Study identifies genes predisposing to breast cancer among women with localized breast cancer

Identification of a number of cancer predisposition genes can help improve risk assessment and counseling for ductal carcinoma in situ and contralateral breast cancer.

Disease-causing genetic variants in a number of cancer predisposition genes have been identified as carrying a moderate or high risk of developing ductal carcinoma in situ (DCIS) or breast ductal carcinoma in situ (IDBC) for women. The data was presented at the 2022 American Association for Cancer Research Special Conference, Rethinking DCIS: An Opportunity for Prevention?1

The study authors, led by Huaizhi (Gilbert) Huang, BS, a graduate student at the Mayo Clinic in Rochester, Minnesota, aimed to estimate women’s risk of DCIS and breast cancer among germline mutation carriers, as well as the association between DCIS and breast cancer carriers. BRCA1/2 Not well established.

The researchers looked at 11 cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, RAD51CAnd the RAD51D) for any association between disease-causing genetic variants and DCIS. They analyzed it using a case control group of 3876 women with ductal carcinoma in situ and age-matched women who did not have ductal carcinoma in situ from a population study; 9,887 women with DCIS underwent genetic testing at Ambry Genetics between March 15, 2012 and December 30, 2016; and an unaffected control group from the genome assembly database.

In the set of clinical tests, pathogenic variants were observed in 7 cancer predisposition genes and were associated with an increased risk of ductal carcinoma in situ, reaching an odds ratio greater than 2. CDH1 And the BRCA2 Genes, in particular, were associated with an OR higher than 4.

Four cancer susceptibility genes were highlighted in the population: BRCA1, CHEK2, PALB2And the ATM.

We found that disease-causing variants in 4 genes predispose to cancer BRCA1, CHEK2, PALB2And the ATMIn a poster presentation at the conference, Huang said:

In both groups, pathogenic variants in BRCA1, BRCA2And the PALB2 were associated with an increased incidence of ductal carcinoma in situ via IDBC (s <.05). Among patients with ductal carcinoma in situ who were carriers of pathogenic variants in these genes, the incidence of contralateral breast cancer was 11% at 5 years and 20% at 15 years.

The frequencies of cancer predisposition mutations in DCIS and IDBC cases from the clinical test suite are included in the table. The frequencies were lower in the population-based group and the odds ratios were higher.

In both groups, the frequencies of pathogenic variants in ATM And the CHEK2 Genes were similar for women with DCIS and women with IDBC. Huang et al suggested that genetic testing for these genes could be used for women with ductal carcinoma in situ.

There were fewer cases of pathogenic variants in BRCA1, BRCA2, And the PALB2 Genes for women with ductal carcinoma in situ compared to those with IDBC but these variants are still associated with a higher risk of ductal carcinoma in situ. As such, the study authors recommended that contralateral prophylactic mastectomy may be considered in women with ductal carcinoma in situ who carry disease-causing gene variants in their BRCA1, BRCA2wow PALB2.

They noted that identifying cancer predisposition genes could help improve risk assessment and counseling for DCIS and contralateral breast cancer.

reference
1. Huang H, Couch RE, LaDuca H, et al. Risk of ductal carcinoma in situ of the breast associated with disease-causing variants in cancer predisposition genes. Poster Presented at: The 2022 AACR Special Conference Rethinking DCIS: An Opportunity for Prevention? 8-11 September 2022; Philadelphia, Pennsylvania. Abstract A003.

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