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Article ; Online: Expression profiles of small non-coding RNAs in breast cancer tumors characterize clinicopathological features and show prognostic and predictive potential.

Kärkkäinen, Emmi / Heikkinen, Sami / Tengström, Maria / Kosma, Veli-Matti / Mannermaa, Arto / Hartikainen, Jaana M

2022 Volume 12, Issue 1, Page(s) 22614

Abstract: Precision medicine approaches are required for more effective therapies for cancer. As small non-coding RNAs (sncRNAs) have recently been suggested as intriguing candidates for cancer biomarkers and have shown potential also as novel therapeutic targets, ...

Abstract	Precision medicine approaches are required for more effective therapies for cancer. As small non-coding RNAs (sncRNAs) have recently been suggested as intriguing candidates for cancer biomarkers and have shown potential also as novel therapeutic targets, we aimed at profiling the non-miRNA sncRNAs in a large sample set to evaluate their role in invasive breast cancer (BC). We used small RNA sequencing and 195 fresh-frozen invasive BC and 22 benign breast tissue samples to identify significant associations of small nucleolar RNAs, small nuclear RNAs, and miscellaneous RNAs with the clinicopathological features and patient outcome of BC. Ninety-six and five sncRNAs significantly distinguished (Padj < 0.01) invasive local BC from benign breast tissue and metastasized BC from invasive local BC, respectively. Furthermore, 69 sncRNAs significantly associated (Padj < 0.01) with the tumor grade, hormone receptor status, subtype, and/or tumor histology. Additionally, 42 sncRNAs were observed as candidates for prognostic markers and 29 for predictive markers for radiotherapy and/or tamoxifen response (P < 0.05). We discovered the clinical relevance of sncRNAs from each studied RNA type. By introducing new sncRNA biomarker candidates for invasive BC and validating the potential of previously described ones, we have guided the way for further research that is warranted for providing novel insights into BC biology.
MeSH term(s)	Humans ; Animals ; Female ; RNA, Small Untranslated/genetics ; RNA, Small Untranslated/metabolism ; Breast Neoplasms/genetics ; Prognosis ; Sequence Analysis, RNA ; Mammary Neoplasms, Animal
Chemical Substances	RNA, Small Untranslated
Language	English
Publishing date	2022-12-30
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/s41598-022-26954-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: High Cell-Free DNA Integrity Is Associated with Poor Breast Cancer Survival.

Lamminaho, Maria / Kujala, Jouni / Peltonen, Hanna / Tengström, Maria / Kosma, Veli-Matti / Mannermaa, Arto

Cancers

2021 Volume 13, Issue 18

Abstract: Background: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is ... ...

Abstract	Background: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. Here, we provide further evidence to support the use of cfDI as a potential biomarker. Methods: We selected 204 Eastern Finnish BC cases with non-metastatic disease and isolated cfDNA from the serum collected at the time of diagnosis before any treatment was given. The cfDConc and cfDI were measured with a fluorometer and electrophoresis and analyzed with 25 years of survival data. Results: High cfDConc was not an independent prognostic factor in our analyses while high cfDI was found to be an independent prognostic factor for poor OS ( Conclusions: Our results show high cfDI is an independent prognostic factor for poor OS and BCSS and improves the predictive performance of logistic regression models, thus supporting its prognostic potential.
Language	English
Publishing date	2021-09-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13184679
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Article ; Online: The debatable presence of PIWI-interacting RNAs in invasive breast cancer.

Kärkkäinen, Emmi / Heikkinen, Sami / Tengström, Maria / Kosma, Veli-Matti / Mannermaa, Arto / Hartikainen, Jaana M

Cancer medicine

2021 Volume 10, Issue 11, Page(s) 3593–3603

Abstract: Numerous factors influence breast cancer (BC) prognosis, thus complicating the prediction of outcome. By identifying biomarkers that would distinguish the cases with poorer response to therapy already at the time of diagnosis, the rate of survival could ... ...

