The role of BRCA genes in repairing DNA double strand breaks by homologous recombination is well established [9]. BRCA variants contribute to the development of many cancers [10]. The cancers most associated with BRCA mutation are breast and ovarian cancer [11]. Germline variants in BRCA genes show increased lifetime risk up to 85% for breast cancer and 40% for ovarian cancer [11, 12]. Also, BRCA variants are associated with prostate, melanoma, pancreas, and stomach cancer [13, 14]. However, studies investigating the relationship between BRCA and development of CRCs have showed conflicting results [3–8].
Recently, studies investigating the effects of germline variations in the BRCA gene on the occurrence of cancers other than breast and ovarian cancers are being actively conducted [14, 15, 21, 22]. Some reports indicated that colorectal cancer was significantly elevated for BRCA1 carriers [15]. However, there have been other studies showing that BRCA1 mutations do not affect the development of CRC [5, 7, 8]. Additionally, many of the studies regarding the development of CRCs association with BRCA mutations, are based on evaluating women, especially women with history of breast or ovarian cancer harboring germline BRCA mutation [3,14,15,23–25]. There is relatively little interest in men with the BRCA cancer family, and this may be related to the possibility of delayed early detection of cancer in male patients.
In a previous study, the risk of early-onset colorectal cancer was significantly increased in BRCA1 carriers and the cutoff used was < 50 years of age [3]. In a report related to surveillance on male BRCA carriers, it was suggested that cancer monitoring in male BRCA mutation carriers should be started at the age of 40 [16]. A recent case report of a patient with early-onset CRC with a germline BRCA1 mutation was a 33-year-old man [17]. In our case, the patient was 39 years old. When CRC develops in young patients, efforts are needed to differentiate it from hereditary disease. Although BRCA mutations are not frequent, it may be necessary to investigate the possibility of BRCA-associated CRC in cases other than Lynch syndrome, familial adenomatous polyposis, or MUTYH-associated polyposis.
Alteration of BRCA genes are known substantially contribute to the development of prostate cancer [18]. Recent study showed that the among the 620 prostate cancer patients, 6.4% had germline BRCA variation [19]. Family history is one of the important risk factors for having prostate cancer. Therefore, our patients may have higher risk of prostate cancer than other BRCA-associated cancers. Regular screening for prostate cancer through serum PSA level test was recommended.
BRCA-mutated cancers are sensitive to platinum-based therapy [20].The effectiveness of platinum-based therapy in BRCA mutated cancers are well studied in breast and ovarian cancer [21, 22]. Although, studies are limited in BRCA-mutated CRCs, in the previous report of a rectal cancer patient with germline BRCA1 variant, the patient showed complete response to neoadjuvant chemoradiation, and a platinum-based agent was included in chemotherapeutic regimen [17]. We added the platinum agent in the regimen for neoadjuvant therapy based on the detection of the germline BRCA1 variant and hypothesized that adding platinum agent might be responsible for excellent response [17]. Our patient showed moderate response (AJCC tumor regression grade system) after standard neoadjuvant chemoradiation, which the regimen included receiving radiation (5040 cGy) with capecitabine. We did not add a platinum agent in the neoadjuvant therapy regimen because the genetic status of the rectal cancer was not available at that time. After the surgery, the patient received eight cycles of 5-FU- and oxaliplatin-based chemotherapy. The patient showed complete response and is alive without recurrence or metastasis. The platinum agent included in the adjuvant chemotherapy was oxaliplatin and we suspected that the germline BRCA1 variant might have contributed to the good response.
In conclusion, we presented a case of CRC in a young-aged patient with a germline BRCA1 variant. Although our observation has limitations because it is a single case report, our case reports implicate that the testing for detection of germline BRCA mutations should be considered in young-aged CRC patients, especially in patients that have family history of cancer. The accumulation of male BRCA-related CRC reports may contribute to establishing a relationship between the two.