Genetic Cancers Could be More Likely for Individuals With Any Family History

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“Any family history of cancer could well be relevant” for individuals who may not realize they could be at risk for genetic cancer, according to an expert.

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Any family history of cancer can be relevant, an expert said.

Individuals who have a family history of cancer may be more susceptible to developing cancer based on genetics, as one expert explained to CURE®.

People with certain pathogenic variants, defined by National Cancer Institute as genetic mutations or a change in the DNA sequence of an inherited gene in which a person may be more susceptible to developing a disease, may be at risk for developing a genetic cancer.

However, people with pathogenic variants could also have a decreased risk of developing cancer if they do not have a first-degree relative (FDR) — such as a parent or sibling — with a history of cancer, according to a study from The Lancet.

Two copies of the genes BRCA1 (gene on chromosome 17 that helps suppress cell growth) and BRCA2 (gene on chromosome 13 that helps suppress cell growth) are present in everyone, but one copy of these genes is inherited by an individual’s mother and father, National Cancer Institute described. The authors from the respective study noted that having an FDR with a history of cancer could also increase an individual’s risk of cancer.

Leigh Jackson, a lecturer in genomic medicine at the University of Exeter in England and a co-author of the study, urged people to not only speak with a medical professional, but to also speak with family members to ask about possible history of cancer.

“Speak to a medical professional, ask about family history, speak to your family members find out if they know any information, and it's not just about breast cancer; this is the thing with these inherited cancer syndromes, they cause lots of different cancers,” said Jackson.

“Some people think, ‘Oh, I don’t have a family history that’s relevant here.’ But actually, any family history of cancer could well be relevant,” he said. “So, feed all that information to your medical health professional and allow them to use that information to tailor their risk communication to you so that you're making more informed choices before you go forwards.”

Jackson also acknowledged that some individuals might not have spoken with relatives about possible family history of cancer or known that they could be at risk of developing cancer based on genetics.

“What we're concerned about and what we're seeing now is people that don't know that they've got (pathogenic variants) and so they get this genetic (testing). And this is the first they've heard about it, but they don't have any family members. With inherited cancer, they don't know they've got this syndrome in the family,” he said. “And then they get this information. And so, in those situations, anecdotally what we hear it's quite variable, because they've got no frame of reference, really, they might do nothing with this information, they might go to their primary care physician … and ask for advice.”

Nonetheless, Jackson noted that an individual who found out about their risk of developing a form of genetic cancer could face disparities regarding access to preventative options.

“Up to the extreme, they might think, ‘Well, I already know about BRCA, it’s really serious, it’s really bad. I’ve heard about this before.’ And they might go directly to a surgeon and think about (preventative) options that (they) might want to take,” Jackson explained. “So, I think this is a concern, that there's a group of people that are currently quite underserved and don't have the same access.”

Based on the study, the authors found that the BRCA1 and BRCA2 genes could cause an increased risk of breast cancer if an individual has an FDR with a history of breast cancer. They identified 230 women with pathogenic variant in the BRCA1 group and 611 women in the BRCA2 group, in which the women were placed into categories depending on whether they had an FDR with breast cancer.

Based on their analysis, the study authors found that women in the BRCA1 group who were age 60 and had a family history of breast cancer had a significantly higher chance of developing breast cancer, compared with the women in the BRCA1 group who were age 60 but did not have a family history of breast cancer.

Similarly, the study analyzed another type of pathogenic variant, Lynch syndrome, which is defined as “an inherited disorder that increases the risk of developing colorectal cancer… often before age 50. Lynch syndrome is caused by mutations (changes) in genes that affect DNA mismatch repair, a process that fixes mistakes that occur when DNA is copied,” according to National Cancer Institute. 

Lynch syndrome affects the genes including MLH1, MLH2 and MLH6. The study identified 89 patients with pathogenic variants in MLH1, 71 with MLH2 and 421 with MLH6. Individuals were placed into categories depending on potential family history with colorectal cancer.

The results in the analysis for Lynch syndrome were similar to the results for BRCA. The study authors found that individuals with an increased risk of developing Lynch syndrome were aged 60, had MLH1 and had an FDR with colorectal cancer.

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