively, in Finland.

Material And Methods: Five-year relative survival of 11 cancers and close to 700,000 patients was estimated by municipality in Finland over 1962-2016 using hierarchical Bayesian modelling. Variation (i) between hospital districts, (ii) between municipalities within hospital districts, and (iii) between all municipalities (total variation) were quantified by the standard deviation of 5-year relative survival standardised by the average survival level.

Results: In 2007-2016, the largest variation in 5-year relative survival between all municipalities was in stomach, prostate, kidney and liver cancer and skin melanoma. In male skin melanoma, prostate, and kidney cancer and in male and female pancreatic cancer, there was substantial and statistically significant variation between hospital districts, too. Variation within hospital districts was on average 67% (95% posterior interval [58%,76%]) out of the total variation and had decreased by 18% [2%, 33%] from 1997-2006.

Conclusion: The decrease in variation within hospital districts suggests that equity in diagnostics and primary care has improved in Finland. However, the variation between hospital districts in skin melanoma, prostate and kidney cancer reflects differences in early diagnostics. In pancreatic cancer, substantial variation between hospital districts may relate to regional differences in the accessibility and the quality of cancer treatments.
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http://dx.doi.org/10.1080/0284186X.2020.1772500DOI Listing
November 2020

Familial cancer risk in family members and spouses of patients with early-onset head and neck cancer.

Head Neck 2020 09 30;42(9):2524-2532. Epub 2020 May 30.

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer and Research, Helsinki, Finland.

Background: Reported patterns of familial aggregation of head and neck cancer (HNC) vary greatly, with many studies hampered by the limited number of subjects.

Methods: Altogether 923 early-onset (≤40 years old) HNC probands, their first-degree relatives, spouses, and siblings' offspring were ascertained. Cumulative risk and standardized incidence ratios (SIRs) were estimated.

Results: Of all early-onset HNC families, only 21 (2.3%) had familial HNC cancers at any age and less than five familial early onset HNC cancers among first-degree relatives. The cumulative risk of HNC for siblings by age 60 (0.52%) was at population level (0.33%). No increased familial risk of early-onset HNC could be discerned in family members (SIR 2.68, 95% CI 0.32-9.68 for first-degree relatives).

Conclusions: Our study indicates that the cumulative and relative familial risk of early-onset HNC is modest in the Finnish population and, at most, only a minor proportion of early-onset HNCs are due solely to inherited genetic mutations.
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http://dx.doi.org/10.1002/hed.26282DOI Listing
September 2020

Linking population-based registries to identify familial cancer risk in childhood cancer.

Cancer 2020 Jul 21;126(13):3076-3083. Epub 2020 Apr 21.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.

Background: Linked population-based registries provide a unique source for identification of new family cancer syndromes and for elucidating risk of early-onset cancer in close relatives of cancer patients.

Methods: Using the Finnish Cancer Registry, we identified 9078 probands who had been diagnosed with cancer at <21 years of age between 1970 and 2012. Siblings, offspring, parents, nephews, and nieces of probands were identified from the Population Registry. Childhood and young adult (ChYA) cancer diagnoses (age 0-39 years) in relatives were identified by linking to the Finnish Cancer Registry. The relative risk of ChYA cancer in family members of probands was estimated using standardized incidence ratios (SIRs).

Results: Among 58,010 family members of the 9078 probands, 363 ChYA cancers were diagnosed, 324 of which were expected (SIR, 1.12; 95% CI, 1.01-1.24). The risk of ChYA cancer was elevated both in offspring (SIR, 2.25; 95% CI, 1.51-3.24) and in siblings (SIR, 1.17; 95% CI, 1.01-1.36). Offspring of probands with retinoblastoma were at highest risk (SIR, 75.85; 95% CI, 32.75-149.45); risks were also elevated for siblings of probands with lymphoma (SIR, 1.62; 95% CI, 1.14-2.25). Known cancer predisposition syndromes were observed in 29 (66%) of 44 sibling pairs with cancers diagnosed at <21 years of age and in 20% of the 135 families with a childhood cancer proband whose sibling was diagnosed with a young adult malignancy.

Conclusion: Linked population-based registry data indicate a modestly increased risk of ChYA in relatives of children with cancer. Some of the observed cancer clusters in the cohort suggest novel patterns and familial cancer syndromes.
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http://dx.doi.org/10.1002/cncr.32882DOI Listing
July 2020

Survival and mortality of elderly men with localized prostate cancer managed with primary androgen deprivation therapy or by primary observation.

