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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Research

BRCA genes as candidates for colorectal cancer genetic testing panel: systematic review and meta-analysis

Authors: Zhewen Feng, Xiaobao Yang, Mingwei Tian, Na Zeng, Zhigang Bai, Wei Deng, Yanyan Zhao, Jianru Guo, Yingchi Yang, Zhongtao Zhang, Yun Yang

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Breast cancer susceptibility gene (BRCA) mutation carriers are at an increased risk for breast, ovarian, prostate and pancreatic cancers. However, the role of BRCA is unclear in colorectal cancer; the results regarding the association between BRCA gene mutations and colorectal cancer risk are inconsistent and even controversial. This study aimed to investigate whether BRCA1 and BRCA2 gene mutations are associated with colorectal cancer risk.

Methods

In this systematic review, we searched PubMed/MEDLINE, Embase and Cochrane Library databases, adhering to PRISMA guidelines. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Unadjusted odds ratios (ORs) were used to estimate the probability of Breast Cancer Type 1 Susceptibility gene (BRCA1) and Breast Cancer Type 2 Susceptibility gene (BRCA2) mutations in colorectal cancer patients. The associations were evaluated using fixed effect models.

Results

Fourteen studies were included in the systematic review. Twelve studies, including seven case–control and five cohort studies, were included in the meta-analysis. A significant increase in the frequency of BRCA1 and BRCA2 mutations was observed in patients with colorectal cancer [OR = 1.34, 95% confidence interval (CI) = 1.02–1.76, P = 0.04]. In subgroup analysis, colorectal cancer patients had an increased odds of BRCA1 (OR = 1.48, 95% CI = 1.10–2.01, P = 0.01) and BRCA2 (OR = 1.56, 95% CI = 1.06–2.30, P = 0.02) mutations.

