| 1. |
- Wagner, Philippe, et al.
(author)
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Increased cancer risks among arthroplasty patients: 30year follow-up of the Swedish Knee Arthroplasty Register.
- 2011
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In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 47:7, s. 1061-1071
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Journal article (peer-reviewed)abstract
- BACKGROUND: An increasing number of young patients are undergoing knee arthroplasties. Thus, the long-term risks of having a knee prosthesis must be evaluated. This study focuses on the potential carcinogenic effects of the prosthesis; it is a long-term follow-up of all patients in Sweden between 1975 and 2006. METHODS: The incidence of cancer in a total population of operated individuals was compared to the overall national cancer incidence in Sweden by means of standardised incidence ratios. Analysis of cancer latency period was performed to identify potential aetiological factors. RESULTS: For male and female patients with rheumatoid arthritis (RA) or osteoarthritis (OA), the overall cancer risks were elevated, ranging from 1.10 (95% confidence interval (CI): 1.03-1.18) for men with OA to 1.26 (1.23-1.29) for men with RA. The greatest increases in risk were observed for the leukaemia subtypes, myelodysplastic syndromes (MDS) and essential thrombocytosis (ET), ranging from 3.31 (1.24-8.83) for ET in men with OA to 7.38 (1.85-29.51) for ET in women with RA. Increases in risk were also observed for breast cancer, prostate cancer and melanoma. The latency analysis revealed elevated risks late in the study period for both solid and haematopoietic cancers. However, only increases in MDS and possibly prostate cancer and melanoma rates appeared to be connected to the operation. CONCLUSION: This study showed that OA and RA arthroplasty patients have a significantly higher risk of cancer than the general population. Elevated risks of MDS and possibly prostate cancer and melanoma indicated a potential connection to exposure to metals in the implant. The observed excessive incidence of ET was likely associated with the inflammatory disease.
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| 2. |
- Wirfält, Elisabet, et al.
(author)
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Food sources of fat and sex hormone receptor status of invasive breast tumors in women of the malmö diet and cancer cohort.
- 2011
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In: Nutrition and Cancer. - : Informa UK Limited. - 1532-7914 .- 0163-5581. ; 63:5, s. 722-733
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Journal article (peer-reviewed)abstract
- We examined associations between food intakes and incident breast cancer, defined by estrogen receptor (ER) and progesterone receptor (PR) status in the Malmö Diet and Cancer cohort (17,000 women aged 45-73 yr). The hazard ratios (HRs) of ER+PR+ (n = 270), ER+PR- (n = 87), and ER-PR- (n = 61) tumors and all cancer (n = 544) were estimated after 10 yr of follow-up. In multivariate analysis of ER+PR+ tumors, a protective linear risk trend, indicating change between adjoining food categories, was seen with yogurt (HR = 0.89, 95% CI = 0.80-0.99), but increased risks with eggs (HR = 1.10, 95% CI = 1.01-1.20) and dried soups/sauces (HR = 1.10, 95% CI = 1.00-1.22). In ER-PR- tumors, vegetable-oil-based margarine (HR = 1.31, 95% CI = 1.09-1.59) and dried soups/sauces (HR = 1.31 95% CI = 1.05-1.64) showed increased risks. Heterogeneity was observed between ER+PR+ and ER-PR- tumors for vegetable-oil-based margarine (P < 0.01). Regular milk showed decreased, and dried soups/sauces increased, risk with all breast cancer. The study suggests that fat-containing food may contribute both to hormonal and nonhormonal mechanisms in breast tumor development and supports observations of positive associations between characteristics of Westernized diets and postmenopausal breast cancer.
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| 3. |
- Barrett, Jennifer H., et al.
(author)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Journal article (peer-reviewed)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 4. |
- Bertolotto, Corine, et al.
(author)
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A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 480:7375, s. 94-98
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Journal article (peer-reviewed)abstract
- So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes(1); risk factors associated with RCC include smoking, obesity and hypertension(2). A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers(3). The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene(4); it also stimulates the transcription of hypoxia inducible factor(5) (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes(6). We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (Psi KXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
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| 5. |
- Carlsson, Anders, et al.
(author)
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Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases.
- 2011
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 108:34, s. 14252-14257
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Journal article (peer-reviewed)abstract
- The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into high- versus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.
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| 6. |
- Sjövall, Katarina, et al.
(author)
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Experiences of living with advanced colorectal cancer from two perspectives - Inside and outside.
- 2011
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In: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889. ; 15, s. 390-397
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate how life situation by persons with advanced colorectal cancer and their partners is affected by living with the disease and its treatment. METHOD: Separate, individual interviews were made with persons with advanced colorectal cancer (n = 12) and their partners (n = 9) about how their daily lives were affected by the disease and its treatment. The verbatim transcripts were analysed using content analysis. RESULTS: Living with the illness of advanced colorectal cancer was experienced to be: being inside or outside the healthcare system, striving for normality and becoming conscious of life's value and vulnerability. Living as a partner was experienced as living in an altered relation and as living in the shadow of the disease. CONCLUSIONS: When one in a partner relation suffers from colorectal cancer, it changes life and life perspective for both partners. Partners need to be invited to and involved in the care. Cancer nursing should focus on supporting the strive for normality in daily life, as the disease and its' treatment may last for a longer period of time. Supporting the partner may benefit the person with cancer as well, to cope along the illness trajectory.
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| 7. |
- Henningson, Maria, et al.
