In terms of the risks of other primary cancers, Ford et al. [
1] showed the risks of not only breast and ovarian cancer, but also other cancers in
BRCA1 gene mutation carriers. The estimated cumulative risk of breast cancer in gene carriers is 87% by age 70. Primary ovarian cancers occur in women with previous breast cancer, resulting in an estimated cumulative risk of ovarian cancer of 44% by age 70. Based on national incidence rates, significant excesses were observed for colon cancer (estimated relative risk (RR) to gene carriers 4.11 [95% confidence interval (CI) 2.36–7.15]) and prostate cancer (3.33 [1.78–6.20]); no significant excesses were noted for cancers of other sites. This study showed that carriers have increased risks for colon and prostate cancer, which provides clinical significance in certain family members if the risks are associated with particular mutations. Thompson et al. [
3] conducted a cohort study to evaluate the risks of other cancers in
BRCA1 gene mutation carriers.
BRCA1 gene mutation carriers were found to have a statistically significant increase in risk for several cancers, including pancreatic cancer (RR = 2.26, 95% CI = 1.26 to 4.06,
p = 0.004) and cancer of the uterine body and cervix (uterine body RR = 2.65, 95% CI = 1.69 to 4.16,
p < 0.001; cervix RR = 3.72, 95% CI = 2.26 to 6.10,
p < 0.001). There was some evidence of an elevated risk of prostate cancer in mutation carriers younger than 65 years old (RR = 1.82, 95% CI = 1.01 to 3.29,
p = 0.05), but not in those 65 years old or older (RR = 0.84, 95% CI = 0.53 to 1.33,
p = 0.45). Similarly, Easton et al. [
21] showed the risks of certain cancers in
BRCA2 gene mutation carriers. Statistically significant increases in risks were observed for prostate cancer (estimated RR = 4.65; 95% CI = 3.48–6.22), pancreatic cancer (RR = 3.51; 95% CI = 1.87–6.58), gallbladder and bile duct cancer (RR = 4.97; 95% CI = 1.50–16.52), stomach cancer (RR = 2.59; 95% CI = 1.46–4.61), and malignant melanoma (RR = 2.58; 95% CI = 1.28–5.17). Friedenson et al. [
4] evaluated the
BRCA1 gene and
BRCA2 gene pathways and the risk of cancers other than breast or ovarian. Although these mutations target the breast and ovary, a broader spectrum of cancers also occur with statistically significant elevated frequencies. Additional sites at risk include the stomach, pancreas, prostate, and colon. The increased risk ranged from about 20 to 60%, with the greatest risk increases occurring in the stomach and pancreas. In this background, Shih et al. [
6] evaluated the incidence of BRCA mutations in breast cancer families with multiple primary cancers. Ninety-eight women selected from high-risk breast/ovarian cancer clinics with breast cancer reporting at least one other primary cancer in themselves or in a relative with breast cancer were compared to 99 women with breast cancer who reported a family history of breast cancer only. They concluded that the presence of multiple primary cancers predicted an increased likelihood of finding either a
BRCA1 or
BRCA2 gene mutation.
In this current study, we confirmed that BRCA mutation was detected more prevalently in families with histories of other primary cancers than those without any history of other primary cancers (22.7% vs. 11.7%, p < 0.001). Binary logistic regression analysis supported this finding that BRCA mutations was significantly associated with the occurrence of other primary cancers in families of high-risk patients (p < 0.001). A younger age at diagnosis (p = 0.044) and bilateral breast cancer (p = 0.006) were also associated with the occurrence of other primary cancers in families of high-risk patients. The most prevalent other primary cancer was stomach cancer, which was more common in South Korea than anywhere else in the world. In the BRCA-positive group, the proportional incidence of stomach cancer was 13.8%, which was relatively higher than that in the BRCA-negative group (7.4%, p = 0.003). Similar to previous studies, the risk of pancreatic cancer was higher among carriers of a BRCA mutation. BRCA mutations were also shown to be predisposing factors for the development of colorectal cancer, lung cancer, and uterine cancer in this study. Specifically, in the BRCA-positive group, the proportional incidences of pancreas, colorectal, lung, and uterine cancer were 4.0, 7.7, 8.8, and 5.0%, respectively; these were relatively higher than those in the BRCA-negative group. Not only environmental and genetic factors, but also cancer susceptibility from the BRCA mutation may contribute to the distribution of familial cancer. Our current study has a limitation: although the familial pedigree was organized thoroughly by a research nurse, the occurrence of other primary cancers in first- and second-degree relatives of high-risk patients could have been under-estimated due to a lack of information. Nonetheless, our current study supports previous studies suggesting that BRCA1 gene and BRCA2 gene mutations may be associated with increased susceptibilities to cancers other than breast and ovarian cancer. In addition to the large risks of breast and ovarian cancers, BRCA mutations may be associated with increased risks of several other cancers, particularly stomach, uterine, and pancreatic cancers.