Abstract	Numerous factors influence breast cancer (BC) prognosis, thus complicating the prediction of outcome. By identifying biomarkers that would distinguish the cases with poorer response to therapy already at the time of diagnosis, the rate of survival could be improved. Lately, Piwi-interacting RNAs (piRNAs) have been introduced as potential cancer biomarkers, however, due to the recently raised challenges in piRNA annotations, further evaluation of piRNAs' involvement in cancer is required. We performed small RNA sequencing in 227 fresh-frozen breast tissue samples from the Eastern Finnish Kuopio Breast Cancer Project material to study the presence of piRNAs in BC and their associations with the clinicopathological features and outcome of BC patients. We observed the presence of three small RNAs annotated as piRNA database entries (DQ596932, DQ570994, and DQ571955) in our samples. The actual species of these RNAs however remain uncertain. All three small RNAs were upregulated in grade III tumors and DQ596932 additionally in estrogen receptor negative tumors. Furthermore, patients with estrogen receptor positive BC and higher DQ571955 had shorter relapse-free survival and poorer BC-specific survival, thus indicating DQ571955 as a candidate predictive marker for radiotherapy response in estrogen receptor positive BC. DQ596932 showed possible prognostic value in BC, whereas DQ570994 was identified as a candidate predictive marker for tamoxifen and chemotherapy response. These three small RNAs appear as candidate biomarkers for BC, which could after further investigation provide novel approaches for the treatment of therapy resistant BC. Overall, our results indicate that the prevalence of piRNAs in cancer is most likely not as comprehensive as has been previously thought.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Breast/chemistry ; Breast Neoplasms/chemistry ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Disease-Free Survival ; Female ; Humans ; Neoplasm Grading ; Prognosis ; RNA, Small Interfering/analysis ; Radiotherapy ; Receptors, Estrogen/analysis ; Sequence Analysis, RNA ; Tamoxifen/therapeutic use ; Treatment Outcome ; Up-Regulation
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor ; RNA, Small Interfering ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2021-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.3915
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Article: Circulating Cell-Free DNA Reflects the Clonal Evolution of Breast Cancer Tumors.

Kujala, Jouni / Hartikainen, Jaana M / Tengström, Maria / Sironen, Reijo / Auvinen, Päivi / Kosma, Veli-Matti / Mannermaa, Arto

Cancers

2022 Volume 14, Issue 5

Abstract: Liquid biopsy of cell-free DNA (cfDNA) is proposed as a potential method for the early detection of breast cancer (BC) metastases and following the clonal evolution of BC. Though the use of liquid biopsy is a widely discussed topic in the field, only a ... ...

Abstract	Liquid biopsy of cell-free DNA (cfDNA) is proposed as a potential method for the early detection of breast cancer (BC) metastases and following the clonal evolution of BC. Though the use of liquid biopsy is a widely discussed topic in the field, only a few studies have demonstrated such usage so far. We sequenced the DNA of matched primary tumor and metastatic sites together with the matched cfDNA samples from 18 Eastern Finnish BC patients and investigated how well cfDNA reflected the clonal evolution of BC interpreted from tumor DNA. On average, liquid biopsy detected 56.2 ± 7.2% of the somatic variants that were present either in the matched primary tumor or metastatic sites. Despite the high discordance observed between matched samples, liquid biopsy was found to reflect the clonal evolution of BC and identify novel driver variants and therapeutic targets absent from the tumor DNA. Tumor-specific somatic variants were detected in cfDNA at the time of diagnosis and 8.4 ± 2.4 months prior to detection of locoregional recurrence or distant metastases. Our results demonstrate that the sequencing of cfDNA may be used for the early detection of locoregional and distant BC metastases. Observed discordance between tumor DNA sequencing and liquid biopsy supports the parallel sequencing of cfDNA and tumor DNA to yield the most comprehensive overview for the genetic landscape of BC.
Language	English
Publishing date	2022-03-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14051332
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Article ; Online: High mutation burden of circulating cell-free DNA in early-stage breast cancer patients is associated with a poor relapse-free survival.