(author)
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IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early-onset breast cancer
- 2011
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In: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 10:2, s. 173-185
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Journal article (peer-reviewed)abstract
- High levels of insulin-like growth factor-1 (IGF-1) have been associated with increased risk of developing several types of cancer including breast cancer. A set of nine haplotype tagging SNPs (htSNPs) in the IGF1 gene were associated with IGF-1 levels and prostate cancer in a Swedish population. We aimed to study the nine htSNPs in three haplotype blocks (block1: rs855211, rs35765, rs2162679; block2: rs1019731, rs7956547, rs5742632; and block3 rs2033178, rs7136446, rs6220) combined into diplotypes, and three additional SNPs (rs5742612, rs35765817, rs35455143) in relation to IGF-1 levels, BRCA status, the IGF1 CA-repeat microsatellite, and breast cancer in a population of 325 Swedish women from breast cancer high-risk families. Questionnaire data and blood samples for IGF-1 and genetic analyses were obtained twice during the menstrual cycle from 269 women aged 40 years or younger. SNP analyses were also performed in 56 BRCA1/2 mutation carriers. Women (n = 14) with any rare variant block1 diplotype had higher odds to be BRCA1 mutation carriers OR 4.1 (95% CI 1.4-12.2), to lack the common IGF1 19 CA-repeat allele OR 33.3 (95% CI 6.6-166.7), and were more likely to develop early-onset breast cancer (Log Rank P < 0.001) than women with common block1 diplotypes. In the subgroup of BRCA1 mutation carriers, block1 rare diplotypes were associated with earlier diagnosis (Log Rank P = 0.031). No association was found between IGF-1 levels and individual SNPs or diplotypes. If confirmed, these rare diplotypes may identify women with particularly high risk for early-onset breast cancer and this group should be included in forthcoming studies.
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| 8. |
- Johansson, Ida, et al.
(author)
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High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer
- 2011
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 129:3, s. 747-760
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Journal article (peer-reviewed)abstract
- Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC subgroup, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male-simple subgroup appears notably different from any genomic subgroup so far defined in FBC.
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| 9. |
- Ellberg, Carolina, et al.
(author)
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Breast cancer patients with lobular cancer more commonly have a father than a mother diagnosed with cancer
- 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: The association between lobular breast cancer and family history is not clear. The aim of the study was to possibly identifying new hereditary patterns predisposing for cancer in the different histopathologic subtypes of breast cancer, with focus on patients with lobular breast cancer and cancer in their first degree relatives. Methods: In 1676 consecutive breast cancer patients detailed family history of cancer was related to histopathologic subtype of breast cancer. Results: Patients with lobular breast cancer were found to be significantly positively associated with having a father diagnosed with cancer, OR 2.17 (95% confidence interval (CI) 1.37-3.46). The finding persisted after excluding breast cancer in the family. Ductal breast cancer was associated with having a mother diagnosed with cancer. There was a significant association between lobular breast cancer and having a father with prostate cancer, OR 2.4 (CI 1.1-5.3). The occurrence of having a father with prostate cancer for lobular breast cancer patients was higher in the younger patient group, OR 2.9 (CI 1.1-7.8), and was still high but lost statistical significance in the older patient group, OR 1.9 (CI 0.5-7.4). The association between lobular breast cancer and a father remained significant after excluding fathers with prostate cancer, OR 1.94 (CI 1.20-3.14). Other commonly occurring tumor types in the father included sarcoma and leukemia. Conclusion: We propose that lobular breast cancer is associated with having a father diagnosed with cancer, most commonly prostate carcinoma. Since the association remained after excluding family history of breast cancer, the association seems independent of classical breast cancer heredity. The association with a father diagnosed with cancer also remained after removing prostate cancer, indicating an independence from prostate cancer as well. The reason for this association is genetically unclear, but could involve sex-specific imprinting.
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| 10. |
- Hietala, Maria, et al.
(author)
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Androgen receptor htSNPs in relation to androgen levels and OC use in young women from high-risk breast cancer families.
- 2011
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In: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 102, s. 82-90
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Journal article (peer-reviewed)abstract
- High testosterone levels have been associated with breast cancer. BRCA1 may function as an androgen receptor (AR) co-regulator. We aimed to examine AR haplotype-tagging single-nucleotide polymorphisms (AR htSNPs) and diplotypes in relation to in vivo androgen levels, combined OC use, CAG and GGC genotypes, and BRCA1/2/X family status in 269 young healthy women from breast cancer high-risk families and 56 additional BRCA1/2 mutation carriers. Testosterone, androstenedione, dehydroepiandrosterone sulfate, and body constitution were measured on cycle days 18-23. Six AR htSNPs and CAG and GGC repeat lengths were genotyped. Most OC users had lower androgen levels than non-users (all Ps<0.0001). Rare variant diplotypes were associated with higher testosterone levels in OC users than in non-users (P(interaction)=0.011). The interaction remained after adjustment for family clustering. Neither individual AR htSNPs nor other diplotypes were significantly associated with androgen levels and did not tag for CAG or GGC genotypes. In the first included woman from each family, the odds of having the most common diplotype was lower in BRCA1 families compared to other families OR 0.41 (95% CI 0.22-0.78). In conclusion, we found few associations between AR htSNPs or diplotypes and androgen levels in women. Diplotypes cannot replace genotyping of microsatellites CAG or GGC. Since testosterone levels are not affected the same way by combined OC use among all women, young women who have higher testosterone levels during combined OC use may belong to the subgroup of women who will not be helped by combined OCs for treatment of androgen-dependent conditions and may be at higher risk for early-onset breast cancer. Whether these women can be identified with AR genotyping needs to be confirmed in an independent cohort.
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