3,742 research outputs found
Cancer risk in patients with constitutional chromosome deletions: a nationwide British cohort study
No full textThe finding of increased risks of specific cancers in individuals with constitutional deletions of chromosomes 11p and 13q led to the discovery of cancer predisposition genes at these locations, but there have been no systematic studies of cancer risks in patients with constitutional deletions, across the chromosome complement. Therefore, we assessed cancer incidence in comparison with national cancer incidence rates in a follow-up of 2561 patients with constitutional autosomal chromosome deletions diagnosed by microscopy or fluorescence in situ hybridisation in Britain during the period 1965-2002. Thirty cancers other than non-melanoma skin cancer occurred in the cohort (standardised incidence ratio (SIR)=2.4, 95% confidence interval (CI) 1.6-3.5). There were significantly increased risks of renal cancer in persons with 11p deletions (SIR=1869, 95% CI 751-3850; P=4 x 10(-21)), eye cancer with 13q deletions (SIR=1084, 95% CI 295-2775; P=2 x 10(-11)), and anogenital cancer with 11q deletions (SIR=305, 95% CI 63-890; P=3 x 10(-7)); all the three latter cancers were in the 11 subjects with 11q24 deletions. The results strongly suggest that in addition to suppressor genes relating to Wilms' tumour risk on 11p and retinoblastoma on 13q, there are suppressor genes around 11q24 that greatly affect anogenital cancer ris
A case–control study of risk of leukaemia in relation to mobile phone use
No full textBACKGROUND: Mobile phone use is now ubiquitous, and scientific reviews have recommended research into its relation to leukaemia risk, but no large studies have been conducted. METHODS: In a case-control study in South East England to investigate the relation of acute and non-lymphocytic leukaemia risk to mobile phone use, 806 cases with leukaemia incident 2003-2009 at ages 18-59 years (50% of those identified as eligible) and 585 non-blood relatives as controls (provided by 392 cases) were interviewed about mobile phone use and other potentially aetiological variables. RESULTS: No association was found between regular mobile phone use and risk of leukaemia (odds ratio (OR)=1.06, 95% confidence interval (CI)=0.76, 1.46). Analyses of risk in relation to years since first use, lifetime years of use, cumulative number of calls and cumulative hours of use produced no significantly raised risks, and there was no evidence of any trends. A non-significantly raised risk was found in people who first used a phone 15 or more years ago (OR=1.87, 95% CI=0.96, 3.63). Separate analyses of analogue and digital phone use and leukaemia subtype produced similar results to those overall. CONCLUSION: This study suggests that use of mobile phones does not increase leukaemia risk, although the possibility of an effect after long-term use, while biologically unlikely, remains open
Effect of population breast screening on breast cancer mortality up to 2005 in England and Wales: an individual-level cohort study
No full textBACKGROUND: Population breast screening has been implemented in the UK for over 25 years, but the size of benefit attributable to such programmes remains controversial. We have conducted the first individual-based cohort evaluation of population breast screening in the UK, to estimate the impact of the NHS breast screening programme (NHSBSP) on breast cancer mortality. METHODS: We followed 988 090 women aged 49-64 years in 1991 resident in England and Wales, who because of the staggered implementation of the NHSBSP, included both invited subjects and an uninvited control group. Individual-level breast screening histories were linked to individual-level mortality and breast cancer incidence data from national registers. Risk of death from breast cancer was investigated by incidence-based mortality analyses in relation to intention to screen and first round attendance. Overdiagnosis of breast cancer following a single screening round was also investigated. RESULTS: Invitation to NHSBSP screening was associated with a reduction in breast cancer mortality in 1991-2005 of 21% (RR=0.79, 95% CI: 0.73-0.84, P<0·001) after adjustment for age, socioeconomic status and lead-time. Breast cancer deaths among first invitation attenders were 46% lower than among non-attenders (RR=0.54, 95% CI: 0.51-0·57, P<0.001) and 32% lower following adjustment for age, socioeconomic status and self-selection bias (RR=0.68, 95% CI: 0.63-0·73, P<0.001). There was little evidence of overdiagnosis associated with invitation to first screen. CONCLUSIONS: The results indicate a substantial, statistically significant reduction in breast cancer mortality between 1991 and 2005 associated with NHSBSP activity. This is important in public health terms
Genome-wide homozygosity signature and risk of Hodgkin lymphoma.
