| 1. |
- Ellberg, Carolina, et al.
(författare)
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Impact of a paternal origin of germline BRCA1/2 mutations on the age at breast and ovarian cancer diagnosis in a Southern Swedish cohort.
- 2015
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 54:1, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin. © 2014 Wiley Periodicals, Inc.
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| 2. |
- Henningson, Maria, et al.
(författare)
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Absence of the common IGF1 19 CA-repeat allele is more common among BRCA1 mutation carriers than among non-carriers from BRCA1 families.
- 2007
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:4, s. 445-452
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 mutations predispose to early-onset breast cancer. We previously reported an association between absence of the common IGF1 19 CA-repeat allele (IGF1-19/-19) and being a BRCA1 mutation carrier in young women from breast cancer high-risk families. Others have reported a four-fold risk of premenopausal breast cancer in women with a family history and the IGF1-19/-19 genotype. The aim of this study was to investigate whether the IGF1-19/-19 genotype was associated with being a BRCA1 mutation carrier among women from BRCA1 families. DNA was available from 268 women with known BRCA1 status from the South Swedish Health Care Region. IGF1 genotyping was successfully performed with fragment analysis in 211 women from 96 families. The IGF1-19/-19 genotype was significantly more common among BRCA1 mutation carriers (14.2%) than among non-carriers (4.8%), OR 3.3 (95%CI 1.11-9.78, P = 0.03) adjusted for family clustering. We confirmed our previous finding of an association between the IGF1-19/-19 genotype and BRCA1 mutation status. Since the IGF1-19/-19 genotype in combination with OC use or multiparity confers an increased risk for early onset breast cancer in high-risk women and in women from the general population, future studies are needed to elucidate the importance of the IGF1-19/-19 genotype concerning the variability in breast cancer risk among BRCA1 mutation carriers.
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| 3. |
- Henningson, Maria, et al.
(författare)
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CYP17 genotype is associated with short menstrual cycles, early oral contraceptive use and BRCA mutation status in young healthy women
- 2007
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 13:4, s. 231-236
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Tidskriftsartikel (refereegranskat)abstract
- The CYP17 gene is involved in steroid hormone metabolism and has been proposed as a low penetrance gene for breast cancer. We aimed to investigate the associations between the CYP17 genotype and breast cancer risk factors, such as age at menarche, menstrual cycle length, oral contraceptive (OC) use, and BRCA mutation status among 258 healthy young women, aged <= 40, from 158 breast cancer high-risk families. Questionnaires including questions on reproductive factors and OC use were completed and blood samples were obtained from all women. CYP17 (rs743572) was genotyped with sequencing in 254 women. The main findings were that short menstrual cycles (< 27 days) were significantly more common with increasing number of variant A2 alleles (8%, 17% and 32%; P-trend = 0.002, adjusted for family clustering). Each A2 allele was associated with a 7 months earlier OC start (17.8, 17.0, and 16.6 years; P-trend = 0.014, adjusted for age at menarche, ever-smoking and family clustering). Homozygosity for the A2 allele was more common among known non-carriers from BRCA1/2 families compared with other high-risk women OR 2.92 (95% CI 1.49-5.73; P = 0.002, adjusted for family clustering). We found no association between CYP17 genotype and age at menarche. In conclusion, this study suggests that short menstrual cycles, age at first OC use and BRCA mutation status may need to be considered in studies exploring the relationships between CYP17 and risk factors for early onset breast cancer.
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| 4. |
- Hietala, M, et al.
(författare)
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Testosterone levels in relation to oral contraceptive use and the androgen receptor CAG and GGC length polymorphisms in healthy young women
- 2007
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 22:1, s. 83-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The combined effect from the androgen receptor (AR) CAG and GGC length polymorphisms on testosterone levels has not been studied in young women. METHODS: Testosterone levels were measured in blood drawn on both menstrual cycle days 5-10 and 18-23 in 258 healthy women, aged <= 40 years, from high-risk breast cancer families. CAG and GGC length polymorphisms were analysed by PCR and fragment analyses. All women completed a questionnaire including information on oral contraceptive (OC) use and reproductive factors. RESULTS: OC users had lower median testosterone levels than non-users during cycle days 5-10 and 18-23 (P <= 0.005 for both). The BRCA mutation status was associated neither with testosterone levels nor with CAG or GGC length polymorphism. The CAG length polymorphism was not associated with testosterone levels. The cumulative number of long GGC alleles (>= 17 repeats) was significantly associated with lower testosterone levels in OC users during cycle days 5-10 (P-trend =0.014), but not during cycle days 18-23 or in non-users. The interaction between the GGC length polymorphism and OC status was highly significant during cycle days 5-10 (P = 0.002) and near-significant during days 18-23 (P = 0.07). Incident breast cancer was more common in women with two short GGC alleles (log-rank P = 0.003). CONCLUSION: The GGC repeat length was the only significant genetic factor modifying the testosterone levels in current OC users from high-risk families. Homozygosity for the short GGC allele may be linked to the increased risk of early-onset breast cancer after OC exposure in high-risk women.