Kujala, Jouni / Hartikainen, Jaana M / Tengström, Maria / Sironen, Reijo / Kosma, Veli-Matti / Mannermaa, Arto

Cancer medicine

2020 Volume 9, Issue 16, Page(s) 5922–5931

Abstract: Background: High tumor mutation burden is shown to be associated with a poor clinical outcome. As the tumor-derived fraction of circulating cell-free DNA (cfDNA) is shown to reflect the genetic spectrum of the tumor, we examined whether the mutation ... ...

Abstract	Background: High tumor mutation burden is shown to be associated with a poor clinical outcome. As the tumor-derived fraction of circulating cell-free DNA (cfDNA) is shown to reflect the genetic spectrum of the tumor, we examined whether the mutation burden of cfDNA could be used to predict the clinical outcomes of early-stage breast cancer (BC) patients. Methods: We selected a set of 79 Finnish early-stage BC cases with a good prognosis based on traditional prognostic parameters but some of which still developed relapsed disease during follow-up. cfDNA was isolated from the serum collected at the time of diagnosis, sequenced, and compared to matched primary tumors, clinical parameters, and survival data. Results: High cfDNA mutation burden was associated with the poor relapse-free survival (RFS) (P = .016, HR = 2.23, 95% Cl 1.16-4.27) when patients were divided into high and low mutation burden according to the median number of somatic variants. A high discordance was observed between the matched tumor and cfDNA samples, thus highlighting the challenges related to the liquid biopsy of early-stage cancer cases. Despite the low number of detected tumor-specific variants, the presence of tumor-specific somatic variants in the cfDNA was associated with the poor RFS (P = .009, HR = 2.31, 95% Cl 1.23-4.31). Conclusions: Our results confirm previously observed challenges about the accuracy of liquid biopsy-based genotyping of early-stage cancers and support the parallel sequencing of tumor and cfDNA while also demonstrating how the presence of tumor-specific somatic variants and the high mutation burden in the cfDNA are both associated with the poor RFS, thus indicating the prognostic potential of liquid biopsy in the context of early-stage cancers.
MeSH term(s)	Adult ; Aged ; Breast Neoplasms/blood ; Breast Neoplasms/genetics ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Cell-Free Nucleic Acids/blood ; Cell-Free Nucleic Acids/genetics ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; Disease-Free Survival ; Female ; Finland ; Genotype ; Humans ; Liquid Biopsy ; Middle Aged ; Mutation ; Prognosis ; Sequence Analysis, DNA
Chemical Substances	Cell-Free Nucleic Acids ; Circulating Tumor DNA
Language	English
Publishing date	2020-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2045-7634
ISSN (online)	2045-7634
DOI	10.1002/cam4.3258
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Article ; Online: Predicting breast cancer risk using interacting genetic and demographic factors and machine learning.

Behravan, Hamid / Hartikainen, Jaana M / Tengström, Maria / Kosma, Veli-Matti / Mannermaa, Arto

Scientific reports

2020 Volume 10, Issue 1, Page(s) 11044

Abstract: Breast cancer (BC) is a multifactorial disease and the most common cancer in women worldwide. We describe a machine learning approach to identify a combination of interacting genetic variants (SNPs) and demographic risk factors for BC, especially factors ...