No full textRecent studies have reported that regions of homozygosity (ROH) in the genome are detectable in outbred populations and can be associated with an increased risk of malignancy. To examine whether homozygosity is associated with an increased risk of developing Hodgkin lymphoma (HL) we analysed 589 HL cases and 5,199 controls genotyped for 484,072 tag single nucleotide polymorphisms (SNPs). Across the genome the cumulative distribution of ROH was not significantly different between cases and controls. Seven ROH at 4q22.3, 4q32.2, 7p12.3-14.1, 7p22.2, 10p11.22-23, 19q13.12-2 and 19p13.2 were associated with HL risk at P < 0.01. Intriguingly 4q22.3 harbours an ROH to which the nuclear factor NF-kappa-B p105 subunit (NFKB1) maps (P = 0.002). The ROH at 19q13.12-2 has previously been implicated in B-cell precursor acute lymphoblastic leukaemia. Aside from these observations which require validation, it is unlikely that levels of measured homozygosity caused by autozygosity, uniparental isodisomy or hemizygosity play a major role in defining HL risk in predominantly outbred populations
Maternal breast cancer risk in relation to birthweight and gestation of her offspring
No full textAbstract Background Parity and age at first pregnancy are well-established risk factors for breast cancer, but the effects of other characteristics of pregnancies are uncertain and the literature is inconsistent. Methods In a cohort of 83,451 parous women from the general population of the UK, which collected detailed information on each pregnancy and a wide range of potential confounders, we investigated the associations of length of gestation and birthweight of offspring in a woman’s pregnancies with her breast cancer risk, adjusting for a full range of non-reproductive as well as reproductive risk factors unlike in previous large studies. Results Gestation of the first-born offspring was significantly inversely related to the risk of pre-menopausal breast cancer (p trend = 0.03; hazard ratio (HR) for 26–31 compared with 40–41 weeks, the baseline group, = 2.38, 95% confidence interval (CI) 1.26–4.49), and was borderline significantly related to risk of breast cancer overall (p trend = 0.05). Risk was significantly raised in mothers of high birthweight first-born (HR for breast cancer overall = 1.53, 95% CI 1.06–2.21 for ≥ 4500 g compared with 3000–3499 g, the baseline group). For gestation and birthweight of most recent birth, there were no clear effects. Analyses without adjustment for confounders (other than age) gave similar results. Conclusions Our data add to evidence that short gestation pregnancies may increase the risk of breast cancer, at least pre-menopausally, perhaps by hormonal stimulation and breast proliferation early in pregnancy without the opportunity for the differentiation that occurs in late pregnancy. High birthweight first pregnancies may increase breast cancer risk, possibly through the association of birthweight with oestrogen and insulin-like growth factor 1 levels
On the AJ Conjecture for Knots
No full textWe confirm the AJ conjecture [Ga2] that relates the A-polynomial and the colored Jones polynomial for hyperbolic knots satisfying certain conditions. In particular, we show that the conjecture holds true for some classes of two-bridge knots and pretzel knots. This extends the result of the first author in [Le2], who established the AJ conjecture for a large class of two-bridge knots, including all twist knots. Along the way, we explicitly calculate the universal SL₂(C)-character ring of the knot group of the (−2, 3, 2n + 1)-pretzel knot, and show it is reduced for all integers n
Mortality and Cancer Incidence in Carriers of Balanced Robertsonian Translocations: A National Cohort Study.
No full textA balanced robertsonian translocation (rob) results from fusion of 2 acrocentric chromosomes. Carriers are phenotypically normal and are often diagnosed because of recurrent miscarriages, infertility, or aneuploid offspring. Mortality and site-specific cancer risks in carriers have not been prospectively investigated. We followed 1,987 carriers diagnosed in Great Britain for deaths and cancer risk, over an average of 24.1 years. Standardized mortality and incidence ratios were calculated comparing the number of observed events against population rates. Overall mortality was higher for carriers diagnosed before age 15 years (standardized mortality ratio (SMR) = 2.00, 95% confidence interval (CI): 1.09, 3.35), similar for those diagnosed aged 15-44 years (SMR = 1.06, 95% CI: 0.86-1.28), and lower for those diagnosed aged 45-84 years (SMR = 0.81, 95% CI: 0.68, 0.95). Cancer incidence was higher for non-Hodgkin lymphoma (standardized incidence ratio (SIR) = 1.90, 95% CI: 1.01, 3.24) and childhood leukemia (SIR = 14.5, 95% CI: 1.75, 52.2), the latter particularly in rob(15;21) carriers (SIR = 447.8, 95% CI: 11.3, 2,495). Rob(13;14) carriers had a higher breast cancer risk (SIR = 1.58, 95% CI: 1.12, 2.15). Mortality risks relative to the population in diagnosed carriers depend on age at cytogenetic diagnosis, possibly reflecting age-specific cytogenetic referral reasons. Carriers might be at greater risk of childhood leukemia and non-Hodgkin lymphoma and those diagnosed with rob(13;14) of breast cancer
Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: A prospective study.
