Search

Lynch syndrome (LS), Lynch‐like syndrome (LLS) and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterise and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. Our study may support the development of risk‐adapted surveillance policies in LS, LLS and FCCX. What's new? While associations between colorectal cancer (CRC) risk and Lynch syndrome (LS) are well‐described, less is known about CRC risks linked to the closely related Lynch‐like syndrome (LLS) and familial colorectal cancer type X (FCCX). In this prospective follow‐up study of patients with LS, LLS, and FCCX, risks were similar for colorectal adenomas but considerably different for first and metachronous CRCs. In addition, LS females who carried MSH2 mutations had notably higher CRC risks than female MLH1 mutation carriers. The identification of variations in carcinogenic pathways between LS, LLS, and FCCX could enable risk‐adapted CRC surveillance for these syndromes. [ABSTRACT FROM AUTHOR]

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age‐dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person‐years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8–70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1–56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9–20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9–29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2–19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8–6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6–31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4–12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2–5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk. What's new? Women with a family history of breast cancer often have relatives who test negative for pathogenic BRCA1/2 mutations. Compared to BRCA1/2‐positive women, however, little is known about breast cancer risk among women from BRCA1/2‐negative families. In this study of women with and without BRCA1/2 mutations who participated in a German breast imaging surveillance program between 2005 and 2017, risk of first breast cancer was markedly lower in BRCA1/2‐negative women compared to BRCA1/2 mutation carriers. Relative to the general population, unilateral breast cancer risk was elevated in BRCA1/2‐negative women, while contralateral breast cancer risk was similar between the two groups. [ABSTRACT FROM AUTHOR]