Abstract	Breast cancer (BC) is a multifactorial disease and the most common cancer in women worldwide. We describe a machine learning approach to identify a combination of interacting genetic variants (SNPs) and demographic risk factors for BC, especially factors related to both familial history (Group 1) and oestrogen metabolism (Group 2), for predicting BC risk. This approach identifies the best combinations of interacting genetic and demographic risk factors that yield the highest BC risk prediction accuracy. In tests on the Kuopio Breast Cancer Project (KBCP) dataset, our approach achieves a mean average precision (mAP) of 77.78 in predicting BC risk by using interacting genetic and Group 1 features, which is better than the mAPs of 74.19 and 73.65 achieved using only Group 1 features and interacting SNPs, respectively. Similarly, using interacting genetic and Group 2 features yields a mAP of 78.00, which outperforms the system based on only Group 2 features, which has a mAP of 72.57. Furthermore, the gene interaction maps built from genes associated with SNPs that interact with demographic risk factors indicate important BC-related biological entities, such as angiogenesis, apoptosis and oestrogen-related networks. The results also show that demographic risk factors are individually more important than genetic variants in predicting BC risk.
MeSH term(s)	Algorithms ; Breast Neoplasms/etiology ; Breast Neoplasms/genetics ; Databases, Factual ; Databases, Genetic ; Demography ; Epistasis, Genetic ; Female ; Genetic Predisposition to Disease ; Humans ; Machine Learning ; Polymorphism, Single Nucleotide ; Risk Factors
Language	English
Publishing date	2020-07-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-66907-9
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Article ; Online: Machine learning identifies interacting genetic variants contributing to breast cancer risk: A case study in Finnish cases and controls.

Behravan, Hamid / Hartikainen, Jaana M / Tengström, Maria / Pylkäs, Katri / Winqvist, Robert / Kosma, Veli-Matti / Mannermaa, Arto

Scientific reports

2018 Volume 8, Issue 1, Page(s) 13149

Abstract: We propose an effective machine learning approach to identify group of interacting single nucleotide polymorphisms (SNPs), which contribute most to the breast cancer (BC) risk by assuming dependencies among BCAC iCOGS SNPs. We adopt a gradient tree ... ...

Abstract	We propose an effective machine learning approach to identify group of interacting single nucleotide polymorphisms (SNPs), which contribute most to the breast cancer (BC) risk by assuming dependencies among BCAC iCOGS SNPs. We adopt a gradient tree boosting method followed by an adaptive iterative SNP search to capture complex non-linear SNP-SNP interactions and consequently, obtain group of interacting SNPs with high BC risk-predictive potential. We also propose a support vector machine formed by the identified SNPs to classify BC cases and controls. Our approach achieves mean average precision (mAP) of 72.66, 67.24 and 69.25 in discriminating BC cases and controls in KBCP, OBCS and merged KBCP-OBCS sample sets, respectively. These results are better than the mAP of 70.08, 63.61 and 66.41 obtained by using a polygenic risk score model derived from 51 known BC-associated SNPs, respectively, in KBCP, OBCS and merged KBCP-OBCS sample sets. BC subtype analysis further reveals that the 200 identified KBCP SNPs from the proposed method performs favorably in classifying estrogen receptor positive (ER+) and negative (ER-) BC cases both in KBCP and OBCS data. Further, a biological analysis of the identified SNPs reveals genes related to important BC-related mechanisms, estrogen metabolism and apoptosis.
MeSH term(s)	Base Sequence ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Case-Control Studies ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Female ; Finland ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; Genome, Human ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; Prognosis ; Protein Interaction Mapping ; Risk ; Support Vector Machine ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	ESR1 protein, human ; Estrogen Receptor alpha ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27)
Language	English
Publishing date	2018-09-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-31573-5
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Article ; Online: SULT1A1 rs9282861 polymorphism-a potential modifier of efficacy of the systemic adjuvant therapy in breast cancer?

Tengström Maria / Mannermaa Arto / Kosma Veli-Matti / Hirvonen Ari / Kataja Vesa

BMC Cancer, Vol 12, Iss 1, p

2012 Volume 257

Abstract: Abstract Background Sulfotransferase 1A1 (SULT1A1) participates in the elimination of 4-hydroxy-tamoxifen (4-OH-TAM), which is one of the major active metabolites of tamoxifen (TAM). Homozygous SULT1A1 variant allele genotype has been associated with ... ...

