Analysis of polymorphisms in genes associated with the FA/BRCA pathway in three patients with multiple primary malignant neoplasms

Abstract

Cases of more than three primary cancers are very rare. This study analyzed the genetic susceptibility of gene polymorphisms in three patients with multiple primary malignant neoplasms and examined the possible pathogenesis. The clinical data and whole genome sequence of three patients (1 with 5 primary cancers, 1 with 4 primary cancers, and 1 with 3 primary cancers) were aligned with a series of databases. We found the three patients contained a total of seven types of malignant tumours (endometrial cancer, ovarian cancer, breast cancer, colon cancer, ureter cancer, bladder cancer and kidney cancer). It was found that the varied genes in Patient 1 (5 primary cancers) were BRIP1, FANCG, NBN, AXIN2, SRD5A2, and CEBPA. Patient 2 (4 primary cancers) had variations in the following genes: BMPR1A, FANCD2, MLH3, BRCA2, and FANCM. Patient 3 (3 primary cancers) had variations in the following genes: MEN1, ATM, MSH3, BRCA1, FANCL, CEBPA, and FANCA. String software was used to analyze the KEGG pathway of the variations in these three samples, which revealed that the genes are involved in the Fanconi anaemia pathway. Defects in DNA damage repair may be one of the causes of multiple primary cancers.

Keywords:

• Multiple primary malignant neoplasms
• gene polymorphisms
• second-generation whole-genome sequencing technology
• FA/BRCA pathway
• DNA damage repair

Acknowledgements

The authors thank Zheling Chen and Yisong Xu for excellent technical assistance.

Disclosure statement

The authors report no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Data availability

All data generated or analysed during this study are included in this published article

Additional information

Funding

This work was supported by the [Fundamental Research Funds of the First Affiliated Hospital of XI'an Jiao Tong University] under Grant [number 2017QN-08]. Ethical approval number:XJTU1AF2017LSK-132.