BMC Urol 2020 Mar 12;20(1):25. Epub 2020 Mar 12.

Department of Urology, Tampere University Hospital, Tampere, Finland.

Background: Androgen deprivation therapy (ADT) remains a primary treatment for localized prostate cancer (PCa) even though there is no evidence that its use is beneficial in the absence of curative treatment.

Methods: Men aged ≥70 years (n = 16,534) diagnosed with localized PCa from 1985 to 2014 and managed either with primary observation or ADT in the absence of curative treatment were included. The cases were identified from the population-based Finnish Cancer Registry. We estimated the standardized mortality ratios (SMR) for overall mortality by treatment group. We determined the relative risk (RR) of PCa-specific mortality (PCSM) and other-cause mortality between the two treatment groups. Survival was determined using the life table method. Two age groups (70-79 years and ≥ 80 years) and three calendar time cohorts (1985-1994, 1995-2004, and 2005-2014) were compared following adjustment of propensity score matching between the treatment groups with four covariates (age, year of diagnosis, educational level, and hospital district). Follow-up continued until death or until December 31, 2015.

Results: Patients in the observation group had lower overall SMRs than those in the ADT group in both age cohorts over the entire study period. PCSM was higher in men aged 70-79 years undergoing primary ADT compared to those managed by observation only (RR: 1.70, 95% confidence interval [CI]: 1.29-2.23 [1985-1994]; RR 1.55, 95% CI: 1.35-1.84 [1995-2004]; and RR 2.71, 95% CI: 2.08-3.53 [2005-2014]); p = 0.005 for periodic trend. A similar trend over time was also observed in men aged > 80 years; (p for age-period interaction = 0.237). Overall survival was also higher among men in their 70's managed by observation compared to those undergoing ADT.

Conclusions: Primary ADT within four months period from diagnosis is not associated with improved long-term overall survival or decreased PCSM compared to primary conservative management for men with localized PCa. However, this observational study's conclusions should be weighted with confounding factors related to cancer aggressiveness and comorbidities.
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http://dx.doi.org/10.1186/s12894-020-00593-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069023PMC
March 2020

Disparities in glioblastoma survival by case volume: a nationwide observational study.

J Neurooncol 2020 Apr 14;147(2):361-370. Epub 2020 Feb 14.

Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, Topeliuksenkatu 5, P.O. Box 266, 00029, Helsinki, Finland.

Introduction: High hospital case volumes are associated with improved treatment outcomes for numerous diseases. We assessed the association between academic non-profit hospital case volume and survival of adult glioblastoma patients.

Methods: From the nationwide Finnish Cancer Registry, we identified all adult (≥ 18 years) patients with histopathological diagnoses of glioblastoma from 2000 to 2013. Five university hospitals (treating all glioblastoma patients in Finland) were classified as high-volume (one hospital), middle-volume (one hospital), and low-volume (three hospitals) based on their annual numbers of cases. We estimated one-year survival rates, estimated median overall survival times, and compared relative excess risk (RER) of death between high, middle, and low-volume hospitals.

Results: A total of 2,045 patients were included. The mean numbers of annually treated patients were 54, 40, and 17 in the high, middle, and low-volume hospitals, respectively. One-year survival rates and median survival times were higher and longer in the high-volume (39%, 9.3 months) and medium-volume (38%, 8.9 months) hospitals than in the low-volume (32%, 7.8 months) hospitals. RER of death was higher in the low-volume hospitals than in the high-volume hospital (RER = 1.19, 95% CI 1.07-1.32, p = 0.002). There was no difference in RER of death between the high-volume and medium-volume hospitals (p = 0.690).

Conclusion: Higher glioblastoma case volumes were associated with improved survival. Future studies should assess whether this association is due to differences in patient-specific factors or treatment quality.
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http://dx.doi.org/10.1007/s11060-020-03428-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136186PMC
April 2020

Risk of second primary cancer in oral squamous cell carcinoma.

Head Neck 2020 08 14;42(8):1848-1858. Epub 2020 Feb 14.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland.

Background: The incidence and survival of oral squamous cell carcinoma (OSCC) patients have increased in recent years. Understanding their long-term survival aspects is essential for optimal treatment and follow-up planning. Almost one in five cancers diagnosed occurs nowadays in individuals with a previous diagnosis of cancer.

Methods: Patients diagnosed with primary OSCC during 1953-2015 were retrieved from the Finnish Cancer Registry. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population.

