Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures

Household quarantine of second degree contacts is an effective non-pharmaceutical intervention to prevent tertiary cases in the current SARS-CoV pandemic

Background!#!Given the characteristics of SARS-CoV2 with regard to transmission before the onset of symptoms and varying manifestation indices according to age, isolation and quarantine have limited efficacy in the current pandemic. Household quarantine in second degree contacts (Hh-Q2°) outside the case household has so far only been addressed by modellers. In the literature there is no publication based on field data.!##!Methods!#!In a retrospective cohort study on real field data from a county health department (CHD), all PCR-confirmed cases and related contact persons put into quarantine were analysed. Hh-Q2° was used in our CHD from the onset of the pandemic.!##!Results!#!From 9 March to 8 December 2020, 353 PCR-confirmed cases were registered in the CHD Ploen, Northern Germany: 225 (63.7%) primary, 107 (30.3%) secondary and 21 (5.9%) tertiary cases. The 107 secondary cases resulted out of 470 (22.8%) close or 1°contacts and 21 tertiary cases out of 179 (11.7%) indirect or 2°contacts put into quarantine. The efficacy of Hh-Q2° was 51.5% (11.7%/22.8%) of that of quarantine in 1°contacts; 16.4% of all converted cases in quarantined persons were ascertained by Hh-Q2°. One in ten 1°contacts in households with tertiary cases remained asymptomatic.!##!Conclusion!#!The impact of Hh-Q2° in preventing further spread of SARS-CoV2 was considerable. With half the conversion rate in 2°contacts compared to 1°contacts, the efficacy of Hh-Q2° is substantial. Hh-Q2° should definitely be used routinely to control the spread of SARS-CoV2 more efficiently and national authorities should include it in their guidelines

Vaccine-masked spread of SARS-CoV2 in an elderly care home, and how to prevent a spill-over into the general population

Aim!#!The vaccination campaign against SARS-CoV2 in Germany started at the peak of the second wave. An outbreak in an elderly care home occurred in our county at the time of the second vaccination. We describe a package of measures to control the outbreak and to prevent a spill over into the general population.!##!Subjects and methods!#!After outbreak confirmation, a package of measures such as quarantine of the elderly care home, staff and visitors, and their households was implemented. By sequential testing, quarantine measures were lifted. Surveillance of staff and residents by rapid antigen test and symptom monitoring was used in parallel.!##!Results!#!The outbreak was on-going for around 17 days until it was noticed by a symptomatic external staff member as index case. A total of 23 out of 96 residents (24.0%) and nine out of 114 staff (7.9%) were infected. Three residents died. Effective first-dose vaccine coverage was 85.4% in residents, 27.4% in internal, and 10.5% in external staff. Given the long latency period, the use of household quarantine prevented a spill over into the public. Already 16 days after notification of the index case the outbreak could be declared over.!##!Conclusions!#!Interferences between vaccination coverage and outbreak characteristics in regard to an extended latency period were observed. Household quarantine of case as well as contact households is of increased importance in the era of vaccination to prevent further spread into the general population until population-based control measures and lockdowns can be lifted

No temporal association between influenza outbreaks and invasive pneumococcal infections

OBJECTIVE: To assess whether the influenza peak in populations precedes the annual peak for invasive pneumococcal infections (IPI) in winter. DESIGN: Ecological study. Active surveillance data on influenza A and IPI in children up to 16 years of age collected from 1997 to 2003 were analysed. SETTING: Paediatric hospitals in Germany. Patients: Children under 16 years of age. RESULTS: In all years under study, the influenza A season did not appear to affect the IPI season (p = 0.49). Specifically, the influenza peak never preceded the IPI peak. CONCLUSION: On a population level there was no indication that the annual influenza epidemic triggered the winter increase in the IPI rate or the peak of the IPI distribution in children

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer

Background & Aims: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. Methods: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. Results: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28–4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80–3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10–5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61–5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70–3.00). Sensitivity analyses were consistent with these findings. Conclusions: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.</p

Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer

Epub 2019 Dec 1