Abstract	Abstract Background Sulfotransferase 1A1 (SULT1A1) participates in the elimination of 4-hydroxy-tamoxifen (4-OH-TAM), which is one of the major active metabolites of tamoxifen (TAM). Homozygous SULT1A1 variant allele genotype has been associated with lower catalytic activity and thermostability of the enzyme. Previous clinical studies suggest that the SULT1A1 rs9282861 polymorphism may influence the survival of breast cancer patients treated with TAM in the adjuvant setting. We investigated the effect of rs9282861 genotypes on the survival of Finnish breast cancer patients treated with adjuvant chemotherapy or TAM. Methods The rs9282861 genotypes of 412 Finnish breast cancer patients with early breast cancer were identified by using PCR-RFLP method. Seventy six patients were treated with adjuvant cyclophosphamide based chemotherapy only, 65 patients received adjuvant TAM, and four patients were treated with both adjuvant chemotherapy and TAM. Overall long-term survival (OS), breast cancer specific survival (BCSS), and relapse-free survival (RFS) by rs9282861 genotypes were evaluated by the Kaplan-Meier method and Cox regression analysis. Results The multivariate analysis of 145 patients receiving either adjuvant TAM or chemotherapy showed a statistically significantly improved OS in patients with the rs9282861 homozygous variant AA genotype (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.29-0.88, P = 0.015). In the separate analyses of patients receiving only chemotherapy or adjuvant TAM, there were no statistically significant differences in survival. Conclusions In this prospective study, we observed a previously unreported association between the SULT1A1 rs9282861 genotype and OS of breast cancer patients treated with adjuvant chemotherapy or TAM. This novel finding suggests that the rs9282861 polymorphism modifies the long-term clinical outcome of patients receiving adjuvant TAM or chemotherapy.
Keywords	Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610 ; 616
Language	English
Publishing date	2012-06-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
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Article ; Online: XRCC1 rs25487 polymorphism predicts the survival of patients after postoperative radiotherapy and adjuvant chemotherapy for breast cancer.

Tengström, Maria / Mannermaa, Arto / Kosma, Veli-Matti / Hirvonen, Ari / Kataja, Vesa

Anticancer research

2014 Volume 34, Issue 6, Page(s) 3031–3037

Abstract: Background: Single nucleotide polymorphisms (SNPs) in a DNA-repair gene, X-Ray repair cross complementing group 1 (XRCC1), have been associated with the survival of patients with breast cancer. We investigated the predictive value of XRCC1 SNP (rs25487) ...

Abstract	Background: Single nucleotide polymorphisms (SNPs) in a DNA-repair gene, X-Ray repair cross complementing group 1 (XRCC1), have been associated with the survival of patients with breast cancer. We investigated the predictive value of XRCC1 SNP (rs25487) in patients with early breast cancer. Patients and methods: The XRCC1 rs25487 genotypes of 411 Finnish patients with breast cancer were analyzed by a polymerase chain reaction-restriction fragment length polymorphism-based method. Survival was assessed by Kaplan-Meier method and Cox regression analysis according to the XRCC1 genotypes in specified adjuvant treatment groups. Results: The rs25487 variant AA genotype was associated with worse breast cancer-specific and overall survival in 238 patients receiving postoperative radiotherapy (p=0.031 and p=0.030, respectively). The AA genotype predicted worse breast cancer-specific survival among 75 patients treated with adjuvant chemotherapy (p=0.047). Conclusion: The XRCC1 rs25487 genotype may predict the outcome of postoperative radiotherapy and adjuvant chemotherapy in breast cancer.
MeSH term(s)	Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics ; Breast Neoplasms/mortality ; Breast Neoplasms/therapy ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Ductal, Breast/mortality ; Carcinoma, Ductal, Breast/therapy ; Carcinoma, Lobular/genetics ; Carcinoma, Lobular/mortality ; Carcinoma, Lobular/therapy ; Case-Control Studies ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; DNA-Binding Proteins/genetics ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/therapy ; Neoplasm Staging ; Polymerase Chain Reaction ; Polymorphism, Genetic/genetics ; Polymorphism, Restriction Fragment Length ; Postoperative Period ; Prognosis ; Prospective Studies ; Radiotherapy Dosage ; Survival Rate ; X-ray Repair Cross Complementing Protein 1
Chemical Substances	Biomarkers, Tumor ; DNA-Binding Proteins ; X-ray Repair Cross Complementing Protein 1 ; XRCC1 protein, human
Language	English
Publishing date	2014-06
Publishing country	Greece
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article ; Online: MnSOD rs4880 and XPD rs13181 polymorphisms predict the survival of breast cancer patients treated with adjuvant tamoxifen.

