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      Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis

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          Abstract

          Background:

          An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women's cancers, even though SLE affects mostly females. Our objective was to estimate the risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population.

          Methods:

          Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained from general population data. The parameter of interest was the standardised incidence ratio (SIR), the ratio of observed to expected malignancies.

          Results:

          The five studies included 47 325 SLE patients (42 171 females) observed for 282 553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer.

          Conclusions:

          Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE ( vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.

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          Most cited references19

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          Multiple loci with different cancer specificities within the 8q24 gene desert.

          Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.
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            An international cohort study of cancer in systemic lupus erythematosus.

            There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.
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              Menstrual and reproductive factors and endometrial cancer risk: Results from a population-based case-control study in urban Shanghai.

              The purpose of our study was to evaluate the association of menstrual and reproductive factors with the risk of endometrial cancer. In a population-based case-control study conducted in urban Shanghai, in-person interviews were completed for 833 women aged 30-69 years and an equal number of controls frequency-matched to cases by age. All cases were newly diagnosed with endometrial cancer between January 1, 1997 and December 31, 2001. The unconditional logistic regression model was employed to derive the adjusted odds ratios (ORs) of endometrial cancer and 95% confidence intervals (CIs) in relation to menstrual and reproductive factors. Earlier menarche age, particularly among premenopausal women, and later menopausal age were associated with an elevated risk of endometrial cancer. A clear dose-response relation between endometrial cancer risk and years of menstruation was observed (p for trend < 0.01). Compared to women ever having a pregnancy and women ever having had a live birth, respectively, nulligravity and nulliparity were both associated with a more than one-fold elevated risk of endometrial cancer. Both completed (OR = 3.02, 95% CI 1.10-8.32 for women never having a complete pregnancy) and incomplete pregnancy (OR = 0.69, 95%CI 0.55-0.87) conferred a protective effect against endometrial cancer, and the protective effect appeared to increase with total number of pregnancies (p for trend = 0.01). The effect of pregnancy on endometrial cancer remained unchanged with increasing time since the last pregnancy. Stillbirth and age at first pregnancy was unrelated to endometrial cancer risk. Our study suggests that prolonged menstruation was related to an increased risk of endometrial cancer while pregnancy, including induced abortion, reduced the risk of endometrial cancer. Copyright 2003 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                26 April 2011
                12 April 2011
                : 104
                : 9
                : 1478-1481
                Affiliations
                [1 ]simpleDivision of Rheumatology, McGill University Health Centre , Montreal, QC, Canada
                [2 ]simpleDivision of Clinical Epidemiology, Research Institute of the McGill University Health Centre , 687 Pine Avenue West, V-Building, V2.09, Montreal, QC H3A 1A1, Canada
                [3 ]simpleDivision of Rheumatology, Northwestern University , Chicago, IL, USA
                [4 ]simpleProgram in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University , Montreal, QC, Canada
                [5 ]simpleDepartment of Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, City Hospital , Birmingham, UK
                [6 ]simpleDivision of Clinical Immunology/Allergy, McGill University Health Centre , Montreal, QC, Canada
                Author notes
                Article
                bjc2011115
                10.1038/bjc.2011.115
                3101932
                21487409
                c5f14238-bd08-4d9d-9be6-83d2221dc1b7
                Copyright © 2011 Cancer Research UK
                History
                : 02 November 2010
                : 17 February 2011
                : 11 March 2011
                Categories
                Short Communication

                Oncology & Radiotherapy
                systemic lupus,malignancy,sle
                Oncology & Radiotherapy
                systemic lupus, malignancy, sle

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