Results: Among 6602 first primary OSCC patients there were 640 (10%) SPCs. The SIR for SPCs was 1.85 (95% CI: 1.71-1.99, P < .001) corresponding to an EAR of 8.78 (95% CI: 7.29-10.26).

Conclusions: Health care professionals should be aware of the second primary cancer risk after management of primary OSCC and patients need to be counseled about this phenomenon.
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http://dx.doi.org/10.1002/hed.26107DOI Listing
August 2020

Genome-wide association study identifies novel risk variants from RPS6KA1, CADPS, VARS, and DHX58 for fasting plasma glucose in Arab population.

Sci Rep 2020 01 13;10(1):152. Epub 2020 Jan 13.

Dasman Diabetes Institute, P.O. Box 1180, Dasman, 15462, Kuwait.

Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 (RPS6KA1) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; β-discovery = 8.315; β-replication = 3.442; β-combined = 6.551). Further, three suggestive associations (p-values < 8.2E-06) with high FPG were observed at rs487321 (CADPS), rs707927 (VARS and 2Kb upstream of VWA7), and rs12600570 (DHX58); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology.
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http://dx.doi.org/10.1038/s41598-019-57072-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957513PMC
January 2020

Vasectomy and the risk of prostate cancer in a Finnish nationwide population-based cohort.

Cancer Epidemiol 2020 02 21;64:101631. Epub 2019 Nov 21.

Department of Urology, Turku University Hospital, Turku, Finland, Department of Urology, University of Turku, Turku, Finland Kiinamyllynkatu 4-8, 20100, Turku, Finland. Electronic address:

Introduction & Objectives: There are conflicting reports on the association of vasectomy and the risk of prostate cancer (PCa). Our objective was to evaluate the association between vasectomy and PCa from a nationwide cohort in Finland.

Materials & Methods: Sterilization registry of Finland and the Finnish Cancer Registry data were utilized to identify all men who underwent vasectomy between years 1987-2014 in Finland. Standard incidence ratio (SIR) for PCa as well as all-cause standardized mortality ratios (SMR) were calculated.

Results: We identified 38,124 men with vasectomy with a total of 429,937 person-years follow-up data. The median age at vasectomy was 39.7 years (interquartile range [IQR] 35.9-44.0), after vasectomy PCa was diagnosed in 413 men (122 cases 0-10 years, 219 cases 10-20 years and 72 cases >20 years from vasectomy). SIR for PCa for the vasectomy cohort was 1.15 (95% CI: 1.04-1.27). By the end of follow-up, 19 men had died from PCa, while the expected number was 20.5 (SMR 0.93 [95%CI: 0.56-1.44]). The overall mortality was decreased (SMR 0.54 [95%CI: 0.51-0.58]) among men with vasectomy.

Conclusion: We found a small statistically significant increase in PCa incidence after vasectomy, but in contrast the mortality of vasectomized men was significantly reduced. This may be due to higher likelihood of vasectomized men to undergo prostate-specific antigen testing, having healthier general lifestyle and other biological factors e.g. high reproductive fitness.
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http://dx.doi.org/10.1016/j.canep.2019.101631DOI Listing
February 2020

Maternal diabetes and risk of childhood cancer in the offspring.

Int J Cancer 2020 08 27;147(3):662-668. Epub 2019 Nov 27.

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

An association between maternal diabetes, its medication and childhood cancer has not been previously explored in a registry-based setting. With a case-control design, we aimed to explore whether maternal diabetes is associated with an increased risk of childhood cancer in the offspring. Combining data from population-based registries, we analyzed a total of 2,029 cases, that is, persons with childhood cancer diagnosed under the age of 20 years between years 1996-2014 and a total of 10,103 matched population controls. The mothers of the cases/controls and their diagnoses of diabetes (DM) before/during pregnancy as well as their insulin/metformin prescriptions during pregnancy were identified. Conditional logistic regression modeling was used to analyze the risk of childhood cancer. The OR for childhood cancer among those exposed to any maternal diabetes was 1.32 (95% CI 1.14-1.54) compared to the offspring of the nondiabetic mothers. The effect of maternal diabetes on the risk of childhood cancer remained elevated even after adjusting for maternal age, parity and smoking. Our data suggest that maternal diabetes medication may reduce the risk for childhood cancer (adjusted OR 0.83, 95% CI 0.36-1.94), especially in gestational diabetes (adjusted OR 0.26, 95% CI 0.05-1.25), compared to the diabetic mothers without medication. The risk of childhood leukemia was significantly higher among children exposed to any maternal diabetes (OR 1.36, CI 1.04-1.77) compared to the unexposed. Maternal diabetes appears to be associated with an increased risk of childhood cancer in the offspring. The possible risk-reducing effect of an exposure to diabetes medication on offspring cancer risk warrants further investigation.
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http://dx.doi.org/10.1002/ijc.32757DOI Listing
August 2020

Trends of colorectal cancer incidence by education and socioeconomic status in Finland.

