Selenium and the risk of cancer in BRCA1 carriers

Abstract

It has not been established if dietary factors or nutritional supplements impact on the incidence of cancer in high-risk women. We randomised 1135 women with a BRCA1 mutation to 250 micrograms daily of elemental selenium as sodium selenite, or to placebo, in a double-blind trial. After a median follow-up period of 35 months (range 6 to 62 months), there were 60 incident cases of cancer diagnosed in the selenium-supplemented group, versus 45 cases in the placebo group (hazard ratio 1.4; 95% CI: 0.9 to 2.0). Selenium supplementation was not associated with a reduction in the risk of primary breast cancer (hazard ratio 1.3; 95% CI: 0.7 to 2.5), of contralateral breast cancer (hazard ratio 1.5; 95% CI: 0.7 to 3.2), or of ovarian cancer (hazard ratio 1.3; 95% CI: 0.6 to 2.7). The results of this study do not support the recommendation that selenium supplementation should be offered to BRCA1 carriers for chemoprevention.Part II Adnexectomy, genotypes and selenium level as markers of the risk of cancer In these part we conducted a nested case-control study of 68 women with breast cancer and 17 women with ovarian cancer and 170 controls matched 1 to 2. Cases and controls were matched for age at enrolment, past history of breast cancer, oophorectomy and whether they received selenium supplement or placebo during cancer chemoprevention trial. Combinations of clinical status, genotypes and selenium levels strongly associated with extremely low risk of cancer have been identified.The strongest associations have been found for GPX4 variants:a. all nTT and Se level 60-80µg/l -OR 0.32, p: 0.0009 b. all TT and Se level >80µg/l -OR 0.10, p: 0.047 c. for carriers without adnexectomy and with TT variant, Se level >80µg/l -OR 0.038, p: 0.014.

Health risk assessment of environmental selenium: Emerging evidence and challenges

“…Overall, all the recent trials have consistently shown that selenium does not modify risk of overall cancer, prostate cancer and other specific cancers ( 2 , 3 , 23 , 43 – 45 ), while it may even increase risk of cancers such as advanced ( 46 , 47 ) or overall prostate cancer ( 48 ), non-melanoma skin cancer ( 49 , 50 ) and possibly breast cancer in high-risk women ( 51 ). These results strongly and unexpectedly differ from the results reported in the earliest trial, the NPC ( 49 , 52 ), which however was small and more importantly was later found to be affected by a detection bias ( 53 ).…”

Selenium and Health: An Update on the Situation in the Middle East and North Africa

“…Moreover, three recent RCTs evaluated Se impact on participants with high risk for prostate cancer and all showed no beneficial effect of Se on the incidence of cancer [36,37,38]. Additionally, a trial among women with high risk of breast cancer due to mutations to breast cancer type 1 (BRCA1) susceptibility gene showed increased risk of all cancers and primary breast cancer in Se-supplemented arm compared to placebo [39]. Observational studies have also assessed Se effect on cancer risk with strongly conflicting results.…”

Friend or Foe? The Current Epidemiologic Evidence on Selenium and Human Cancer Risk

“…Rather, we focus on RCTs that were specifically designed to estimate the effects of Se administration on cancer risk, the majority of which were carried out in specific patient populations in the United States [ 93 – 97 ] and in France [ 98 ], and in one case in the general U.S. population [ 99 , 100 ]. The patient populations involved in such studies were nonmelanoma skin cancer patients [ 93 – 95 ], individuals at high risk of prostatic neoplasm [ 96 , 97 ] or breast cancer [ 101 ], and organ transplant recipients [ 98 ]. Among these trials, the two largest, the Nutritional Prevention of Cancer (NPC) Trial and the Selenium and Vitamin E Cancer Prevention Trial (SELECT), have received the greatest attention from both the general population and the scientific community.…”

“…Another randomized double-blind trial of considerable interest was conducted in Poland with a group of healthy women who were carriers of the BRCA1 mutation and thus at high risk for breast cancer [ 101 ]. Lubinski and colleagues randomized 1135 female BRCA1 mutation carriers to 250 μ g/day of Se as selenite or placebo for 6 to 62 months (median follow-up 35 months).…”

“…Lubinski and colleagues randomized 1135 female BRCA1 mutation carriers to 250 μ g/day of Se as selenite or placebo for 6 to 62 months (median follow-up 35 months). During follow-up, 60 incident breast cancers were diagnosed among Se-supplemented women in comparison with 45 cases among placebo-administered women (RR 1.4, 95% CI 0.9–2.0) [ 101 ]. Such results, which were mirrored in findings on primary breast cancer, contralateral breast cancer, and ovarian cancer, suggest not just a lack of any beneficial effect of Se on breast cancer in these high-risk women but the possibility of increased risk.…”