AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

A decrease in radiative forcing and equivalent effective chlorine from hydrochlorofluorocarbons

The Montreal Protocol and its successive amendments have been successful in curbing emissions of ozone-depleting substances and potent greenhouse gases via production/consumption controls. Here, we show that the radiative forcing and equivalent effective chlorine from hydrochlorofluorocarbons has decreased from 61.75 mW m-2 and 321.69 ppt, respectively, since 2021, five years before the most recent projected decrease. This important milestone demonstrates the benefits of the Protocol for mitigating climate change and stratospheric ozone layer loss

Introduction

Abstract: —J. Blunden and T. Boyer In 2023, La Niña conditions that generally prevailed in the eastern Pacific Ocean from mid-2020 into early 2023 gave way to a strong El Niño by October. Atmospheric concentrations of Earth’s major greenhouse gases—carbon dioxide, methane, and nitrous oxide—all increased to record-high levels. The annual global average carbon dioxide concentration in the atmosphere rose to 419.3±0.1 ppm, which is 50% greater than the pre-industrial level. The growth from 2022 to 2023 was 2.8 ppm, the fourth highest in the record since the 1960s. The combined short-term effects of El Niño and the long-term effects of increasing levels of heat-trapping gases in the atmosphere contributed to new records for many essential climate variables reported here. The annual global temperature across land and oceans was the highest in records dating as far back as 1850, with the last seven months (June–December) having each been record warm. Over land, the globally averaged temperature was also record high. Dozens of countries reported record or near-record warmth for the year, including China and continental Europe as a whole (warmest on record), India and Russia (second warmest), and Canada (third warmest). Intense and widespread heatwaves were reported around the world. In Vietnam, an all-time national maximum temperature record of 44.2°C was observed at Tuong Duong on 7 May, surpassing the previous record of 43.4°C at Huong Khe on 20 April 2019. In Brazil, the air temperature reached 44.8°C in Araçuaí in Minas Gerais on 20 November, potentially a new national record and 12.8°C above normal. The effect of rising temperatures was apparent in the cryosphere, where snow cover extent by June 2023 was the smallest in the 56-year record for North America and seventh smallest for the Northern Hemisphere overall. Heatwaves contributed to the greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Due to rapid volume loss beginning in 2021, St. Anna Glacier in Switzerland and Ice Worm Glacier in the United States disappeared completely. In August, as a direct result of glacial thinning over the past 20 years, a glacial lake on a tributary of the Mendenhall Glacier in Alaska burst through its ice dam and caused unprecedented flooding on Mendenhall River near Juneau. Across the Arctic, the annual surface air temperature was the fourth highest in the 124-year record, and summer (July–September) was record warm. Smaller-than-normal snow cover extent in May and June contributed to the third-highest average peak tundra greenness in the 24-year record. In September, Arctic minimum sea ice extent was the fifth smallest in the 45-year satellite record. The 17 lowest September extents have all occurred in the last 17 years. In Antarctica, temperatures for much of the year were up to 6°C above average over the Weddell Sea and along coastal Dronning Maud Land. The Antarctic Peninsula also experienced well-above-average temperatures during the 2022/23 melt season, which contributed to its fourth consecutive summer of above-average surface melt. On 21 February, Antarctic sea ice extent and sea ice area both reached all-time lows, surpassing records set just a year earlier. Over the course of the year, new daily record-low sea ice extents were set on 278 days. In some instances, these daily records were set by a large margin, for example, the extent on 6 July was 1.8 million km2 lower than the previous record low for that day. Across the global oceans, the annual sea surface temperature was the highest in the 170-year record, far surpassing the previous record of 2016 by 0.13°C. Daily and monthly records were set from March onward, including an historic-high daily global mean sea surface temperature of 18.99°C recorded on 22 August. Approximately 94% of the ocean surface experienced at least one marine heatwave in 2023, while 27% experienced at least one cold spell. Globally averaged ocean heat content from the surface to 2000-m depth was record high in 2023, increasing at a rate equivalent to ∼0.7 Watts per square meter of energy applied over Earth’s surface. Global mean sea level was also record high for the 12th consecutive year, reaching 101.4 mm above the 1993 average when satellite measurements began, an increase of 8.1±1.5 mm over 2022 and the third highest year-over-year increase in the record. A total of 82 named tropical storms were observed during the Northern and Southern Hemispheres’ storm seasons, below the 1991–2020 average of 87. Hurricane Otis became the strongest landfalling hurricane on record for the west coast of Mexico at 140 kt (72 m s−1), causing at least 52 fatalities and $12–16 billion U.S. dollars in damage. Freddy became the world’s longest-lived tropical cyclones on record, developing into a tropical cyclone on 6 February and finally dissipating on 12 March. Freddy crossed the full width of the Indian Ocean and made one landfall in Madagascar and two in Mozambique. In the Mediterranean Sea—outside of traditional tropical cyclone basins—heavy rains and flooding from Storm Daniel killed more than 4300 people and left more than 8000 missing in Libya. The record-warm temperatures in 2023 created conditions that helped intensify the hydrological cycle. Measurements of total-column water vapor in the atmosphere were the highest on record, while the fraction of cloud area in the sky was the lowest since records began in 1980. The annual global mean precipitation total over land surfaces for 2023 was among the lowest since 1979, but global one-day maximum totals were close to average, indicating an increase in rainfall intensity. In July, record-high areas of land across the globe (7.9%) experienced extreme drought, breaking the previous record of 6.2% in July 2022. Overall, 29.7% of land experienced moderate or worse categories of drought during the year, also a record. Mexico reported its driest (and hottest) year since the start of its record in 1950. In alignment with hot and prolonged dry conditions, Canada experienced its worst national wildfire season on record. Approximately 15 million hectares burned across the country, which was more than double the previous record from 1989. Smoke from the fires were transported far into the United States and even to western European countries. August to October 2023 was the driest three-month period in Australia in the 104-year record. Millions of hectares of bushfires burned for weeks in the Northern Territory. In South America, extreme drought developed in the latter half of the year through the Amazon basin. By the end of October, the Rio Negro at Manaus, a major tributary of the Amazon River, fell to its lowest water level since records began in 1902. The transition from La Niña to El Niño helped bring relief to the prolonged drought conditions in equatorial eastern Africa. However, El Niño along with positive Indian Ocean dipole conditions also contributed to excessive rainfall that resulted in devastating floods over southeastern Ethiopia, Somalia, and Kenya during October to December that displaced around 1.5 million people. On 5 September, the town of Zagora, Greece, broke a national record for highest daily rainfall (754 mm in 21 hours, after which the station ceased reporting) due to Storm Daniel; this one-day accumulation was close to Zagora’s normal annual total