Acta Oncol 2019 Nov 22;58(11):1557-1563. Epub 2019 Aug 22.

Finnish Cancer Registry, Helsinki, Finland.

The aim of this study was to investigate if the incidence of colorectal cancer (CRC) is associated with education and socioeconomic status (SES) in Finland, and if there are any changes in incidence differences between the groups over the period 1976-2014. CRC cases ( = 77,614) were retrieved from the Finnish Cancer Registry and linked with information on the education level and SES from Statistics Finland. We used Poisson regression model to quantify differences in incidence rates between the groups, and to assess changes over calendar time. Colon cancer incidence was higher among the highly educated, than in those with basic education. Similar differences were observed by SES in men. Incidence rates increased steeply over time among men with basic education (from 16.7/100,000 in 1976-1979 to 31.8 in 2010-2014), resulting in narrowed differences between the groups ( < .001). Incidence trends of proximal and distal colon and rectal cancer in men showed similar patterns. Heterogeneity across time periods by SES was observed only in colon cancer incidence in men ( = .009). No such large differences were detected in women. Steep increase in colon cancer incidence in men with basic education, and the respective persistent high incidence in the highly educated highlights the importance of focusing the preventive measures on modifiable lifestyle factors in order to reduce CRC incidence and to narrow the educational and socioeconomic health differences.
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http://dx.doi.org/10.1080/0284186X.2019.1652340DOI Listing
November 2019

Childhood cancer mortality and survival in immigrants: A population-based registry study in Finland.

Int J Cancer 2020 05 24;146(10):2746-2755. Epub 2019 Aug 24.

Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Helsinki University Hospital, Helsinki, Finland.

Immigration in Europe has increased considerably over the past decades with the immigrant population similarly expanding in Finland. Our aim was to study childhood cancer mortality and survival in immigrants. In all, 4,437 patients diagnosed with cancer under the age of 20 years between 1990 and 2009 were identified from the Finnish Cancer Registry and their parents from the Population Register Center. Information on demographic factors was obtained from Statistics Finland. Poisson regression modeling was used to estimate hazard ratios (HRs) for cancer deaths. The life table method and the log rank test were used in survival analysis. Patients or parents of foreign background and born abroad had higher 5-year mortality (patient HR 2.03, 95% CI 1.18-3.49; maternal HR 2.11, 95% CI 1.46-3.04; paternal HR 1.85, 95% CI 1.29-2.66) compared to those of Finnish background and born in Finland. Childhood cancer survival in 5-year follow-up was higher if the mother (83% vs. 68%) or the father (83% vs. 70%) were of Finnish background and born in Finland. Despite equal access to public health care, we observed significant differences in childhood cancer mortality and survival by background. Cultural differences, linguistic obstacles and difficulties in navigating the health care system may contribute, along with genetic and biologic factors. Offering tailored information and taking cultural and linguistic aspects into account is necessary when diagnosing and treating patients from different ethnic backgrounds who have not yet integrated into the local culture and health care system.
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http://dx.doi.org/10.1002/ijc.32625DOI Listing
May 2020

Familial aggregation of early-onset cancers.

Int J Cancer 2020 04 27;146(7):1791-1799. Epub 2019 Jun 27.

