Sex Ratio Among the Offspring of BRCA Mutation Carriers

Sex Ratio Distortion in Offspring of Families with BRCA1 or BRCA2 Mutant Alleles: An Ascertainment Bias Phenomenon?

“…Our data expand upon the work by Feunteun et al [6] and Struewing et al [5]. Our analysis assessed whether or not the imbalances in sex-ratio among the offspring of BRCA1 and BRCA2 carriers persisted when the effects of ascertainment bias were removed.…”

“…While Gal et al [9] did not find differences in the male-to-female offspring ratio in Ashkenazi Jewish women with BRCA1 or BRCA2 mutations, two other papers reported an excess of females among the offsprings of both BRCA1 and BRCA2 mutation carriers [5,6]. Both reports attempted to minimize the impact of different ascertainment bias by analyzing specific sub-cohorts in their studies (i.e., offspring sex-ratio of male mutation carriers without affected daughters).…”

Impact of BRCA mutations on female fertility and offspring sex ratio

“…de la Hoya et al (2003) reported sex ratio distortions in BRCA1 families only; we found an excess of females among the offspring of female carriers of both BRCA1 and BRCA2 mutations although the ratios were more skewed among the offspring of BRCA1 carriers. While subsequent studies attributed the observed sex ratio distortions in BRCA families to possible confounding by ascertainment and/or selection biases (Domchek et al, 2005;Feunteun et al, 2004;Mealiffe, 2003), it is unlikely that either of these sources of bias would have influenced our results. Details of our study design have been published elsewhere (Moslehi et al, 2000).…”

“…Studies of the impact of BRCA mutations on offspring sex ratios have produced equivocal results. While an earlier study reported distorted sex ratios against male births in BRCA1 families (de la Hoya et al, 2003), subsequent studies either failed to verify the initial findings of skewed sex ratios or attributed the observed distortions to bias (Domchek et al, 2005;Feunteun et al, 2004;Mealiffe, 2003). Ascertainment bias (ascertainment through female probands and/or based on a family history) and/or selec-tion bias (higher likelihood of females with daughters participating in cancer genetic studies) were suggested to be responsible for findings of excess females in BRCA1 families (Domchek et al, 2005;Feunteun et al, 2004;Mealiffe, 2003).…”

Selected aspects of genetic counselling for BRCA1 mutation carriers

“…It is well known that studies such as these may be influenced by possible ascertainment biases [ 45 ], in particular if women with daughters are more likely to seek genetic testing than women with only boys or with no children. Recently, several authors observed only slight, statistically insignificant excesses of female offspring of BRCA1 or BRCA2 carriers, suggesting that the observed sex ratio skew against male births might be due to ascertainment bias [ 41 - 44 ]. Studies in which BRCA carriers are ascertained within a consecutive series of breast or ovarian cancer cases, and are unselected for family histories and for sex distribution of children, are ideally suited to study this question as they are free from ascertainment bias [ 35 ].…”