Colorectal Cancer Risks in Relatives of Young-Onset Cases: Is Risk the Same Across All First-Degree Relatives?

Boardman, Lisa A.; Morlan, Bruce W.; Rabe, Kari G.; Petersen, Gloria M.; Lindor, Noralane M.; Nigon, Sandra K.; Goldberg, Julia E.; Gallinger, Steven

doi:10.1016/j.cgh.2007.06.001

Cited by 36 publications

(33 citation statements)

References 9 publications

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“…2) consistent with the familial risk of tumors related to hereditary nonpolyposis colorectal cancer which is associated with a young age at onset. [36][37][38][39] We also found high familial aggregation of breast cancer at younger ages consistent with reports of higher prevalence of mutations in the BRCA1/BRCA2 genes in young patients and a high probability of the same gene mutations in their sisters. 40,41 Examining the changing risk with time since the index person's diagnosis, we found the pattern varied by cancer site: for colorectal and breast cancer, the risk profile for siblings was approximately constant for up to 20 years while for melanoma there was evidence of a small decline in risk in the first 5 years, and for prostate cancer a sharp decline.…”

Section: Epidemiologysupporting

confidence: 90%

“…The incidence rates differed by cancer site: for example, at age 60 years, the absolute risk (per 10,000 person years) of colorectal cancer in control siblings was 6.55 (95% CI: 5.86-7.31) compared to 16 (Table 2a). From age-stratified analysis, younger siblings had the highest IRR for colorectal cancer, breast cancer and prostate cancer, but the IRR was highest in 40-50 year old siblings for melanoma, although this was of similar magnitude to the IRR in the youngest siblings (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). The IRRs for each cancer decreased with age and were relatively stable in older ages.…”

Section: Absolute Risk Of Cancer By Agementioning

confidence: 89%

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Patterns of changing cancer risks with time since diagnosis of a sibling

Lee

Czene

Rebora

et al. 2014

Intl Journal of Cancer

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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 ...

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Section: Epidemiologysupporting

confidence: 90%

Section: Absolute Risk Of Cancer By Agementioning

confidence: 89%

Patterns of changing cancer risks with time since diagnosis of a sibling

Lee

Czene

Rebora

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

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“…In a codominant model of inheritance, an inherited predisposition to develop sessile serrated adenomas and CRC may be attributable to carriers of one allele, and the more severe phenotype associated with hyperplastic polyposis may be the result of homozygous carriers or a carrier paired with a recessive allele. Studies (35,36) have shown that CRC risk is significantly greater among siblings than for parent-offspring, which is suggestive of recessive inheritance. Interestingly, in a large populationbased study (35), the greatest CRC risk was associated with an affected sibling who had a right-sided colon cancer.…”

Section: Resultsmentioning

confidence: 99%

Increased Cancer Predisposition in Family Members of Colorectal Cancer Patients Harboring the p.V600E BRAF Mutation: a Population-Based Study

Wish¹,

Hyde²,

Parfrey³

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: The serrated pathway represents a distinct molecular pathway of colorectal carcinogenesis and is associated with the p.V600E BRAF mutation. The objective of this study is to characterize the cancer family history and clinicopathologic features of colorectal cancer (CRC) patients according to the microsatellite instability (MSI) and BRAF mutation status of their tumors.Methods: The tumors from 558 population-based CRC patients underwent pathologic examination and molecular analysis for MSI, BRAF, and germline mutations in mismatch repair genes MUTYH and APC. The cancer history in first-degree relatives (FDR) of index patients was ascertained.Results: The risk of CRC in FDRs of index patients with MSI-H BRAF mutation [hazard ratio (HR) = 2.49; 95% confidence interval (95% CI), 1.57-3.93] and microsatellite-stable BRAF mutation tumors (HR = 1.64; 95% CI, 1.01-2.66) was significantly elevated compared with FDRs of index patients with microsatellite-stable BRAF wild-type tumors. The incidence of nonmelanoma skin cancer was also significantly elevated in FDRs of patients with BRAF mutation CRC (HR = 2.52; 95% CI, 1.31-4.86). Furthermore, BRAF mutation CRC was associated with a distinct clinical, molecular, and pathologic phenotype.Conclusions: The increased incidence of cancer in FDRs of index CRC patients with the p.V600E BRAF mutation may be explained by a genetic predisposition to develop cancer through the serrated pathway of colorectal carcinogenesis.Impact: Family members of BRAF CRC patients have an increased predisposition to develop cancer. Future work should aim to identify the causative genetic factors. Cancer Epidemiol Biomarkers Prev; 19(7);

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“…It is higher in people with a stronger family history, such as a history of colorectal cancer or adenomatous polyps in any first-degree relative younger than age 60; or a history of colorectal cancer or adenomatous polyps in two or more first-degree relatives at any age. 25 The reasons for the increased risk are not clear, but it likely due to inherited genes, shared environmental factors, or some combination of these.…”

Section: Family History Of Colorectal Cancer or Adenomatous Polypsmentioning

confidence: 99%

Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors

Haggar

Boushey²

2009

Clinics in Colon and Rectal Surgery

1,749

1,346

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In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.KEYWORDS: Colorectal cancer, epidemiology, incidence, survival, risk factorsObjectives: Upon completion of this article, the reader should be able to identify epidemiologic trends in the incidence, mortality, and survival rates for colorectal cancer across different patient demographics; describe familial and hereditary risk factors associated with the development of colorectal cancer; and list dietary and lifestyle factors known to be associated with the risk of colorectal cancer. INCIDENCE OF COLORECTAL CANCERColorectal cancer is a major cause of morbidity and mortality throughout the world.1 It accounts for over 9% of all cancer incidence. 2,3 It is the third most common cancer worldwide and the fourth most common cause of death.2 It affects men and women almost equally, with just over 1 million new cases recorded in 2002, the most recent year for which international estimates are available.

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Colorectal Cancer Risks in Relatives of Young-Onset Cases: Is Risk the Same Across All First-Degree Relatives?

Cited by 36 publications

References 9 publications

Patterns of changing cancer risks with time since diagnosis of a sibling

Patterns of changing cancer risks with time since diagnosis of a sibling

Increased Cancer Predisposition in Family Members of Colorectal Cancer Patients Harboring the p.V600E BRAF Mutation: a Population-Based Study

Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors

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