Today, I review, link to, and excerpt from “First-degree family history of prostate cancer is associated the risk of breast cancer and ovarian cancer”. Medicine (Baltimore). 2021 Jan 29;100(4):e23816. doi: 10.1097/MD.0000000000023816. [PubMed Abstract] [Full-Text HTML] [Full-Text PDF].
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It is worth reviewing the entire article. However, based on my reading of the entire article, I don’t see any actionable strategies for risk reduction of breast and ovarian cancer in first degree relatives of patients with prostate cancer.
It is also not clear to me that the study demonstrates clinically meaningful increased riskof ovarian and breast cancer in patients with first degree relatives of patients with prostate cancer.
However, if the physician or patient is concerned about the possiblity of increased risk of ovarian or breast cancer because of a first degree relative with prostate cancer, referral to a medical geneticist may be indicated.
In the article, the authors state:
However, some limitations of the present study should be considered.
Firstly, there were too few studies to draw a solid conclusion for the risk of ovarian cancer in people with family history of prostate cancer, more prospective cohort studies are still needed to evaluate the risk of ovarian cancer in people with family history of prostate cancer. [Emphasis Added]
Second, we didn’t estimate the association between history of prostate cancer among parent or sibling and risk of breast cancer due to the lack of information available in the original studies. [Emphasis added]
All that follows is from “First-degree family history of prostate cancer is associated the risk of breast cancer and ovarian cancer”.
Abstract
The evidence for associations between family history of prostate cancer and the risk of breast cancer and ovarian cancer is
inconclusive. The first systematic review and meta-analysis of studies was conducted to assess the risk of breast cancer and ovarian cancer associated with a family history of prostate cancer.A literature search was conducted using MEDLINE, Embase and Web of science databases up to January 31, 2019. Data were
screened and extracted independently by 2 reviewers. The pooled risk ratio (RR) and its 95% confidence interval (CI) were calculated using random-effects models. The GRADE approach was used to assess the quality of evidence.Nine observational studies including 8,011,625 individuals were included in the meta-analysis. The meta-analysis showed that
family history of prostate cancer in first-degree relatives was associated with an increased risk of breast cancer (RR 1.12, 95%CI 1.09 to 1.14) with moderate quality evidence, subgroup analysis showed consistent results. Compared with no family history of prostate cancer, history of prostate cancer in first-degree relatives was associated with a slight risk of ovarian cancer (1.10, 95%CI 1.01 to 1.20) with moderate quality evidence. Family history of prostate cancer among sibling was associated with a 17% increased risk of ovarian cancer (95% CI 1.03 to 1.34), however, no significant association was found between family history of prostate cancer among parent and risk of ovarian cancer (RR 1.19, 95% CI 0.84 to 1.70).This review demonstrates that women with a family history of prostate cancer in first-degree relatives was associated with an
increased risk of breast cancer and ovarian cancer. These findings may aid in screening, earlier detection and treatment of women with a family history of prostate cancer in first-degree relatives.Abbreviations: BRCA = breast cancer susceptibility gene, CI = confidence interval, HRs = hazard ratios, ORs = odds ratios, RR
= risk ratio.Keywords: breast cancer, family history, meta-analysis, ovarian cancer, prostate cancer
1. Introduction
Breast cancer is the most common cancer worldwide in women.[1] Cancer epidemiological data showed that an estimated about 2,088,849 new breast cancer cases and almost 626,679 cancer deaths worldwide in 2018.[2] Meanwhile, about 295,414 new ovarian cancer cases and almost 184,799 cancer deaths worldwide in 2018.[2] Ovarian cancer is less common, but is associated with much high mortality.[3,4] Family history is a well-established risk factor for both cancers.[5,6] Compared to the women without a first-degree relative with breast cancer, those with a family history of breast cancer in first-degree relatives had a 2.1 times greater risk of developing breast cancer.[7] Women with a family history of ovarian cancer in first-degree relatives had a 3.1 times greater risk of developing ovarian cancer.[8]
It is estimated that approximately 5% to 10% of all breast cancer cases and 10% to 15% of all ovarian cancers are thought to be hereditary.[9–11] Hereditary breast and ovarian cancer syndrome have been considered to be associated with deleterious mutations in the breast cancer susceptibility gene (BRCA) genes.[12,13] Previous studies have reported that individuals with mutations in BRCA1 and BRCA2 are at an increased risk of developing breast, ovarian, prostate and other cancers.[13,14] The lifetime risk of breast cancer in BRCA1 and BRCA2 mutation carriers is 45–80% and for ovarian cancer, the lifetime risk is 45% to 60%.[15] In addition, germline mutations in the BRCA2 gene confer an 8.6-fold increased risk of prostate cancer and BRCA1 mutation carriers have a 3.8-times increased risk of prostate cancer in men younger than 65 years.[14,16] The BRCA gene alteration may be responsible for the clustering of breast, ovarian and prostate cancer.
Moreover, previous observational studies have reported family history of prostate cancer may be associated with risk of breast cancer and ovarian cancer. However, the results from these studies remain controversial. Therefore, to help clarify the evidence, we performed a systematic review and meta-analysis of all studies investigating the associations of family history of prostate cancer with breast cancer and ovarian cancer risk.
3.2. Associations between family history of prostate cancer and the risk of breast cancer incidence
Seven studies with 8,008,342 individuals in total evaluated the association between family history of prostate cancer and the risk of breast cancer incidence. The history of prostate cancer in first-degree relatives was significantly associated with breast cancer risk (RR = 1.12, 95% CI = 1.09–1.14, I2 = 0.00%) (Fig. (Fig.2),2), with moderate quality evidence (Table (Table1).1). This increased risk with family history of prostate cancer persisted in subgroup analysis based on study design (cohort study: RR, 1.11; 95% CI, 1.09–1.14, I2 = 0.00%, case-control study: RR, 1.12; 95% CI, 1.05–1.40, I2 = 17.50%) and study region (Europe: RR, 1.11; 95% CI, 1.08–1.14, I2 = 0.00%, America: RR, 1.16; 95% CI, 1.07–1.25, I2 = 0.00%, Asia: RR, 1.70; 95% CI, 1.15–2.50) (Table (Table44).