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

This registry-linkage study evaluates familial aggregation of cancer among relatives of a population-based series of early-onset (≤40 years) cancer patients in Finland. A cohort of 376,762 relatives of early-onset cancer patients diagnosed between 1970 and 2012 in 40,538 families was identified. Familial aggregation of early-onset breast, colorectal, brain and other central nervous system (CNS) cancer and melanoma was explored by standardized incidence ratios (SIR), stratified by relatedness. Gender-, age- and period-specific population cancer incidences were used as reference. Cumulative risks for siblings and offspring of the proband up to age ≤40 years were also estimated. Almost all early-onset cancers were sporadic (98% or more). Among first-degree relatives, SIR was largest in colorectal cancer (14, 95% confidence interval 9.72-18), and lowest in melanoma (1.93, 1.05-3.23). Highest relative-specific SIRs were observed for siblings in families, where also parent had concordant cancer, 90 (43-165) for colorectal cancer and 29 (11-64) for CNS cancer. In spouses, all SIRs were at population level. Cumulative risk of colorectal cancer by age 41 was 0.98% in siblings and 0.10% in population, while in breast cancer the corresponding risks were 2.05% and 0.56%. In conclusion, early-onset cancers are mainly sporadic. Findings support high familial aggregation in early-onset colorectal and CNS cancers. Familial aggregation in multiplex families with CNS cancers was mainly attributed to neurofibromatosis and in colorectal cancer to FAP- and HNPCC-syndromes. The pattern of familial aggregation of early-onset breast cancer could be seen to support very early exposure to environmental factors and/or rare genetic factors.
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http://dx.doi.org/10.1002/ijc.32512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027840PMC
April 2020

Use of fertility drugs in early-onset female cancer survivors-A Finnish register-based study on 8,929 survivors.

Int J Cancer 2020 02 29;146(3):829-838. Epub 2019 Apr 29.

Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Advances in multimodality cancer treatments have increased the risk of long-term complications in early-onset cancer survivors. For female cancer survivors, these include diminished reproductive function, often resulting in a narrowed fertile window. The aim of our study was to evaluate the use of fertility treatments in cancer survivors (aged 0-39 years at diagnosis) compared to siblings. Data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8,929 survivors and 9,495 siblings without previous deliveries. Fertility drug purchases from 1993 to 2012 at the age of 16-41 years were included. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for the use of fertility drugs, adjusting for age and calendar time at fertility drug purchase. Fertility treatments were more common in survivors compared to siblings, as 6.1% of survivors compared to 3.8% of siblings had bought fertility drugs (IRR 1.43, 95% confidence interval [CI] 1.25-1.65). A subclassification of fertility treatments into ovulation inductions and assisted reproductive technology (ART), showed increased use of ART (IRR 2.41, 95% CI 1.97-2.96), whereas the use of ovulation induction was similar in survivors and siblings. Analyses by calendar time periods showed the use of ART to be significantly higher in the most recent decade, from 2003 onwards. We conclude that cancer survivors have an increased risk for subfertility, which is why fertility counseling is important. However, our results mirror a more active approach among clinicians towards fertility treatments in cancer survivors during the most recent years.
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http://dx.doi.org/10.1002/ijc.32346DOI Listing
February 2020

Correction: Association of symptoms and interval breast cancers in the mammography-screening programme: population-based matched cohort study.

Br J Cancer 2019 Apr;120(7):773-774

Mass Screening Registry, Finnish Cancer Registry, FI-00130, Helsinki, Finland.

The authors report that the labels indicating the symptom types and no symptom lines in the original version of Figure 2 were missing. The correct version of Figure 2 with the labels included is provided below.
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http://dx.doi.org/10.1038/s41416-019-0417-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461836PMC
April 2019

Pediatric malignancies in neurofibromatosis type 1: A population-based cohort study.

Int J Cancer 2019 12 18;145(11):2926-2932. Epub 2019 Feb 18.

Institute of Biomedicine, University of Turku, Turku, Finland.

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population-based cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patients <20 years of age. Persons born in 1987-2011 were included, and 524 persons were followed through the files of the Finnish Cancer Registry from birth up to age 20 years. This amounted to 8,376 person years. Fifty-three patients had cancer <20 years of age, yielding a standardized incidence ratio (SIR) of 35.6. The most frequent location of pediatric cancers was the central nervous system (CNS); there were 45 cases and the SIR was 115.7. Exclusion of 22 optic pathway gliomas (OPGs) gave an SIR of 59.1 for the CNS and 21.6 for all cancers. There were nine malignant peripheral nerve sheath tumors (MPNSTs); their cumulative risk was 2.7% by age 20. No cases of leukemia were observed. NF1 patients showed considerable excess mortality with a standardized mortality ratio (SMR) of 73.1. The survival of NF1 patients with CNS tumors other than OPGs did not differ from that of non-NF1 controls (HR 0.64, 95% CI 0.23 to 1.76). In conclusion, brain tumors in childhood and MPNSTs in adolescence are malignancies of major concern in patients with NF1. The risk for myeloid malignancies may not be as high as suggested in the literature.
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http://dx.doi.org/10.1002/ijc.32187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849871PMC
December 2019

Cancer incidence and mortality patterns in women with breast symptoms in the mammography screening programme: A matched cohort analysis.

