The World Cancer Research Fund/American Association for Cancer Research (WCRF/AICR) has published eight nutrition-related recommendations for the prevention of cancer. However, few prospective studies have examined these recommendations by breast cancer hormone receptor subtype and only one case-control study has included the dietary supplements recommendation in their evaluation. We investigated whether adherence to the WCRF/AICR cancer prevention recommendations was associated with breast cancer incidence, overall and by hormone receptor subtype, in the Swedish Mammography Cohort. Among 31,514 primarily postmenopausal women diet and lifestyle factors were assessed with a self-administered food frequency questionnaire. A score was constructed based on adherence to the recommendations for body fatness, physical activity, energy density, plant foods, animal foods, alcoholic drinks and dietary supplements (score range 0-7). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,388 cases of breast cancer were identified. Women who met six to seven recommendations had a 51% decreased risk of breast cancer compared to women meeting only zero to two recommendations (95% CI = 0.35-0.70). The association between each additional recommendation met and breast cancer risk was strongest for the ER-positive/PR-positive subtype (HR = 0.86; 95% CI = 0.79-0.94), while for the ER-negative/PR-negative subtype the individual recommendations regarding plant and animal foods were most strongly associated with reduced risk. Our findings support that adherence to the WCRF/AICR recommendations reduces breast cancer risk in a population of primarily postmenopausal women. Promoting these recommendations to the public could help reduce breast cancer incidence.
BACKGROUND: Familial breast cancers are known to be of early onset. This article provides differences in the age of onset of breast cancer and death by breast cancer between women with and without a family history. METHODS: The Swedish Family-Cancer Database was used to estimate the cumulative risk of breast cancer and death by breast cancer according to family history with a stratified Cox model. Family history was defined separately for affected mother or sister considering their diagnostic ages. RESULTS: The age to reach the same cumulative incidence as women without family history decreased with decreasing diagnostic age of the affected relative. Women with a maternal history reached the risk of women lacking a family history at the age of 50 years between 12.3 (mother affected 82 years) earlier. The trend for breast cancer mortality was essentially similar. CONCLUSIONS: Women with mother or sister affected by breast cancer are diagnosed and die at earlier ages than do women without family history. The differences depend on the diagnostic age of the affected relative. The present data may provide a rationale to derive recommendations for the starting age of screening in women with affected family members.
Incidence rates of breast cancer among women with a BRCA1 mutation vary according to their reproductive histories and country of residence. To measure cancer incidence, it is best to follow-up cohort of healthy women prospectively. We followed up a cohort of 675 women with a BRCA1 mutation who did not have breast or ovarian cancer before inclusion and who had a normal clinical examination and mammography at first visit. After a mean of 7.1 years, 98 incident cases of breast cancer were recorded in the cohort. Annual cancer incidence rates were calculated, and based on these, a penetrance curve was constructed. The average annual cancer risk for the Norwegian women from age 25 to 70 was 2.0%. Founder mutations had lower incidence rate (1.7%) than less frequent mutations (2.5%) (p = 0.03). The peak incidence (3.1% annual risk) was observed in women from age 50 to 59. The age-specific annual incidence rates and penetrance estimate were compared with published figures for women from North America and from Poland. The risk of breast cancer to age 70 was estimated to be 61% for women from Norway, compared with 55% for women from Poland and 69% for women from North America.
We aimed to estimate the effect of alcohol consumption on breast cancer risk and to test whether overweight and obesity modifies this association.
We included in the analysis 45,233 women enrolled in the Swedish Women's Lifestyle and Health study between 1991 and 1992. Participants were followed for occurrence of breast cancer and death until December 2009. Poisson regression models were used, and analyses were done for overall breast cancer and for estrogen receptor positive or negative (ER+, ER-) and progesterone receptor positive and negative (PR+, PR-) tumors separately.
A total of 1,385 breast cancer cases were ascertained during the follow-up period. Overall, we found no statistically significant association between alcohol intake and breast cancer risk after adjustment for confounding, with an estimated relative risk (RR) of 1.01 (95 % CI: 0.98-1.04) for an increment in alcohol consumption of 5 g/day. A statistically significant elevated breast cancer risk associated with higher alcohol consumption was found only among women with BMI =25 (RR 1.03, 95 % CI 1.0-1.05 per 5 g/day increase).
An increase in breast cancer risk with higher alcohol consumption was found for breast cancers in women with a BMI =25 kg/m(2).
Cites: Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1203-1222564867
Some studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. We aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk.
We conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. We studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. The statistically significant odds ratios were tested for noteworthiness using two Bayesian tests: false positive report probability (FPRP) and Bayesian false discovery probability (BFDP).
In the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2 (rs17024926), ROR-b (rs3903529, rs3750420), MTNR1A (rs131113549) and PER3 (rs1012477).
Significant and noteworthy associations between several polymorphisms in circadian genes, night work and breast cancer risk were found among nurses who had worked at least three consecutive night shifts.
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Based on a population-based cohort study, Olsson et al.  found significant evidence for elevated incidence of breast and ovarian cancers among female first-degree relatives of men with breast cancer. Using an extension of logistic regressive models we investigate whether, after allowing for multifactorial familial correlations, single locus segregation could be the cause of the elevated incidence in these families. The logit for a given sib in the class D logistic regressive model depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as being computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sibling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysis. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the models we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This could either be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.
The increase in clinical trials with androgen receptor (AR)-targeting drugs emphasizes the need of clarifying the role of AR expression in different breast cancer subtypes. AR confers good prognosis in estrogen receptor positive (ER+) breast cancer, but its role in ER-negative (ER-) breast cancer is unclear. The aim of this study was to elaborate on previous findings of a differential prognostic role for AR depending on ER status, using breast cancer mortality (BCM) as endpoint, in a population-based cohort from the Malmö Diet and Cancer Study.
Immunohistochemical AR expression was assessed in 910 women with invasive breast cancer diagnosed 1991-2010, supplemented with clinicopathological information, vital status, and cause of death, with the last follow-up in December 2014 (median 10 years). Survival analyses according to AR status and AR/ER combinations were performed.
AR expression was available for 671 tumors. AR+ (n = 573, 85%) was associated with favorable established tumor markers and lower BCM in univariable analysis, especially during the first 5 years following diagnosis [HR 0.4; 95% confidence intervals (CI) 0.2-0.7]. Multivariable analysis for short-term follow-up indicated higher BCM among patients with AR+ER- tumors (HR 3.5; 95% CI 1.4-9.1) than other AR and ER combinations.
AR expression added prognostic information to ER expression with respect to short-term prognosis. The worst prognosis was seen for patients with AR+/ER- tumors in short-term follow-up, supporting the pre-specified hypothesis. However, larger cohorts are needed for further characterization of the role of AR expression in ER- breast cancer.
Cites: J Natl Cancer Inst. 2014 Jan;106(1):djt319 PMID 24273215
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The breast-ovary cancer-family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17q12-q21. The majority, but not all, of breast-ovary cancer families show linkage to this susceptibility locus, designated BRCA1. We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer. These families contain either a total of three or more cases of early-onset (before age 60 years) breast cancer or ovarian cancer. All families contained at least one case of ovarian cancer. Overall, an estimated 76% of the 145 families are linked to the BRCA1 locus. None of the 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%-100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1. These data suggest that the breast-ovarian cancer-family syndrome is genetically heterogeneous. However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations.
Oxidative stress may be important in carcinogenesis and a possible risk factor for breast cancer. The urinary excretion of oxidatively generated biomolecules, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), represents biomarkers of oxidative stress, reflecting the rate of global damage to DNA in steady state.
In a nested case-control design, we examined associations between urinary excretion of 8-oxodG and risk of breast cancer in a population-based cohort of 24,697 postmenopausal women aged 50 to 64 years with 3 to 7 years follow-up. The accruing cases of breast cancer were matched to controls by age at diagnosis, baseline age, and hormone replacement therapy (HRT). Spot urine samples collected at entry was analyzed for 8-oxodG by high-performance liquid chromatography with electrochemical detection. Incidence rate ratio (IRR; 95% confidence intervals) based on 336 matched pairs with all information was estimated per unit increase in 8-oxodG divided by creatinine for all and estrogen receptor (ER) positive and negative breast cancers.
There was a borderline significant positive association between 8-oxodG and risk of all breast cancer (IRR: 1.08; 1.00-1.17 per unit increase in nmol/mmol creatinine). This association was significant with respect to the risk of ER-positive cancer (IRR: 1.11; 1.01-1.23) and among women not using HRT (IRR: 1.11; 0.97-1.26) or with low dietary iron intake (IRR: 1.10; 1.06-1.37 per unit increase) for all breast cancer.
We observed positive association between 8-oxodG excretion and risk of especially ER-positive breast cancer.
Our results suggest that oxidative stress with damage to DNA is important for the development of breast cancer.
Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T-->C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1-3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1. 9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41-1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women. Int. J. Cancer (Pred. Oncol.) 84:350-353, 1999.