3.3. Associations between family history of prostate cancer and the risk of ovarian cancer incidence
Four studies with 7,850,244 individuals in total evaluated the association between family history of prostate cancer and the risk of ovarian cancer incidence. The history of prostate cancer in first-degree relatives was slightly associated with ovarian cancer risk (RR = 1.10, 95% CI = 1.01–1.20, I2 = 11.30%) (Fig. (Fig.3),3), with moderate quality evidence (Table (Table4).4). When we stratified our analysis by study design, there was no statistically significant increased association in the 2 pooled cohort studies (RR, 1.09; 95% CI, 0.99–1.21; I2 = 46.40%) and in the 2 pooled case-control studies (RR = 1.33, 95% CI = 0.89–1.98, I2 = 0.00%) (Table (Table4).4). Subgroup analyses based on study region showed that a slightly significant increased association between history of prostate cancer and ovarian cancer risk was observed in Europe (RR = 1.08, 95% CI = 1.01–1.16, I2 = 0.00%), but not in America (RR = 1.64, 95% CI = 0.97–2.76) and Asia region (RR = 0.60, 95% CI = 0.03–10.73) (Table (Table4).4). In addition, subgroup analyses based on source of history showed that family history of prostate cancer among sibling was associated with ovarian cancer risk (RR = 1.17, 95% CI = 1.03–1.34), however, no association was found between family history of prostate cancer among parent and ovarian cancer risk (RR = 1.19, 95% CI = 0.84–1.70) (Table (Table44).
4. Discussion
Nine studies with a total of 8,011,625 participants met the inclusion criteria and were finally included into the meta-analysis. The findings of this meta-analysis suggest that the risk of breast cancer and ovarian cancer was increased in people with family history of prostate cancer in first relatives. In addition, we also found that increased ovarian cancer risk in people with family history of prostate cancer among sibling, but not among parent. These findings may assist in targeting screening, earlier detection and treatment of breast cancer and ovarian cancer.
The cancer pathogenesis include both heritable and environmental causation.[27] Family history was one of the most significant risk factors for breast cancer and ovarian cancer.[7,8] A family history of prostate cancer has also been reported as a possible risk factor for breast cancer and ovarian cancer.[24]
In our analysis, we observed an increased risk of breast cancer and ovarian cancer in women with a family history of prostate cancer. Subgroup meta-analyses based on study design and study region showed the consistent results for breast cancer risk. However, no significant association was observed between family history of prostate cancer and ovarian cancer risk in the pooled cohort studies and the pooled case-control studies.
The underlying mechanisms of the associations are still unclear. A common gene alteration may be responsible for the clustering of prostate, breast cancer and ovarian cancer.[28] The BRCA1 and BRCA2 genes mutation, confirmed to be linked with breast cancer, ovarian cancer and prostate cancer.[14,28] The BRCA1 and BRCA2 genes mutation confer a 3.8-and 8.6-fold increased risk of developing prostate cancer, respectively.[14,16] Further, previous study reported that 55% to 65% of women with a deleterious BRCA1 mutation and approximately 45% of women with a deleterious BRCA2 mutation will develop breast cancer by age 70 years.[29] In addition, about 39% of women who inherit a harmful BRCA1 mutation and 11% to 17% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years.[30] These mutations could therefore be responsible for part of the identified associations between family history of prostate cancer and breast cancer and ovarian cancer risk. Further studies are needed to explore the mechanism of the association between family history of prostate cancer and risk of breast and ovarian cancer, and provide further data on the incidence and prognosis of breast and ovarian cancer in women with family history of prostate cancer.
To our knowledge, this is the first meta-analysis that evaluates the association between family history of prostate cancer and breast cancer and ovarian cancer risk. The sample size in our study is the large. There is no significant heterogeneity and publication bias in our meta-analysis. In addition, the quality of evidence for the main outcome was assessed rigorously using GRADE approach.
However, some limitations of the present study should be considered.
Firstly, there were too few studies to draw a solid conclusion for the risk of ovarian cancer in people with family history of prostate cancer, more prospective cohort studies are still needed to evaluate the risk of ovarian cancer in people with family history of prostate cancer. [Emphasis Added]
Second, we didn’t estimate the association between history of prostate cancer among parent or sibling and risk of breast cancer due to the lack of information available in the original studies. [Emphasis added]
Thirdly, although no remarkable publication bias was observed based on the funnel plot, Begg test and Egger test, some publication bias may exist in the results because only studies published in English language were included.
5. Conclusion
In conclusion, results of this meta-analysis indicate that family history of prostate cancer in first relatives was associated with an increased risk of breast cancer and ovarian cancer. The findings may assist in targeting screening, earlier detection and treatment of breast cancer and ovarian cancer. However, further prospective cohort studies are needed to provide more conclusive evidence.
It is worth reviewing the entire article. However, based on my reading of the entire article, I don’t see any actionable strategies for risk reduction of breast and ovarian cancer in first degree relatives of patients with prostate cancer.
It is also not clear to me that the study demonstrates clinically meaningful increased riskof ovarian and breast cancer in patients with first degree relatives of patients with prostate cancer.
However, if the physician or patient is concerned about the possiblity of increased risk of ovarian or breast cancer because of a first degree relative with prostate cancer, referral to a medical geneticist may be indicated.