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| 5. |
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| 6. |
- Jernström, Helena, et al.
(författare)
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Do BRCA1 mutations affect the ability to breast feed? Significantly shorter length of breast feeding among BRCA1 mutation carriers compared with their unaffected relatives.
- 1998
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Ingår i: Breast. - 1532-3080. ; 7:6, s. 320-324
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Tidskriftsartikel (refereegranskat)abstract
- The difference in length of breast feeding between women with a BRCA 1 mutation and their unaffected relatives was investigated. Fifty women belonging to a family with a known BRCA1 mutation had themselves undergone testing and each had given birth to at least one child. Women with BRCA1 mutation breast-fed their first infant for a significantly shorter period (P = 0.048) and the second and third infants for a non-significantly shorter time than their unaffected relatives. Computing a mean breast-feeding time per child based on the first three infants and also taking birth year of the mother and smoking into account, having a BRCA1 mutation was associated with a significantly shorter time of breast-feeding (P = 0.034), and so was smoking (P = 0.001), but birth year of the woman did not significantly influence length of breast-feeding. Seventy-five per cent of the assessable women with a BRCA1 mutation stopped breast-feeding owing to little or no milk production compared with 36% of the non-carriers OR = 5.3 (CI 95% 1.1–22.1) and (P = 0.02). Our finding may reflect a disturbed differentiation of the breast tissue in women with BRCA1 mutations.
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| 7. |
- Jernström, Helena, et al.
(författare)
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High follicular phase luteinizing hormone levels in young healthy BRCA1 mutation carriers: Implications for breast and ovarian cancer risk.
- 2005
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 86:1-2, s. 320-327
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 mutation carriers have up to 80% life-time risk of developing breast cancer and 20-40% risk of developing ovarian cancer. High LH levels have been linked to increased risks of both breast and ovarian cancers in some studies and it is unknown whether gonadotropin levels are associated with BRCA1 mutation status. The aim of the study was to explore whether gonadotropin levels were associated with BRCA1 mutation status among healthy <= 40-year-old-women from hereditary breast cancer families. All women completed a questionnaire including information on reproductive factors and OC use. We measured height, weight, breast volumes, and plasma levels of LH, FSH, and estradiol (E2) once during menstrual cycle days 5-10 and once again during cycle days 18-23 in 43 non-carriers from BRCA1 families, 20 BRCA1 mutation carriers, and 101 women from non-BRCA1/2 families. The strongest predictors of high LH levels among BRCA1 mutation carriers and non-carriers during cycle days 5-10 were being a BRCA1 mutation carrier (p = 0.002), lack of current OC use (p = 0.003), and being nulliparous (p = 0.01), adjusted for age and menstrual cycle day when the samples were obtained. This association was seen both in non-OC users and current OC users but was only significant in the former group (p = 0.005). Because of multiple analyses it is possible that our finding is a result of a Type 1 statistical error. After a permutation test the new adjusted p value in non-OC users was 0.05. FSH and E2 were similar in non-carriers, BRCA1 mutation carriers and women from non-BRCA1/2 families. We found significantly elevated LH levels in the follicular phase among young healthy BRCA1 mutation carriers compared with non-carriers from BRCA1 families. This is a small study and confirmatory studies are warranted to establish whether elevated LH levels are part of the BRCA1 phenotype and may be manipulated in order to reduce cancer risks in BRCA1 mutation carriers.
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| 8. |
- Jernström, Helena, et al.
(författare)
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Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing
- 2005
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 41:15, s. 2312-2320
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Tidskriftsartikel (refereegranskat)abstract
- Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged <= 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.
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