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- Bevier, Melanie, et al.
(author)
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Does the time interval between first and last birth influence the risk of endometrial and ovarian cancer?
- 2011
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In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 47:4, s. 586-591
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Journal article (peer-reviewed)abstract
- Background: Age at first and last birth and the number of children are known to influence the risk of endometrial and ovarian cancers. However, it remains unknown whether the difference in years between first and last childbirth plays a role. The Swedish Family-Cancer Database allowed us to carry out the largest study ever on reproductive factors in these cancers. Material and methods: We selected over 5.7 million women from the database. We estimated the effect of number of children, age at birth and difference between age at first and last birth by Poisson regression adjusted for age, period, region and socioeconomic status. Results: The risk for endometrial cancer is negatively associated with increasing number of children and increasing age at first as well as age at last birth. Weaker associations are found for ovarian cancer. Age at last birth is the factor that shows highest influence. A large difference in first and last childbirth shows a protective effect on the risk of endometrial cancer. Conclusion: Our findings suggest that the risk of endometrial cancer is significantly decreased for women having at least a difference of 10 years between their first and last birth. Ovarian cancer does not seem to be influenced by the time interval between first and last birth. (c) 2010 Elsevier Ltd. All rights reserved.
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| 2. |
- Bevier, Melanie, et al.
(author)
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Influence of family size and birth order on risk of cancer: a population-based study
- 2011
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
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Journal article (peer-reviewed)abstract
- Background: Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family Cancer Database to further analyze these effects. Methods: We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Results: Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Conclusion: Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer.
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| 3. |
- Shi, Hong, et al.
(author)
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Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome
- 2011
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In: Breast Cancer Research and Treatment. - New York : Springer-Verlag New York. - 0167-6806 .- 1573-7217. ; 130:3, s. 905-916
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Journal article (peer-reviewed)abstract
- The 20q13 region is frequently amplified/overexpressed in breast tumours. However, the nature of this amplification/overexpression is unknown. Here, we investigated genetic variation in five 20q13 amplicon genes (MYBL2, AURKA, ZNF217, STK4 and PTPN1) and its impact on breast cancer (BC) susceptibility and clinical outcome. As a novel finding, four polymorphisms in STK4 (rs6017452, rs7271519) and AURKA (rs2273535, rs8173) associated with steroid hormone receptor status both in a Swedish population-based cohort of 783 BC cases and in a Polish familial/early onset cohort of 506 BC cases. In the joint analysis, the minor allele carriers of rs6017452 had more often hormone receptor positive tumours (OR 0.57, 95% CI 0.40-0.81), while homozygotes for the minor allele of rs7271519, rs2273535 and rs8173 had more often hormone receptor negative tumours (2.26, 1.30-3.39; 2.39, 1.14-5.01; 2.39, 1.19-4.80, respectively) than homozygotes for the common allele. BC-specific survival analysis of AURKA suggested that the Swedish carriers of the minor allele of rs16979877, rs2273535 and rs8173 might have a worse survival compared with the major homozygotes. The survival probabilities associated with the AURKA genotypes depended on the tumour phenotype. In the Swedish case-control study, associations with BC susceptibility were observed in a dominant model for three MYBL2 promoter polymorphisms (rs619289, P = 0.02; rs826943, P = 0.03 and rs826944, P = 0.02), two AURKA promoter polymorphisms (rs6064389, P = 0.04 and rs16979877, P = 0.02) and one 3'UTR polymorphism in ZNF217 (rs1056948, P = 0.01). In conclusion, our data confirmed the impact of the previously identified susceptibility locus and provided preliminary evidence for novel susceptibility variants in BC. We provided evidence for the first time that genetic variants at 20q13 may affect hormone receptor status in breast tumours and influence tumour aggressiveness and survival of the patients. Future studies are needed to confirm the prognostic value of our findings in the clinic.
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| 4. |
- Varadi, Verena, et al.
(author)
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Genetic variation in genes encoding for polymerase zeta subunits associates with breast cancer risk, tumour characteristics and survival
- 2011
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 129:1, s. 235-245
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Journal article (peer-reviewed)abstract
- Chromosomal instability is a known hallmark of many cancers. DNA polymerases represent a group of enzymes that are involved in the mechanism of chromosomal instability as they have a central function in DNA metabolism. We hypothesized that genetic variation in the polymerase genes may affect gene expression or protein configuration and by that cancer risk and clinical outcome. We selected four genes encoding for the catalytic subunits of the polymerases beta, delta, theta and zeta (POLB, POLD1, POLQ and REV3L, respectively) and two associated proteins (MAD2L2 and REV1) because of their previously reported association with chromosomal instability and/or tumorigenesis. We selected potentially functional and most informative tagging single nucleotide polymorphisms (SNPs) for genotyping in a population-based series of 783 Swedish breast cancer (BC) cases and 1562 controls. SNPs that showed a significant association in the Swedish population were additionally genotyped in a Polish population consisting of 506 familial/early onset BC cases and 568 controls. SNPs in all three polymerase zeta subunit genes associated either with BC risk or prognosis. Two SNPs in REV3L and one SNP in MAD2L2 associated with BC risk: rs462779 (multiplicative model: OR 0.79, 95% CI 0.68-0.92), rs3204953 (dominant model: OR 1.28, 95% CI 1.05-1.56) and rs2233004 (recessive model: OR 0.49, 95% CI 0.28-0.86). Homozygous carriers of the minor allele C of the third SNP in REV3L, rs11153292, had significantly worse survival compared to the TT genotype carriers (HR 2.93, 95% CI 1.34-6.44). Minor allele carriers of two REV1 SNPs (rs6761391 and rs3792142) had significantly more often large tumours and tumours with high histological grade and stage. No association was observed for SNPs in POLB, POLQ and POLD1. Altogether, our data suggest a significant role of genetic variation in the polymerase zeta subunit genes regarding the development and progression of BC.
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