No full textThe constitutional t(11;22)(q23;q11) translocation is the only recurrent non-Robertsonian translocation known in humans. Carriers are phenotypically normal and are usually referred for cytogenetic testing because of multiple miscarriages, infertility, or having aneuploidy in offspring. A breast cancer predisposition has been suggested, but previous studies have been small and had methodological shortcomings. We therefore conducted a long-term prospective study of cancer and mortality risk in carriers. We followed 65 male and 101 female carriers of t(11;22)(q23;q11) diagnosed in cytogenetic laboratories in Britain during 1976-2005 for cancer and deaths for an average of 21.4 years per subject. Standardised mortality (SMR) and incidence (SIR) ratios were calculated comparing the numbers of observed events with those expected from national age-, sex-, country- and calendar-period-specific population rates. Cancer incidence was borderline significantly raised for cancer overall (SIR = 1.56, 95% CI: 0.98-2.36, n = 22), and significantly raised for invasive breast cancer (SIR = 2.74, 95% CI: 1.18-5.40, n = 8) and in situ breast cancer (SIR = 13.0, 95% CI: 3.55-33.4, n = 4). Breast cancer risks were particularly increased at ages <50 (SIR = 4.37, 95% CI: 1.42-10.2 for invasive, SIR = 22.8, 95% CI: 2.76-82.5 for in situ). Mortality was borderline significantly raised for breast cancer (SMR = 4.82, 95% CI: 0.99-14.1) but not significantly raised for other cancers or causes. Individuals diagnosed with t(11;22)(q23;q11) appear to be at several-fold increased breast cancer risk, with the greatest risks at premenopausal ages. Further research is required to understand the genetic mechanism involving 11q23 and 22q11 and there may be a need for enhanced breast cancer surveillance among female carriers
Discovery of a single faint AGN in a large sample of z > 5 Lyman break galaxies
No full textAs part of a large spectroscopic survey of z > 5 Lyman break galaxies (LBGs), we have identified a single source which is clearly hosting an active galactic nucleus (AGN). Out of a sample of more than 50 spectroscopically confirmed R-band dropout galaxies at z∼ 5 and above, only J104048.6−115550.2 at z= 5.44 shows evidence for a high ionization potential emission line indicating the presence of a hard ionizing continuum from an AGN. Like most objects in our sample the rest-frame-UV spectrum shows the UV continuum breaking across a Lyα line. Uniquely within this sample of LBGs, emission from N V is also detected, a clear signature of AGN photoionization. The object is spatially resolved in Hubble Space Telescope (HST) imaging. This, and the comparatively high Lyα/N V flux ratio indicates that the majority of the Lyα (and the UV continuum longward of it) originates from stellar photoionization, a product of the ongoing starburst in the LBG. Even without the AGN emission, this object would have been photometrically selected and spectroscopically confirmed as a Lyman break in our survey. The measured optical flux (IAB= 26.1) is therefore an upper limit to that from the AGN and is of order 100 times fainter than the majority of known quasars at these redshifts. The detection of a single object in our survey volume is consistent with the best current models of high redshift AGN luminosity function, providing a substantial fraction of such AGN is found within luminous starbursting galaxies. We discuss the cosmological implications of this discovery
Smoking and risk of breast cancer in the Generations Study cohort
No full textAbstract Background Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent. Methods We used serial questionnaire information from the Generations Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake. Results Among 102,927 women recruited 2003–2013, with an average of 7.7 years of follow-up, 1815 developed invasive breast cancer. The HR (reference group was never smokers) was 1.14 (95% CI 1.03–1.25; P = 0.010) for ever smokers, 1.24 (95% CI 1.08–1.43; P = 0.002) for starting smoking at ages < 17 years, and 1.23 (1.07–1.41; P = 0.004) for starting smoking 1–4 years after menarche. Breast cancer risk was not statistically associated with interval from initiation of smoking to first birth (P-trend = 0.97). Women with a family history of breast cancer (ever smoker vs never smoker HR 1.35; 95% CI 1.12–1.62; P = 0.002) had a significantly larger HR in relation to ever smokers (P for interaction = 0.039) than women without (ever smoker vs never smoker HR 1.07; 95% CI 0.96–1.20; P = 0.22). The interaction was prominent for age at starting smoking (P = 0.003) and starting smoking relative to age at menarche (P = 0.0001). Conclusions Smoking was associated with a modest but significantly increased risk of breast cancer, particularly among women who started smoking at adolescent or peri-menarcheal ages. The relative risk of breast cancer associated with smoking was greater for women with a family history of the disease
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