Int J Cancer 2019 06 11;144(12):2928-2935. Epub 2019 Jan 11.

Mass Screening Registry, Finnish Cancer Registry, Helsinki, Finland.

Efforts to reduce mortality through early detection and diagnosis has intensified in the recent decade. An important risk factor, 'breast symptoms' reported by women during screening visit, remains overlooked. In this population based matched cohort study using Finnish National Breast Cancer Screening Program (FNBCSP), we assessed the association between breast symptoms reported at screening visit and the risk of cancer incidence and breast cancer mortality and all-cause mortality followed-up over a period of 24 years. For each visit with symptoms, non-symptomatic controls were matched (1:1 for lump and retraction; 1:2 for nipple discharge) based on age at screening visit, year of invitation, number of invited visits, and municipality of invitation. Women who reported lump or retraction had about two-fold risk of breast cancer incidence, three-fold risk of breast cancer mortality and all-cause mortality respectively as compared to women without respective symptoms (p-value<0.05). We found a substantial difference (p-value<0.05) in mortality rates throughout the follow-up period between symptomatic and asymptomatic group. In absolute terms, after the follow-up period for women who reported lump, 180 died from breast cancer as compared to 70 deaths in those without lump, per 10,000 person-years of follow-up, and 315 versus 160 all-cause deaths per 10,000 person-years in women with and without lump respectively. our study provides comprehensive evidence that women with breast symptoms remain in a higher risk of dying over a very long period. The findings indicate needs to develop improvements in the guidelines for screening and clinical services for women presenting with symptoms.
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http://dx.doi.org/10.1002/ijc.32035DOI Listing
June 2019

Association of symptoms and interval breast cancers in the mammography-screening programme: population-based matched cohort study.

Br J Cancer 2018 11 7;119(11):1428-1435. Epub 2018 Nov 7.

Mass Screening Registry, Finnish Cancer Registry, FI-00130, Helsinki, Finland.

Background: We assessed the association between symptoms reported at breast cancer screening visits and interval cancers (ICs) in a prospective manner.

Methods: This population-based matched cohort study uses data of the Finnish National Breast Cancer Screening Programme that invites women aged 50-69 years old during 1992-2012. Subjects who attended screening with symptoms were matched with asymptomatic reference cohorts based on age at screening visit, year of invitation, number of invited visits and municipality of invitation. The primary outcome was ICs.

Results: Women with a lump had a threefold (hazard ratio 3.7, 95% confidence interval (CI) 3.0-4.6) risk of ICs and a higher risk (hazard ratio 1.7, 95% CI 1.4 to 2.0) at the subsequent visit compared with those without a lump. The fatal interval cancer risk increased by 0.39 per 1000 screens with a lump. The cumulative incidences of interval cancer increased within a month of a mammography-negative visit with a lump and after about 6 months of the visit with retraction or nipple discharge.

Conclusion: Women with breast symptoms have a clearly increased risk of interval breast cancer after the screening visit. Our findings indicate the need for different screening strategies in symptomatic women.
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http://dx.doi.org/10.1038/s41416-018-0308-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265247PMC
November 2018

Estimating multilevel regional variation in excess mortality of cancer patients using integrated nested Laplace approximation.

Stat Med 2019 02 17;38(5):778-791. Epub 2018 Oct 17.

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

Models of excess mortality with random effects were used to estimate regional variation in relative or net survival of cancer patients. Statistical inference for these models based on the Markov chain Monte Carlo (MCMC) methods is computationally intensive and, therefore, not feasible for routine analyses of cancer register data. This study assessed the performance of the integrated nested Laplace approximation (INLA) in monitoring regional variation in cancer survival. Poisson regression model of excess mortality including both spatially correlated and unstructured random effects was fitted to the data of patients diagnosed with ovarian and breast cancer in Finland during 1955-2014 with follow up from 1960 through 2014 by using the period approach with five-year calendar time windows. We estimated standard deviations associated with variation (i) between hospital districts and (ii) between municipalities within hospital districts. Posterior estimates based on the INLA approach were compared to those based on the MCMC simulation. The estimates of the variation parameters were similar between the two approaches. Variation within hospital districts dominated in the total variation between municipalities. In 2000-2014, the proportion of the average variation within hospital districts was 68% (95% posterior interval: 35%-93%) and 82% (60%-98%) out of the total variation in ovarian and breast cancer, respectively. In the estimation of regional variation, the INLA approach was accurate, fast, and easy to implement by using the R-INLA package.
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http://dx.doi.org/10.1002/sim.8010DOI Listing
February 2019

Glioblastoma survival is improving despite increasing incidence rates: a nationwide study between 2000 and 2013 in Finland.

