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  1. Article ; Online: Long-term risk of cancer among the first-degree relatives of epithelial ovarian cancer patients: A cohort study with 48 years of follow up.

    Kotaniemi-Talonen, Laura / Pukkala, Eero / Aittomäki, Kristiina / Auranen, Annika

    Acta obstetricia et gynecologica Scandinavica

    2023  Volume 102, Issue 3, Page(s) 240–245

    Abstract: Introduction: The long-term risk of cancer among first-degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are ... ...

    Abstract Introduction: The long-term risk of cancer among first-degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers.
    Material and methods: Using registry data, we conducted a retrospective cohort study with a total of 6501 first-degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach).
    Results: The overall number of cancers was not increased among the first-degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27-2.79), mostly explained by a 2.30-fold (95% CI 1.46-3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient.
    Conclusions: In our study cohort, we did not observe an increase in the overall cancer risk among the first-degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives.
    MeSH term(s) Female ; Humans ; Male ; Breast Neoplasms ; Carcinoma, Ovarian Epithelial/epidemiology ; Carcinoma, Ovarian Epithelial/genetics ; Cohort Studies ; Follow-Up Studies ; Genes, BRCA1 ; Genetic Predisposition to Disease ; Ovarian Neoplasms/epidemiology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Retrospective Studies ; Risk Factors ; Disease Susceptibility
    Language English
    Publishing date 2023-01-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80019-3
    ISSN 1600-0412 ; 0001-6349
    ISSN (online) 1600-0412
    ISSN 0001-6349
    DOI 10.1111/aogs.14504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Pathogenic Variant Spectrum in Breast Cancer Risk Genes in Finnish Patients.

    Nurmi, Anna K / Suvanto, Maija / Dennis, Joe / Aittomäki, Kristiina / Blomqvist, Carl / Nevanlinna, Heli

    Cancers

    2022  Volume 14, Issue 24

    Abstract: Recurrent pathogenic variants have been detected in several breast and ovarian cancer (BC/OC) risk genes in the Finnish population. We conducted a gene-panel sequencing and copy number variant (CNV) analysis to define a more comprehensive spectrum of ... ...

    Abstract Recurrent pathogenic variants have been detected in several breast and ovarian cancer (BC/OC) risk genes in the Finnish population. We conducted a gene-panel sequencing and copy number variant (CNV) analysis to define a more comprehensive spectrum of pathogenic variants in
    Language English
    Publishing date 2022-12-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14246158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Other short opinions/comments on moderate/low cancer genetic risk markers in medical practice and the article Genetic contribution to all cancers

    Aittomäki Kristiina

    Hereditary Cancer in Clinical Practice , Vol 6, Iss 2, Pp 67-

    the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology by Lubinski et al., Breast Cancer Res Treat 2008 Apr 15

    2008  Volume 68

    Keywords Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Language English
    Publishing date 2008-06-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Other short opinions/comments on moderate/low cancer genetic risk markers in medical practice and the article Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology by Lubinski et al., Breast Cancer Res Treat 2008 Apr 15.

    Aittomäki, Kristiina

    Hereditary cancer in clinical practice

    2008  Volume 6, Issue 2, Page(s) 67–68

    Language English
    Publishing date 2008-06-15
    Publishing country Poland
    Document type Journal Article
    ZDB-ID 2252512-9
    ISSN 1897-4287 ; 1731-2302
    ISSN (online) 1897-4287
    ISSN 1731-2302
    DOI 10.1186/1897-4287-6-2-67
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Long-term health of women with genetic POI due to FSH-resistant ovaries.

    Luiro, Kaisu / Aittomäki, Kristiina / Jousilahti, Pekka / Tapanainen, Juha S

    Endocrine connections

    2019  Volume 8, Issue 10, Page(s) 1354–1362

    Abstract: Objective: To study the use of hormone therapy (HT), morbidity and reproductive outcomes of women with primary ovarian insufficiency (POI) due to FSH-resistant ovaries (FSHRO).: Design: A prospective follow-up study in a university-based tertiary ... ...

