Cancer risk i...breast cancer_Jiaming Liu.pdf

Cancer Biol Med 2023.doi:10.20892/j.issn.2095-3941.2022.0593ORIGINAL ARTICLECancer risk in relatives of BRCA1/2 pathogenic variant carriers in a large series of unselected patients with breast cancerJiaming Liu,Lu Yao,Jie Sun,Li Hu,Jiuan Chen,Juan Zhang,Ye Xu,Yuntao XieKey Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Familial&Hereditary Cancer Center,Peking University Cancer Hospital&Institute,Beijing 100142,ChinaABSTRACT Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed.BRCA1/2 status was determined for all patients and relative risks(RRs)were calculated to evaluate cancer risk in relatives of the patients.Results:The incidences of breast cancer in female relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 33.0%,32.2%,and 7.7%,respectively.The corresponding incidences of ovarian cancer were 11.5%,2.4%,and 0.5%,respectively.The incidences of pancreatic cancer in male relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 1.4%,2.7%,and 0.6%,respectively.The corresponding incidences of prostate cancer were 1.0%,2.1%,and 0.4%,respectively.The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers(BRCA1:RR=4.29,P 0.001 and RR=21.95,P 0.001;BRCA2:RR=4.19,P 0.001 and RR=4.65,P 0.001,respectively).Additionally,higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers(RR=4.34,P=0.001 and RR=4.86,P=0.001,respectively).Conclusions:Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.KEYWORDS BRCA1 variant;BRCA2 variant;cancer risk in relatives;Chinese breast cancer patients;family history of cancerIntroductionGermline pathogenic variants in BRCA1/2 genes result in increased risks of various cancers via an autosomal dom-inant pattern of inheritance1.A series of studies on the spectrum and risk of cancer in BRCA1/2 pathogenic variant carriers(hereafter referred to BRCA1/2 carriers)have been conducted2-18.It is well-known that BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and BRCA2 carriers are at increased risk for pancreatic and prostate cancers2,6,7,9-11,16-18.The cancer risks and spectra appear to differ between BRCA1 and BRCA2 carriers;spe-cifically,the risk for ovarian cancer in BRCA1 carriers is higher than BRCA2 carriers2,7,17,and the risks for pancreatic and prostate cancers in BRCA2 carriers may be higher than BRCA1 carriers7,9-11,18.The associations between BRCA1/2 carriers and other cancers,such as colorectal and gastric cancers,have not been established,thus warrant further investigation3-6,11-15,17,18.Most previous studies involving BRCA-associated cancer have focused on BRCA1/2 carriers;however,a limited number of studies have examined the cancer risk and spectrum in rela-tives of BRCA1/2 carriers.One study reported that relatives of BRCA1 and BRCA2 carriers have an increased risk for breast and ovarian cancers,and relatives of BRCA2 carriers also have an increased risk for pancreatic cancer19.In addition,the data regarding the cancer risks in relatives of BRCA1/2 carriers are largely based on Western popula-tions;scant data exists that pertains to Chinese populations.Correspondence to:Yuntao XieE-mail:ORCID ID:https:/orcid.org/0000-0003-1151-8107Received September 27,2022;accepted December 19,2022Available at www.cancerbiomed.org2023 Cancer Biology&Medicine.Creative Commons Attribution-NonCommercial 4.0 International License148 Liu et al.Cancer risk in relatives of BRCA1/2 carriersChinese individuals have significantly different cancer spec-tra and risks compared with Western individuals,with rela-tively lower risks of breast and prostate cancers and relatively higher risks of gastric,esophageal,and liver cancers20,21.Moreover,the spectrum of BRCA1/2 variants in Chinese women is different from Western women,with approxi-mately 30%of variants not present in Caucasian women22-24.Therefore,the cancer risks in relatives of BRCA1/2 carriers in Chinese women might be different from Caucasian women.In the present study we aimed to clarify and characterize the spectra and risks of cancers in relatives of BRCA1/2 carriers in a large series of unselected Chinese patients with breast cancer.Materials and methodsStudy populationBetween October 2003 and May 2015,a total of 10,341 consec-utive patients with breast cancer who were treated at the Breast Center of Peking University Cancer Hospital&Institute were enrolled in a breast cancer database.All patients were con-firmed to have breast cancer based on preoperative biopsy or postoperative h