The interval between cancer diagnosis among mothers and offspring in a population-based cohort
ABSTRACT Familial cancers may be due to shared genes or environment, or chance aggregation. We explored the possibility that ascertainment bias influences cancer detection in families, bearing upon the time interval between diagnosis of affected mothers and offspring.
The Jerusalem Perinatal Study (JPS) comprises all mothers (n = 39,734) from Western Jerusalem who gave birth 1964 -1976 and their offspring (n = 88,829). After linking identification numbers with Israel's Cancer Registry we measured the absolute time interval between initial cancer diagnoses in affected mother-offspring pairs. We tested the probability of obtaining intervals as short as those observed by chance alone, using a permutation test on the median interval.
By June 2003 cancer had developed in 105 mother-offspring pairs within the cohort. Common sites among mothers were breast (47%), colorectal (9%), non-Hodgkin lymphoma (NHL) (8%) and cervix (7%), while for offspring in affected pairs common cancers were leukemia (12.4%), thyroid (13.3%), NHL (10.5%), breast (10.5%) and melanoma (7.6%). The median interval between diagnoses was 5.9 years, but for 33% of affected pairs the interval was < or =3 years. The probability of this occurring by chance alone was 0.03. This held true whether the offspring's or mother's diagnosis was first (P < 0.01).
In a population-based cohort followed for three decades, the absolute interval between the diagnosis of cancer in mothers and their offspring is shorter than expected by chance. Explanations include shared environmental exposures or the possibility that cancer ascertainment in one pair member affects health behaviors in the other resulting in early diagnosis. The latter may bias the estimation of anticipation and survival in familial cancers.
Full-textDOI: · Available from: Lisa Deutsch, Jun 02, 2015
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ABSTRACT: Women who have had a first-degree relative diagnosed with breast cancer (ie, a positive family history) have a rate of breast cancer that is approximately twice that of all women their age, but it is unclear how they should perceive this risk at different ages or if they should be considered at higher risk for the remainder of their lifetime. We used Swedish population-based data to assess the risk of breast cancer in 23,654 sisters of women diagnosed with breast cancer and in 1,732,775 sisters of unaffected women from 1958 through 2001. Poisson models were used to express the rate of breast cancer as a function of current age, whether a woman had an affected sister, time since the first diagnosis in the family, and family size (number of sisters). The effect of the age of the index case (the first sister diagnosed in the family) at diagnosis and whether her "at-risk" sisters had achieved this age were examined in stratified analyses. Incidence rate ratios of breast cancer in exposed compared with unexposed sisters were calculated with 95% confidence intervals. All estimates were adjusted for calendar time. Sisters of breast cancer patients had higher breast cancer incidence than unexposed sisters at all ages. The association of exposure (ie, a diagnosis of breast cancer in a sister) with the risk of breast cancer was most pronounced in young women (age 20-39; incidence rate ratio = 6.64, 95% confidence interval = 4.66 to 9.48), and the relative risk decreased to approximately 2 in women older than 50 years. The risk associated with having a sister diagnosed with breast cancer was not modified substantially by the age of the index case at diagnosis (< or = 45 years vs > 45 years). The risk was similar for women who were approaching the age at which the first sister was diagnosed in their family and those who had already attained it. The incidence rate ratio of breast cancer in exposed sisters compared with unexposed sisters was constant over time for all age categories of at-risk women. Women who have a sister diagnosed with breast cancer have an increased risk of breast cancer throughout much of their lifetimes.CancerSpectrum Knowledge Environment 05/2008; 100(10):721-7. DOI:10.1093/jnci/djn146 · 15.16 Impact Factor
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ABSTRACT: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations. Of the 132 BRCA-positive women with breast cancer who participated in a high-risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 106 women could be paired with a family member in the previous generation (Gen 1) who was diagnosed with a BRCA-related cancer (either breast cancer or ovarian cancer). Age at diagnosis, location of the mutation, and year of birth were recorded. A previously published parametric anticipation model was applied in these genetically predisposed families. The median age of cancer diagnosis was 42 years (range, 28-55 years) in Gen 2 and 48 years (range, 30-72 years) in Gen 1 (P < .001). [corrected]. In the parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years (P < .0001). Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families. Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations. The authors concluded that patients who are younger at the onset of BRCA-related cancers should continue to be tracked to offer appropriate screening modalities at appropriate ages.Cancer 01/2012; 118(2):321-5. DOI:10.1002/cncr.26284 · 4.90 Impact Factor
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