Conclusions

BRCA genes are one of the genes that may increase the risk of developing colorectal cancer. Thus, BRCA genes could be potential candidates that may be included in the colorectal cancer genetic testing panel.
Appendix
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Literature
1.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.CrossRefPubMed
2.
Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64.CrossRefPubMed
3.
Ballester V, Rashtak S, Boardman L. Clinical and molecular features of young-onset colorectal cancer. World J Gastroenterol. 2016;22(5):1736–44.PubMedPubMedCentral
4.
Weinberg BA, Marshall JL, Salem ME. The growing challenge of young adults with colorectal cancer. Oncology (Williston Park). 2017;31(5):381–9.PubMed
5.
Hall JM, Lee MK, Newman B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990;250(4988):1684–9.PubMed
6.
Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994;265(5181):2088–90.PubMed
7.
Venkitaraman AR. Cancer suppression by the chromosome custodians, BRCA1 and BRCA2. Science. 2014;343(6178):1470–5.PubMed
8.
Filipponi D, Muller J, Emelyanov A, Bulavin DV. Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA methylation. Cancer Cell. 2013;24(4):528–41.PubMed
9.
Savage KI, Gorski JJ, Barros EM, et al. Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability. Mol Cell. 2014;54(3):445–59.PubMedPubMedCentral
10.
Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117–30.PubMedPubMedCentral
11.
Chen S, Iversen ES, Friebel T, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006;24(6):863–71.PubMed
12.
Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4(9):665–76.PubMed
13.
Lee YC, Lee YL, Li CY. BRCA genes and related cancers: a meta-analysis from epidemiological cohort studies. Medicina (Kaunas). 2021;57(9):905.
14.
Nyberg T, Frost D, Barrowdale D, et al. Prostate cancer risks for male BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Eur Urol. 2020;77(1):24–35.PubMedPubMedCentral
15.
Hu C, Hart SN, Polley EC, et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA. 2018;319(23):2401–9.PubMedPubMedCentral
16.
Phelan CM, Iqbal J, Lynch HT, et al. Incidence of colorectal cancer in BRCA1 and BRCA2 mutation carriers: results from a follow-up study. Br J Cancer. 2014;110(2):530–4.PubMed
17.
Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 1999;91(15):1310–6.
18.
Garcia-Patiño E, Gomendio B, Provencio M, et al. Germ-line BRCA1 mutations in women with sporadic breast cancer: clinical correlations. J Clin Oncol. 1998;16(1):115–20.PubMed
19.
Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994;343(8899):692–5.PubMed
20.
Fujita M, Liu X, Iwasaki Y, et al. Population-based Screening for Hereditary Colorectal Cancer Variants in Japan. Clin Gastroenterol Hepatol. 2022;20(9):2132-2141.e9.
21.
Cullinane CM, Creavin B, O’Connell EP, et al. Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: systematic review and meta-analysis. Br J Surg. 2020;107(8):951–9.PubMed
22.
Oh M, McBride A, Yun S, et al. BRCA1 and BRCA2 gene mutations and colorectal cancer risk: systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(11):1178–89.PubMed
23.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.PubMedPubMedCentral
24.
Akcay IM, Celik E, Agaoglu NB, et al. Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls. Int J Cancer. 2021;148(2):285–95.PubMed
25.
Chen-Shtoyerman R, Figer A, Fidder HH, et al. The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients. Br J Cancer. 2001;84(4):475–7.PubMedPubMedCentral
26.
Dobbins SE, Broderick P, Chubb D, Kinnersley B, Sherborne AL, Houlston RS. Undefined familial colorectal cancer and the role of pleiotropism in cancer susceptibility genes. Fam Cancer. 2016;15(4):593–9.PubMedPubMedCentral
27.
Kadouri L, Hubert A, Rotenberg Y, et al. Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations. J Med Genet. 2007;44(7):467–71.PubMedPubMedCentral
28.
Kirchhoff T, Satagopan JM, Kauff ND, et al. Frequency of BRCA1 and BRCA2 mutations in unselected Ashkenazi Jewish patients with colorectal cancer. J Natl Cancer Inst. 2004;96(1):68–70.PubMed
29.
Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121(2):269–75.PubMed
30.
Niell BL, Rennert G, Bonner JD, Almog R, Tomsho LP, Gruber SB. BRCA1 and BRCA2 founder mutations and the risk of colorectal cancer. J Natl Cancer Inst. 2004;96(1):15–21.PubMed
31.
Suchy J, Cybulski C, Górski B, et al. BRCA1 mutations and colorectal cancer in Poland. Fam Cancer. 2010;9(4):541–4.PubMed
32.
Thompson D, Easton DF, Breast Cancer Linkage Consortium. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94(18):1358–65.PubMed
33.
Yurgelun MB, Kulke MH, Fuchs CS, et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol. 2017;35(10):1086–95.PubMedPubMedCentral
34.
Deng CX, Brodie SG. Roles of BRCA1 and its interacting proteins. BioEssays. 2000;22(8):728–37.PubMed
35.
Huen MS, Sy SM, Chen J. BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol. 2010;11(2):138–48.PubMed
36.
Moynahan ME, Pierce AJ, Jasin M. BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell. 2001;7(2):263–72.PubMed
37.
Godet I, Gilkes DM. BRCA1 and BRCA2 mutations and treatment strategies for breast cancer. Integr Cancer Sci Ther. 2017;4(1):10.15761/ICST.1000228.
38.
Winter C, Nilsson MP, Olsson E, et al. Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic. Ann Oncol. 2016;27(8):1532–8.PubMedPubMedCentral
39.
Caulfield SE, Davis CC, Byers KF. Olaparib: a novel therapy for metastatic breast cancer in patients with a BRCA1/2 mutation. J Adv Pract Oncol. 2019;10(2):167–74.PubMedPubMedCentral
40.
41.
42.
Mittica G, Ghisoni E, Giannone G, et al. PARP inhibitors in ovarian cancer. Recent Pat Anticancer Drug Discov. 2018;13(4):392–410.PubMed
43.
Cortesi L, Rugo HS, Jackisch C. An overview of PARP inhibitors for the treatment of breast cancer. Target Oncol. 2021;16(3):255–82.PubMedPubMedCentral
44.
Shao F, Duan Y, Zhao Y, et al. PARP inhibitors in breast and ovarian cancer with BRCA mutations: a meta-analysis of survival. Aging (Albany NY). 2021;13(6):8975–88.PubMed
45.
Pilié PG, Gay CM, Byers LA, O’Connor MJ, Yap TA. PARP inhibitors: extending benefit beyond BRCA-mutant cancers. Clin Cancer Res. 2019;25(13):3759–71.PubMed
46.
Pant S, Maitra A, Yap TA. PARP inhibition - opportunities in pancreatic cancer. Nat Rev Clin Oncol. 2019;16(10):595–6.PubMed
47.
Mateo J, Lord CJ, Serra V, et al. A decade of clinical development of PARP inhibitors in perspective. Ann Oncol. 2019;30(9):1437–47.PubMedPubMedCentral
48.
Yang Y, You YN. ASO author reflections: toward molecularly-driven personalized care for young adults with rectal cancer. Ann Surg Oncol. 2019;26(Suppl 3):656–7.PubMed
49.
Copson ER, Maishman TC, Tapper WJ, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018;19(2):169–80.PubMedPubMedCentral
50.
Mardis ER. DNA sequencing technologies: 2006–2016. Nat Protoc. 2017;12(2):213–8.PubMed
51.
Levy SE, Myers RM. Advancements in next-generation sequencing. Annu Rev Genomics Hum Genet. 2016;17:95–115.PubMed
52.
Liu Q, Fang L, Yu G, Wang D, Xiao CL, Wang K. Detection of DNA base modifications by deep recurrent neural network on Oxford Nanopore sequencing data. Nat Commun. 2019;10(1):2449.PubMedPubMedCentral
53.
David M, Dursi LJ, Yao D, Boutros PC, Simpson JT. Nanocall: an open source basecaller for Oxford Nanopore sequencing data. Bioinformatics. 2017;33(1):49–55.PubMed
Metadata
Title
BRCA genes as candidates for colorectal cancer genetic testing panel: systematic review and meta-analysis
Authors
Zhewen Feng
Xiaobao Yang
Mingwei Tian
Na Zeng
Zhigang Bai
Wei Deng
Yanyan Zhao
Jianru Guo
Yingchi Yang
Zhongtao Zhang
Yun Yang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11328-w

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