Neuro Oncol 2019 02;21(3):370-379

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

Background: We assessed population-level changes in glioblastoma survival between 2000 and 2013 in Finland, with focus on elderly patients (>70 y) in order to assess if changes in treatment of glioblastoma are reflected also in population-based survival rates.

Methods: We identified all patients (age ≥18 y) from the Finnish Cancer Registry (FCR) with a histopathological diagnosis of primary glioblastoma in 2000-2013. Patients were followed up until December 2015. The accuracy of register-based search of glioblastoma patients was internally validated. We report age-standardized relative survival ratios and relative excess risks (RERs) of death in 2000-2006 (pre-period) and 2007-2013 (post-period).

Results: We identified 2045 glioblastoma patients from the FCR. The accuracy of the FCR-based search was 97%. Median age was 63.3 years, and 42% were women. Incidence increased on average by 1.6% (P = 0.004) and median age by 0.4 years per calendar year. Between the pre- and post-periods, the proportion of patients >70 years increased from 24% to 27%. In >70-year-old patients, the median survival time increased from 3.6 months in 2000-2006 to 4.5 months in 2007-2013 (RER 0.82, 95% CI: 0.68-0.98). In ≤70-year-old patients, the median survival time increased from 9.3 months in 2000-2006 to 11.7 months in 2007-2013 (RER 0.74, 95% CI: 0.67-0.82).

Conclusion: Despite the increased proportion of elderly glioblastoma patients, population-level survival of glioblastoma patients has improved since the year 2000. However, increasing incidence, increasing age of patients, and poor survival in elderly are alarming, and future studies should perhaps focus more on elderly.
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http://dx.doi.org/10.1093/neuonc/noy164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380416PMC
February 2019

On Exploring Hidden Structures Behind Cervical Cancer Incidence.

Cancer Control 2018 Jan-Dec;25(1):1073274818801604

1 Department of Mathematics and Systems Analysis, Aalto University School of Science, Espoo, Finland.

Finding new etiological components is of great interest in disease epidemiology. We consider time series version of invariant coordinate selection (tICS) as an exploratory tool in the search of hidden structures in the analysis of population-based registry data. Increasing cancer burden inspired us to consider a case study of age-stratified cervical cancer incidence in Finland between the years 1953 and 2014. The latent components, which we uncover using tICS, show that the etiology of cervical cancer is age dependent. This is in line with recent findings related to the epidemiology of cervical cancer. Furthermore, we are able to explain most of the variation of cervical cancer incidence in different age groups by using only two latent tICS components. The second tICS component, in particular, is interesting since it separates the age groups into three distinct clusters. The factor that separates the three clusters is the median age of menopause occurrence.
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http://dx.doi.org/10.1177/1073274818801604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156216PMC
April 2019

Anxiety and pain during bone marrow aspiration and biopsy.

Scand J Pain 2012 Apr 1;3(2):92-96. Epub 2012 Apr 1.

Department of Anaesthesiology and Intensive Care Medicine, University of Helsinki, Helsinki Finland.

