The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Implications for the dating of Wisconsinan (Weichselian) late-glacial events of systematic radiocarbon age differences between terrestrial plant macrofossils from a site in SW Ireland

AMS radiocarbon dates were obtained from Salix herbacea leaves, Carer seeds, and bulk organic detritus from a lake sediment profile of Wisconsinan (Weichselian) Lateglacial age in SW Ireland. There is a systematic age difference between the dated series from the two types of macrofossils, with ages obtained from Salix herbacea leaves being 900 to 1500 C-14 years younger than those obtained from Carer seeds. The latter tend to be more in accord with dates from the total organic detritus in the lake sediment, although the bulk organic fraction invariably registered the older ages. Intact survival of the fragile Salix leaves indicates that they are unlikely to have been physically transferred within the sediment matrix and/or otherwise reworked from the surrounding catchment, Hence, these macrofossils are the more likely to be contemporaneous with the time of deposition, However, there is no significant correlation between measured C-14 age and depth in the Salix values, which scatter over a range of 700 C-14 years. In contrast, the age/depth relationship for Carer shows a significant reversal, possibly reflecting the redeposition of these macrofossils, and therefore giving radiocarbon ages that are anomalously old, The data have important implications for the dating of lake sediment sequences by AMS radiocarbon measurement of terrestrial plant macrofossils

A coherent high-precision radiocarbon chronology for the Late- glacial sequence at Sluggan Bog, Co. Antrim, Northern Ireland

Seventy-five radiocarbon dates are presented from Sluggan Bog in Co. Antrim, Northern Ireland. The Holocene peats are underlain by Late-glacial sediments, which also appear to have accumulated largely in a mire environment. The radiocarbon dates, from the Late-glacial and early Holocene part of the profile, were obtained from the humic and humin fractions of the sedimentary matrix, and from plant macrofossils. The last- named were dated by AMS and the sediment samples by radiometric (beta counting) methods. Age-depth models for the three dating series show a very high level of agreement between the two fractions and the macrofossils. No statistically significant difference is found between the beta counting and AMS results. Three tephras were located in the profile, the uppermost of which is in a stratigraphical position Suggestive of the Vedde Ash, but the geochemical and radiocarbon evidence do not support this interpretation. The lower ashes are in the correct stratigraphical position for the Laacher See and Borrobol tephras, attributions substantiated by the radiocarbon evidence, but not by the geochemical data. The Sluggan sequence has generated one of the most internally consistent radiocarbon chronologies for any Late-glacial site in the British Isles, and it is suggested that in future more effort should be devoted to the search for, and analysis of, Late-glacial mire sequences, rather than the limnic records that have formed the principal focus of Late-glacial investigations hitherto

Devensian Lateglacial environmental changes in Britain: a multi-proxy environmental record from Llanilid, South Wales, UK

A multi-proxy environmental record for the Devensian (Weichselian) Lateglacial and early Holocene periods, which includes pollen, plant macrofossil, coleopteran, geochemical and stable-isotope data, is described from a site at Llanilid, South Wales, UK. The geochronology of the sequence is derived from two age-depth models which show a broad measure of agreement over much of the profile. This data set provides the basis for a detailed reconstruction of changing environmental conditions in western Britain during the transition from the Last Cold Stage to the present (Holocene) interglacial (ca 15,000-10,000 cal yr BP). Two marked cooling episodes are recorded during the course of the Lateglacial Interstadial (Greenland Interstadial 1), with mean July temperatures falling by more than 5[deg]C from a maximum of around 20[deg]C during the early Interstadial, and by a further 4-5[deg]C around 13,100 cal yr BP. The initial drop in temperature led to a reduction in Juniperus scrub, while the second, and more abrupt temperature decline resulted in a significant contraction in areas of Betula woodland. A relatively slight and short-lived warming during the later Interstadial enabled tree birch to expand once again. Mean July temperatures of 10-11[deg]C characterised the Loch Lomond/Younger Dryas Stadial (Greenland Stadial 1) between ca 12,600 and 11,400 cal yr BP, during which time a scrub tundra with Betula, Salix and a range of open-habitat taxa became established locally. The onset of the Holocene Interglacial at ca 11,400 cal yr BP is marked by an abrupt temperature rise of the order of 9[deg]C, and by the rapid expansion of Betula woodland. The Llanilid palaeoclimate record is similar to that from the Gransmoor site in northeast England, and also to the climatic sequence inferred from the GRIP ice core, particularly during the later part of the Lateglacial Interstadial (ca 14,000-12,600 cal yr BP), during the Loch Lomond/Younger Dryas Stadial and in the early Holocene. The Llanilid chronology is less secure during the early part of the Lateglacial Interstadial (pre-14,000 cal yr BP), but it is possible that warming may have begun earlier in this part of western Britain than in Greenland

Formal subdivision of the Holocene Series/Epoch: A Discussion Paper by a Working Group of INTIMATE (Integration of ice-core, marine and terrestrial records) and the Subcommission on Quaternary Stratigraphy (International Commission on Stratigraphy).

This discussion paper, by a Working Group of INTIMATE (Integration of ice-core, marine and terrestrial records) and the Subcommision on Quaternary Stratigraphy (SQS) of the International Commission on Stratigraphy (ICS), considers the prospects for a formal subdivision of the Holocene Series/Epoch. Although previous attempts to subdivide the Holocene have proved inconclusive, recent developments in Quaternary stratigraphy, notably the definition of the PleistoceneHolocene boundary and the emergence of formal subdivisions of the Pleistocene Series/Epoch, mean that it may be timely to revisit this matter. The Quaternary literature reveals a widespread but variable informal usage of a tripartite division of the Holocene (early, middle or mid, and late), and we argue that this de facto subdivision should now be formalized to ensure consistency in stratigraphic terminology. We propose an EarlyMiddle Holocene Boundary at 8200 a BP and a MiddleLate Holocene Boundary at 4200 a BP, each of which is linked to a Global Stratotype Section and Point (GSSP). Should the proposal find a broad measure of support from the Quaternary community, a submission will be made to the International Union of Geological Sciences (IUGS), via the SQS and the ICS, for formal ratification of this subdivision of the Holocene Series/Epoch. Copyright (C) 2012 John Wiley & Sons, Ltd