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Genetic variants linked to male breast cancer found

A recent study published in the Journal of the National Cancer Institute has discovered three genetic variants linked to an increased risk of breast cancer in males.

Aetiology of male breast cancer

Male breast cancer is very rare, accounting for less than 1% of all breast cancer diagnoses. The aetiology for male breast cancer is poorly understood. In particular, how its genetic basis differs from female breast cancer. Family history and genetic susceptibility are considered important risk factors. Approximately 10% of cases are attributed to inherited BRCA2 mutations but only a small number of cases have BRCA1 mutations. This suggests differences in the underlying genetic aetiologies of male and female breast cancer.

Previous work, referenced in this study, revealed two predisposition loci for male breast cancer in a genome-wide association study (GWAS). These loci were also associated with risk of female breast cancer.

In this study, primarily funded by Breast Cancer Now, researchers performed genome-wide SNP genotyping. To do this, they used data from their previous GWAS alongside two additional case-control datasets. The aims of the research were to identify novel male breast cancer risk variants, to gain a better understanding of the genetic basis of the disease and to compare polygenic predispositions between male and female breast cancer.

Three novel genetic variants

The researchers identified three novel predisposition loci in male breast cancer that achieved genome-wide significance (P < 5 x 10-08). The variants – rs9371545, rs554219 and rs78540526 – increased the risk of developing male breast cancer by 47%, 45% and 61% respectively. Two variants mapped to 6q25.1 and one mapped to 11q13.3, making the total number of confirmed predisposition loci: five. These loci were also associated with risk of female breast cancer.

Due to differing frequencies of pathogenic variants in BRCA1 and BRCA2, it is often suggested that male and female breast cancer have distinct genetic aetiologies. However, this study provides evidence that there is actually a shared genetic basis for male and female (ER-positive) breast cancer.

Lead author, Dr Nick Orr, stated:

“Our findings suggest that the underlying biology that affects how breast cancer develops and grows are probably similar in men and women. This means that advances in prevention and treatment for the disease may be of benefit to all patients, irrespective of their gender.”

They also found from polygenic risk score analysis that males in the top quintile of genetic risk had a four-fold higher risk of breast cancer compared to males in the bottom quintile.

These findings provide further insight into the genetic basis of male breast cancer. It supports the idea that there is overlapping genetic aetiology with female breast cancer. This could impact future preventative treatments for both men and women. It also indicates that there is a group of susceptible men with a four-fold higher risk of developing male breast cancer.

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More on these topics

Cancer / Cancer Research / Genetic Variants

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