    Abstract Objective: To study the use of hormone therapy (HT), morbidity and reproductive outcomes of women with primary ovarian insufficiency (POI) due to FSH-resistant ovaries (FSHRO).
    Design: A prospective follow-up study in a university-based tertiary clinic setting.
    Methods: Twenty-six women with an inactivating A189V FSH receptor mutation were investigated by means of a health questionnaire and clinical examination. Twenty-two returned the health questionnaire and 14 were clinically examined. Main outcome measures in the health questionnaire were reported as HT, morbidity, medication and infertility treatment outcomes. In the clinical study, risk factors for cardiovascular disease (CVD) and metabolic syndrome (MetS) were compared to age-matched controls from a national population survey (FINRISK). Average number of controls was 326 per FSHRO subject (range 178-430). Bone mineral density and whole-body composition were analyzed with DXA. Psychological and sexual well-being was assessed with Beck Depression Inventory (BDI21), Generalized Anxiety Disorder 7 (GAD-7) and Female Sexual Function Index (FSFI) questionnaires.
    Results: HT was initiated late (median 18 years of age) compared with normal puberty and the median time of use was shorter (20-22 years) than the normal fertile period. Osteopenia was detected in 9/14 of the FSHRO women despite HT. No major risk factors for CVD or diabetes were found.
    Conclusions: HT of 20 years seems to be associated with a similar cardiovascular and metabolic risk factor profile as in the population control group. However, optimal bone health may require an early-onset and longer period of HT, which would better correspond to the natural fertile period.
    Language English
    Publishing date 2019-09-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2668428-7
    ISSN 2049-3614
    ISSN 2049-3614
    DOI 10.1530/EC-19-0244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Constitutional mosaicism for a BRCA2 mutation as a cause of early-onset breast cancer.

    Alhopuro, Pia / Vainionpää, Reetta / Anttonen, Anna-Kaisa / Aittomäki, Kristiina / Nevanlinna, Heli / Pöyhönen, Minna

    Familial cancer

    2020  Volume 19, Issue 4, Page(s) 307–310

    Abstract: Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast and ovarian cancer syndrome (HBOC). Mutations in these genes are usually inherited, and reports of de novo BRCA1/2 mutations are rare. To date, only one patient with low-level BRCA1 ... ...

    Abstract Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast and ovarian cancer syndrome (HBOC). Mutations in these genes are usually inherited, and reports of de novo BRCA1/2 mutations are rare. To date, only one patient with low-level BRCA1 mutation mosaicism has been published. We report on a breast cancer patient with constitutional somatic mosaicism of a BRCA2 mutation. BRCA2 mutation c.9294C>G, p.(Tyr3098Ter) was detected in 20% of reads in DNA extracted from peripheral blood using next-generation sequencing (NGS). The BRCA2 mutation was subsequently observed at similar levels in normal breast tissue, adipose tissue, normal right fallopian tube tissue and ovaries of the patient, suggesting that this mutation occurred early in embryonic development. This is the first case to report constitutional mosaicism for a BRCA2 mutation and shows that BRCA2 mosaicism can underlie early-onset breast cancer. NGS for BRCA1/2 should be considered for patients whose tumors harbor a BRCA1/2 mutation and for individuals suggestive of genetic predisposition but without a family history of HBO.
    MeSH term(s) Adult ; Age of Onset ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Papillary/genetics ; Carcinoma, Papillary/pathology ; Codon ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Mosaicism ; Mutation, Missense ; Nonsense Mediated mRNA Decay
    Chemical Substances Codon
    Language English
    Publishing date 2020-05-28
    Publishing country Netherlands
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1502496-9
    ISSN 1573-7292 ; 1389-9600
    ISSN (online) 1573-7292
    ISSN 1389-9600
    DOI 10.1007/s10689-020-00186-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: NTHL1 is a recessive cancer susceptibility gene.