Background Previously we found that pre-procedural nervousness and tension (translated into English as "anxiety"), assessed on a non-validated five-point scale, correlated with pain intensity of the various stages of bone marrow aspiration and biopsy (BMAB). The fewer the previous BMAB procedures the stronger the pain from a repeated procedure. The primary purpose of the present observational study is to evaluate the state of anxiety just before BMAB and to find out whether it affects the pain experiences during the various stages of the BMAB procedure. We also examined whether first-timers differ from patients with previous BMAB experience in the degree of anxiety and intensity of BMAB procedural pain. Methods A total of 166 adult outpatients undergoing the BMAB from the Helsinki University Hospital were enrolled, 48 of them being first-timers. The level of anxiety was measured with State-Trait Anxiety Inventory (STAI) and the pain experiences associated with the various stages of the procedure were evaluated on the NRS-scale (Numeral Rating Scale 0-10) and using the Finnish pain vocabulary. BMAB was planned to be performed under lidocaine infiltration anaesthesia but, on request, patients were allowed to receive premedication with diazepam orally or alfentanil i.m. If, in spite of supplemental local anaesthetic the patient still felt pain from the sampling needle tip, i.m. alfentanil was administered. Results There was a clear association between anxiety and pain during all stages of the procedure, except during biopsy. The NRS scores varied from 0 to 10 in all the various stages of BMAB. The first-timers did not differ from the more experienced patients with regard to pain experiences; only the pain felt during the local anaesthetic infiltration was milder (P = 0.007) in first-timers than in the others. Procedural pain in those who were given analgesic or sedative premedication was similar (P < 0.05) to that in the non-premedicated patients. The words characterizing the pain of the various stages belonged to a major extent (76-90%) to the sensory class of words. Conclusion Pre-procedural anxiety had a major impact on the pain ratings. The first-timers and patients with previous experience of BMAB had a similar degree of pre-procedural anxiety, as well as of the intensity of procedural pain, except that infiltration of local anaesthetic was less painful in the first-timers. Implications Identification of anxious (fearful) patients prior to BMAB, and premedicating them individually may improve satisfaction in both patient and caregiver.
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http://dx.doi.org/10.1016/j.sjpain.2011.11.002DOI Listing
April 2012

Impact of parental socioeconomic factors on childhood cancer mortality: a population-based registry study.

Acta Oncol 2018 Nov 4;57(11):1547-1555. Epub 2018 Jun 4.

a Finnish Cancer Registry , Helsinki , Finland.

Introduction: Parental socioeconomic status has been proposed to have an influence on childhood cancer mortality even in high-income countries. Our study investigated the influence of parental socioeconomic factors on childhood cancer mortality.

Material And Methods: We identified 4437 patients diagnosed with cancer under the age of 20 from 1990 to 2009 and their parents from the Finnish cancer and central population registers. Information on death from primary cancer during five-year follow-up and parental socioeconomic factors was obtained from Statistics Finland. Poisson regression modeling was used to estimate hazard ratios (HRs) for factors related to cause-specific mortality and recursive tree based survival analysis to identify important risk factors and interactions.

Results: Mortality was lower in the highest quartile of combined parental disposable income (HR 0.68, CI 95% 0.52-0.89) compared to the lowest quartile. In the most recent diagnostic period from 2000 to 2009, highest attained education of either parent being post-secondary predicted lower mortality (HR 0.73, CI 95% 0.60-0.88) compared to parents who had attained primary or lower education.

Conclusion: Despite high quality public health care and comprehensive social security, both high parental income and education were associated with lower mortality after childhood cancer. Lower health literacy and financial pressures limiting treatment adherence may explain higher mortality in children with less educated parents and parents with lower income. Motivation and support during treatment and follow-up period is needed concerning the families of these patients.
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http://dx.doi.org/10.1080/0284186X.2018.1478125DOI Listing
November 2018

The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland.

Int J Cancer 2018 03 31;142(5):891-898. Epub 2017 Oct 31.

Department of Urology, Turku University Hospital, Turku, Finland, Department of Urology, University of Turku, Turku, Finland.

Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three-tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68 versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994 and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10-year post-PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post-PSA period.
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http://dx.doi.org/10.1002/ijc.31109DOI Listing
March 2018

Second primary cancer after major salivary gland carcinoma.

Head Neck 2018 02 29;40(2):251-258. Epub 2017 Sep 29.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: We investigated the risk of second primary cancers after major salivary gland carcinoma in Finland, with a population of 5.5 million.

Methods: Nationwide cancer registry data were used to identify patients with major salivary gland carcinoma diagnosed between 1953 and 2014. Standardized incidence ratios (SIRs) were estimated to compare their second primary cancer risk with the respective site-specific cancer risk in the general population.

Results: There were 1727 patients with major salivary gland carcinomas and 222 second primary cancers had been diagnosed in these patients (SIR 1.43). The risk was increased for cancers of the thyroid (SIR 5.12), breast (SIR 1.63), respiratory organs (SIR 1.63), male genital organs (SIR 1.48), melanoma of the skin (SIR 3.35), and nonmelanoma skin cancer (SIR 2.50). The risk was high during the first 5 years and after 20 years of diagnosis.

Conclusion: Second primary cancers can occur among patients with major salivary gland carcinoma even after a long time period. This needs to be recognized in the follow-up of these patients.
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http://dx.doi.org/10.1002/hed.24937DOI Listing
February 2018