Family history is a well-known risk factor for many cancers. However, it is important to know if/how the familial risk of cancer changes over time. For each of four major cancers (colorectal, breast, prostate and melanoma), we identified siblings of cancer patients (case siblings) and siblings of matched cancer-free controls sampled from Swedish population-based registers. Effects of age and time since diagnosis on sibling risks were examined using Poisson regression and presented graphically as smoothed hazard ratios (HRs). Screening effects were investigated by comparing hazards before/after the introduction of mammography for breast cancer and prostate-specific antigen (PSA) testing for prostate cancer. Case siblings had higher cancer incidence than control siblings for all cancers at all ages, with overall incidence rate ratios (IRRs) of 2.41 (95% confidence interval 2.14-2.71) for colorectal cancer, 2.37 (2.24-2.52) for breast cancer, 3.69 (3.46-3.93) for prostate cancer and 3.20 (2.72-3.76) for melanoma. Risks were highest in siblings who were young when the first cancer was diagnosed in the family, with siblings aged 30-40 having IRR 9.05 (3.03-27.00) for colorectal cancer and 4.30 (2.87-6.45) for breast cancer. Smoothed HRs remained fairly constant for up to 20 years except for prostate cancer, where the HR decreased steeply during the first few years. After introduction of PSA testing, men had higher incidence of prostate cancer shortly after diagnosis in a brother, but no such screening effect was found for breast cancer. Our findings can help inform the screening and counseling of family members of cancer patients.Family history is long recognized as an important risk factor for cancer and has also been found to be associated with cancer prognosis. One of the main, but simple, ways to begin to understand cancer etiology is by identifying the involvement of heritable genes through investigation of familial aggregation. There is a large body of published research providing estimates of increased risk for various cancer sites in different types of relatives. [1][2][3][4] However, in addition to the estimates of overall or lifetime increased risk in family members, it is important to know if/how this risk changes over time. To address this question, different time scales need to be considered when studying the relatives at risk: current age, age at the time of diagnosis of the first cancer in the family, elapsed time from the cancer diagnosis and calendar time.Age is the strongest risk factor for cancer onset and many studies show both the age of relatives and the age of the cancer patient at diagnosis to be associated with the family cancer risk. 5,6 Young age at onset of cancer has been shown to have high heritability and so is an important factor in familial risk. 7,8 However, few studies have investigated in detail how this risk changes with time since the first (index) cancer diagnosis in a family. 9 Such risk profiles would not only provide insight into underlying etiology but could also be used to ...