    Nurmi, Anna K / Pelttari, Liisa M / Kiiski, Johanna I / Khan, Sofia / Nurmikolu, Mika / Suvanto, Maija / Aho, Niina / Tasmuth, Tiina / Kalso, Eija / Schleutker, Johanna / Kallioniemi, Anne / Heikkilä, Päivi / Aittomäki, Kristiina / Blomqvist, Carl / Nevanlinna, Heli

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 21127

    Abstract: In search of novel breast cancer (BC) risk variants, we performed a whole-exome sequencing and variant analysis of 69 Finnish BC patients as well as analysed loss-of-function variants identified in DNA repair genes in the Finns from the Genome ... ...

    Abstract In search of novel breast cancer (BC) risk variants, we performed a whole-exome sequencing and variant analysis of 69 Finnish BC patients as well as analysed loss-of-function variants identified in DNA repair genes in the Finns from the Genome Aggregation Database. Additionally, we carried out a validation study of SERPINA3 c.918-1G>C, recently suggested for BC predisposition. We estimated the frequencies of 41 rare candidate variants in 38 genes by genotyping them in 2482-4101 BC patients and in 1273-3985 controls. We further evaluated all coding variants in the candidate genes in a dataset of 18,786 BC patients and 182,927 controls from FinnGen. None of the variants associated significantly with cancer risk in the primary BC series; however, in the FinnGen data, NTHL1 c.244C>T p.(Gln82Ter) associated with BC with a high risk for homozygous (OR = 44.7 [95% CI 6.90-290], P = 6.7 × 10
    MeSH term(s) Humans ; Female ; Genetic Predisposition to Disease ; Breast Neoplasms/genetics ; Heterozygote ; Breast ; Finland ; Deoxyribonuclease (Pyrimidine Dimer)/genetics
    Chemical Substances NTHL1 protein, human (EC 3.1.25.1) ; Deoxyribonuclease (Pyrimidine Dimer) (EC 3.1.25.1)
    Language English
    Publishing date 2023-11-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-47441-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor.

    Mattila, Kalle E / Mäkelä, Siru / Kytölä, Soili / Andersson, Emma / Vihinen, Pia / Ramadan, Susan / Skyttä, Tanja / Tiainen, Leena / Vuoristo, Meri-Sisko / Tyynelä-Korhonen, Kristiina / Koivunen, Jussi / Kohtamäki, Laura / Aittomäki, Kristiina / Hernberg, Micaela

    Acta oncologica (Stockholm, Sweden)

    2022  Volume 61, Issue 10, Page(s) 1263–1267

    Abstract: Background: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients.: Material and methods: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable ... ...

    Abstract Background: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients.
    Material and methods: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples.
    Results: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis.
    Conclusion: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.
    MeSH term(s) Humans ; Biomarkers ; Biomarkers, Tumor/genetics ; Circulating Tumor DNA/genetics ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/pathology ; Mutation ; Neoplasms, Second Primary ; Prognosis ; Prospective Studies ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins B-raf/genetics
    Chemical Substances Biomarkers ; Biomarkers, Tumor ; BRAF protein, human (EC 2.7.11.1) ; Circulating Tumor DNA ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
    Language English
    Publishing date 2022-10-28
    Publishing country England
    Document type Clinical Trial ; Journal Article
    ZDB-ID 896449-x
    ISSN 1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
    ISSN (online) 1651-226X
    ISSN 0349-652X ; 0284-186X ; 1100-1704
    DOI 10.1080/0284186X.2022.2137693
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Sikiön diagnoosi äidin verestä--kajoamaton kromosomipoikkeavuuksien seulonta.

    Anttonen, Anna-Kaisa / Stefanovic, Vedran / Aittomäki, Kristiina

    Duodecim; laaketieteellinen aikakauskirja

    2015  Volume 131, Issue 22, Page(s) 2083–2088

    Abstract: In Finland, the screening of fetal chromosome aberrations is currently based on combined screening in the first trimester. Non-invasive prenatal testing (NIPT) is a new method enabling a more accurate screening than combined screening of fetal chromosome ...

