The importance of informing family members of a positive result

Hereditary pathogenic variants (mutations) are relatively rare and most individuals that get tested with GeneMate® will test negative – meaning that they will not have an increased risk of developing cancer. Some, however, will test positive – meaning that GeneMate® will identify a hereditary pathogenic variant in one of the analyzed genes. In this blog post we will walk you through what is important to think about in case of a positive result, both for your own sake and for your family members’.

All first-degree family members (parents, siblings, and children) of a carrier of a pathogenic variant in most cases have a 50% risk of being carriers themselves, regardless of whether the variant is inherited from a man or a woman. There are no variants that skip generations or that are only inherited by women or men. The variant can, however, newly occur in an individual (de novo variant) rather than being inherited. In this case only children of the individual carrying the pathogenic variant have a 50% risk of being carriers. Other relatives will not be carriers.

When the carrier status in first-degree relatives is unknown (i.e. before testing), second-degree relatives have half the risk of a first-degree relative of being carrier, or 25%. Second-degree relatives constitute grandparents, aunts, uncles, and grandchildren. Third-degree relatives, such as cousins, have a 12.5% risk of being carriers.

The importance of informing relatives

In order for your relatives to find out that they are carriers, they must first know that they have a risk of being a carrier. According to Swedish law, neither the health care provider nor iCellate are allowed to inform relatives of identified carriers. The carrier themselves must notify relatives. A Swedish study from 2020 shows public support for health care providers informing relatives, which most likely would give more people access to such information.

According to research, it can be hard to inform relatives that they have a risk of being carriers of a pathogenic variant, especially if they are distant relatives. Significantly more first-degree relatives are informed, compared to third-degree relatives. Some factors that make informing relatives harder are family conflict, resistance to making others upset, or fear of being the bearer of bad news.

In addition, it can be difficult to give relatives the correct information and for relatives to understand what it means to be a carrier. The person giving the information may miss some information, perhaps in order to protect their relatives, or because they have themselves forgotten or misunderstood some of the information received when informed about the result. Male relatives are informed to a lesser extent about pathogenic variants in BRCA1 and BRCA2, which are primarily associated with a high risk of breast and ovarian cancer, compared to female relatives. Furthermore, significantly more female relatives get tested for carrier status even in cases when male and female relatives are informed to the same extent. This despite the fact that sons and daughters to men with a pathogenic variant in BRCA1 and BRCA2 have the same risk of being a carrier and passing the variant on to their children. This pinpoints the difficulty in understanding one’s individual risk of cancer and that being a carrier has consequences for relatives, in particular one’s children, siblings, and parents.

Carrier testing

If a person tests positive for a pathogenic variant in any of the genes included in GeneMate®, iCellate can refer that person to the appropriate health care provider. The reason for the referral is for the high-risk individual(s) to access preventive measures and for relatives to be offered carrier testing. Carrier testing only tests relatives for the specific pathogenic variant that was found in the initial screening.

Relatives that test negative, meaning that they do not carry the pathogenic variant, have no increased risk of cancer. Children to individuals that test negative cannot be carriers. Parents and siblings to that individual, however, can still be carriers.

Relatives that test positive will on the other hand have an increased risk of cancer. Children, parents, and siblings of carriers have an 50% risk of being a carrier as well.

Screening programs

GeneMate® tests 41 genes that are clinically actionable. This means that a pathogenic variant in one of these genes qualifies you for screening programs and your family members for carrier testing offered by the public health care system. The type of screening offered will depend on the gene in which the pathogenic variant is located, age, and gender. Women with a pathogenic variant in BRCA1 or BRCA2, for example, are offered screening for breast and ovarian cancer. Men on the other hand are only offered screening for prostate cancer in case of a pathogenic variant in BRCA2 and not in BRCA1. In case of hereditary colorectal cancer, colonoscopy is offered to both men and women.

Preimplantation genetic testing

Another benefit of knowing that you are a carrier of a pathogenic variant is the possibility of ensuring it is not passed on to future children. In most Swedish health care regions, preimplantation genetic testing is offered, meaning that conception takes place outside of the uterus (in vitro fertilization, IVF) and only embryos that are not carriers of the pathogenic variant are inserted in the uterus. This method can help eliminate the risk of hereditary cancer in future generations.