Tengström, Maria / Mannermaa, Arto / Kosma, Veli-Matti / Soini, Ylermi / Hirvonen, Ari / Kataja, Vesa

Acta oncologica (Stockholm, Sweden)

2014 Volume 53, Issue 6, Page(s) 769–775

Abstract: Unlabelled: The enzyme manganese superoxide dismutase (MnSOD) defends against oxidative stress caused by reactive oxygen species (ROS), whereas Xeroderma pigmentosum group D (XPD) protein is involved in DNA repair. Polymorphisms in these genes have ... ...

Abstract	Unlabelled: The enzyme manganese superoxide dismutase (MnSOD) defends against oxidative stress caused by reactive oxygen species (ROS), whereas Xeroderma pigmentosum group D (XPD) protein is involved in DNA repair. Polymorphisms in these genes have previously been associated with the outcome of breast cancer. Material and methods: Two gene polymorphisms, the MnSOD Val16Ala (rs4880A>G) and the XPD Lys751Gln (rs13181A>C), were analyzed in a cohort of 396 Finnish breast cancer patients by using PCR-RFLP-based methods in a prospective case-control study. The overall survival (OS), breast cancer-specific survival (BCSS), and relapse-free survival (RFS), assessed by using Kaplan-Meier survival analysis and multivariate Cox regression analysis, were evaluated according to the adjuvant treatments and the rs4880 and rs13181 genotypes. Results: In the combined analysis of rs4880 and rs13181 genotypes for patients treated with adjuvant tamoxifen (TAM) an increasing number of low-risk genotypes (rs4880 AA, rs4880 AG, or rs13181 AA) was significantly associated with better RFS, BCSS, and OS (n=64). In addition, there was improved BCSS and RFS among TAM-treated patients carrying the wild-type rs4880 A allele as compared with the other genotypes (n=64). The wild-type rs13181 AA genotype was similarly associated with better RFS and BCSS in the TAM-treated population (n=65). Conclusion: This is the first study to show that the MnSOD rs4880 and XPD rs13181 polymorphisms may influence the outcome of breast cancer patients receiving adjuvant TAM monotherapy. Patients carrying the rs4880 A allele or rs13181 AA genotype may have a reduced ability to scavenge ROS and repair the DNA damage generated by TAM treatment.
MeSH term(s)	Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/mortality ; Carcinoma/drug therapy ; Carcinoma/genetics ; Carcinoma/mortality ; Case-Control Studies ; Chemotherapy, Adjuvant ; Cohort Studies ; Disease-Free Survival ; Female ; Genotype ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Polymorphism, Single Nucleotide ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Superoxide Dismutase/genetics ; Tamoxifen/therapeutic use ; Xeroderma Pigmentosum Group D Protein/genetics
Chemical Substances	Antineoplastic Agents, Hormonal ; Tamoxifen (094ZI81Y45) ; Superoxide Dismutase (EC 1.15.1.1) ; Xeroderma Pigmentosum Group D Protein (EC 3.6.4.12) ; ERCC2 protein, human (EC 5.99.-)
Language	English
Publishing date	2014-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
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	10.3109/0284186X.2014.892210
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