    Title translation Fetal diagnosis from the mother's blood--noninvasive screening of chromosomal aberrations.
    Abstract In Finland, the screening of fetal chromosome aberrations is currently based on combined screening in the first trimester. Non-invasive prenatal testing (NIPT) is a new method enabling a more accurate screening than combined screening of fetal chromosome aberrations from the mother's blood sample by analyzing cell-free fetal DNA (cffDNA). In addition, it is possible to determine the gender of the fetus or assess the number of sex chromosomes. Although NIPT is an accurate screening method, an aberrant result should always be confirmed by an invasive fetal diagnostic test.
    MeSH term(s) Biomarkers/blood ; Chromosome Aberrations ; Female ; Finland ; Genetic Testing/methods ; Humans ; Mass Screening/methods ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis/methods
    Chemical Substances Biomarkers
    Language Finnish
    Publishing date 2015
    Publishing country Finland
    Document type English Abstract ; Journal Article
    ZDB-ID 127604-9
    ISSN 0012-7183
    ISSN 0012-7183
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Detection of KRAS mutations in liquid biopsies from metastatic colorectal cancer patients using droplet digital PCR, Idylla, and next generation sequencing.

    Holm, Matilda / Andersson, Emma / Osterlund, Emerik / Ovissi, Ali / Soveri, Leena-Maija / Anttonen, Anna-Kaisa / Kytölä, Soili / Aittomäki, Kristiina / Osterlund, Pia / Ristimäki, Ari

    PloS one

    2020  Volume 15, Issue 11, Page(s) e0239819

    Abstract: Circulating tumor DNA (ctDNA) is released from cancer cells and oncogenic mutations in ctDNA can be measured from plasma samples. Droplet digital PCR (ddPCR) is a sensitive and specific method for the detection of mutations in ctDNA. We analyzed serial ... ...

    Abstract Circulating tumor DNA (ctDNA) is released from cancer cells and oncogenic mutations in ctDNA can be measured from plasma samples. Droplet digital PCR (ddPCR) is a sensitive and specific method for the detection of mutations in ctDNA. We analyzed serial plasma samples (n = 80) from ten metastatic colorectal cancer (mCRC) patients with a known KRAS mutation in their primary tumor. The patients were undergoing oncological treatment with bevacizumab in combination with alternating capecitabine and oxaliplatin or irinotecan. Baseline ddPCR KRAS mutation allele frequency (MAF) values ranged from 0% to 63%. The first radiologic response evaluation criteria in solid tumors (RECIST) evaluation was performed 45-63 days after the initiation of treatment, and by this time three patients had an undetectable level of KRAS mutation, one had a MAF value of 0.5%, and one had a MAF value of 3% that had been reduced by 95% from the baseline value. In three of these patients the RECIST assessment was stable disease and in two partial response. In seven patients, ddPCR MAF values increased before radiological disease progression or death, while one patient remained disease-free with an undetectable KRAS mutation level. Next, we analyzed all available plasma samples with the Idylla ctKRAS system (n = 60), and found that the overall degree of agreement between ddPCR and Idylla was almost perfect (kappa value = 0.860). We used next-generation sequencing (NGS) to detect treatment-induced mutations in the last serial plasma sample of each patient, but were unable to find any new mutations when compared to the primary tumor. This study shows that ddPCR and Idylla are equally efficient for the detection of KRAS mutations in the liquid biopsies from mCRC patients and that ctDNA may indicate the disappearance of treatment responsive KRAS positive mCRC clones and serve as an early sign of disease progression.
    MeSH term(s) Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/therapeutic use ; Biomarkers, Tumor/genetics ; Capecitabine/therapeutic use ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/genetics ; DNA Mutational Analysis/methods ; Female ; Gene Frequency ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Irinotecan/therapeutic use ; Liquid Biopsy/methods ; Male ; Middle Aged ; Oxaliplatin/therapeutic use ; Polymerase Chain Reaction/methods ; Proto-Oncogene Proteins p21(ras)/genetics
    Chemical Substances Biomarkers, Tumor ; Circulating Tumor DNA ; KRAS protein, human ; Oxaliplatin (04ZR38536J) ; Bevacizumab (2S9ZZM9Q9V) ; Capecitabine (6804DJ8Z9U) ; Irinotecan (7673326042) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2020-11-25
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0239819
    Database MEDical Literature Analysis and Retrieval System OnLINE

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