Common genetic polymorphisms of AURKA and prostate cancer risk

Purpose  AURKA is a centrosome-associated serine/threonine kinase involved in mitotic chromosomal segregation. The AURKA gene is located on chromosome 20q13, also known as HPC20 prostate cancer susceptibility locus. Therefore, we investigated in this Caucasian case–control study two single nucleotide polymorphisms (SNPs) of the AURKA gene, rs8173 located in the 3′-untranslated region (G1891C) and rs2273535 in exon 5 (Phe31Ile), and their association with prostate cancer risk. Methods  DNA was extracted from peripheral blood of 824 prostate cancer patients and 1,081 control patients with benign prostatic hyperplasia (BPH). Genotypes were determined using 5′-nuclease TaqMan assays. Multiple logistic regressions were performed to calculate odds ratios (OR) and confidence intervals (CI) and to adjust for confounders. Results  The odds ratios calculated relative to the wild-type were for the homozygous polymorphic genotypes 1.11 (95% CI = 0.70–1.76) for rs8173 and 1.32 (95% CI = 0.76–2.31) for rs2273535, respectively. Stratified analyses according to Gleason score showed also no statistically significant association for the investigated polymorphisms and prostate cancer risk. Conclusions  The two investigated SNPs in AURKA were not found to be associated with prostate cancer risk. Other common SNPs of AURKA should be investigated in further studies because of its location on a prostate cancer susceptibility locus.     

Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women’s Health Study

Two single nucleotide polymorphisms (SNPs), rs4415084, and rs10941679 on chromosome 5p12 were associated with risk of breast cancer in a recent genome-wide association study (GWAS) of women of European ancestry. Both SNPs are located in a large high-LD region and the causal variant(s) are still unknown. We conducted a nested case–control study in a cohort of African American women to replicate and narrow the region carrying the causal variant(s). We evaluated 14 tagging SNPs in a 98 kb LD block surrounding the index SNPs in 886 breast cancer cases and 1,089 controls from the Black Women’s Health Study. We used the Cochran–Armitage trend test to assess association with breast cancer risk. Odds ratios were derived from logistic regression analyses adjusted for potential confounders including percent European admixture. We confirmed the reported association of rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the original study, observed a stronger association with estrogen receptor positive tumors (P = 0.03). We identified four other SNPs (rs6451770, rs12515012, rs13156930, and rs16901937) associated with risk of breast cancer at the nominal alpha value of 0.05; all of them were located in a 59 kb HapMap YRI LD block. After correction for multiple testing, the association with SNP rs16901937 remained significant (P permutated = 0.038). The G allele was associated with a 21% increased risk of breast cancer overall and with a 32% increase in tumors positive for both estrogen and progesterone receptors. The present results from an African ancestry (AA) population confirm the presence of breast cancer susceptibility genetic variants in the chromosome 5p12 region. We successfully used the shorter range of LD in our AA sample to refine the localization of the putative causal variant.     

Family-based genetic association study of insulin-like growth factor I microsatellite markers and premenopausal breast cancer risk

Several studies suggest that higher circulating insulin-like growth factor I (IGF-I) levels are associated with premenopausal breast cancer risk. Breast cancer risk and circulating IGF-I concentration appear to be partly heritable, thus genetic variation at IGF1 could influence IGF-I levels and breast cancer risk. We investigated the association of IGF1 CA repeat variants with premenopausal breast cancer risk using a family-based design. The study sample included 840 families from the Ontario Familial Breast Cancer Registry (OFBCR) and the Australian Breast Cancer Family Registry (ABCFR). Three CA repeat variants, at 5′, 3′, and in intron 2 were genotyped (5′CA, 3′CA, In2CA). We found several nominally significant associations. The 5′CA-21 allele (P = 0.03) and In2CA-212 allele (P = 0.04) were associated with lower risk, and the In2CA-216 allele with higher risk (P = 0.04) for the combined ABCFR–OFBCR. These associations were not significant after taking into account multiple comparisons. In2CA-216 was more strongly associated with risk when we used a recessive instead of an additive model (P = 0.01). 5′CA alleles of repeat length 18–20 were associated with higher risk (P = 0.02), and 5′CA alleles of >20 repeats were associated with lower risk (P = 0.01). These associations were significant in the OFBCR (In2CA-216 recessive, P = 0.02; 5′CA 18–20 and >20 allele grouping, P = 0.01) but not strongly supported by the ABCFR (In2CA-216 recessive, P = 0.14; 5′CA 18–20, P = 0.25; 5′CA >20, P = 0.20). The associations we found could be due to chance as many comparisons were made. Our results do not strongly support an association between these IGF1 variants and breast cancer risk.     

A <Emphasis Type="Italic">CYP19</Emphasis> (aromatase) polymorphism is associated with increased premenopausal breast cancer risk

Due to the established association between estrogen levels and breast cancer risk, polymorphic variation in genes regulating estrogen levels is thought to be related to breast cancer risk. Aromatase, the protein product of the CYP19 gene, is involved in the production of endogenous estrogens via androgen conversion. We examined whether polymorphic variation in CYP19 associated with increased breast cancer risk in a population based case-control study. We examined two single nucleotide polymorphisms (SNP), rs1008805 (A/G) and rs730154 (C/T), which have been shown to tag SNPs within two different haplotype blocks in CYP19. Among premenopausal women, the presence of at least one G allele at rs1008805 was significantly associated with an increase in the risk of breast cancer (OR = 1.72 [95% CI, 1.20–2.49]), especially with estrogen and progesterone receptor negative breast cancer (OR = 3.89 [1.74–8.70] and OR = 2.52 [1.26–5.05], respectively). No association was observed among postmenopausal women (OR = 1.06 [0.82–1.36]). There was no significant association between rs730154 and breast cancer, regardless of menopausal status. Our results suggest that premenopausal women carrying the G allele at CYP19 rs1008805 have increased risk of breast cancer. The finding supports the potential role of variation in estrogen biosynthesis genes in premenopausal breast cancer risk.     

Low penetrance breast cancer predisposition SNPs are site specific

Large scale association studies have identified low penetrance susceptibility alleles that predispose to breast cancer. A locus on chromosome 8q24.21 has been shown to harbour variants that predispose to breast, ovarian, colorectal and prostate cancer. The finding of risk variants clustering at 8q24 suggests that there may be common susceptibility alleles that predispose to more than one epithelial cancer. The aim of this study was firstly to determine whether previously identified breast cancer susceptibility alleles are associated with sporadic breast cancer in the West of Ireland and secondly to ascertain whether there are susceptibility alleles that predispose to all three common epithelial cancers (breast, prostate, colon). We genotyped a panel of 24 SNPs that have recently been shown to predispose to prostate, colorectal or breast cancer in 988 sporadic breast cancer cases and 1,016 controls from the West of Ireland. We then combined our data with publicly available datasets using standard techniques of meta-analysis. The known breast cancer SNPs rs13281615, rs2981582 and rs3803662 were confirmed as associated with breast cancer risk (P _{allelic test} = 1.8 × 10⁻², OR = 1.17; P _{allelic test} = 2.2 × 10⁻³, OR = 1.22; P _{allelic test} = 5.1 × 10⁻², OR = 1.15, respectively) in the West of Ireland cohort. For the remaining five breast cancer SNPs that were studied there was no evidence of an association with breast cancer in the West Ireland population (P _{allelic test} > 6.5 × 10⁻²). There was also no association between any of the prostate or colorectal susceptibility SNPs, whether at 8q24 or elsewhere, with breast cancer risk. Meta-analysis confirmed that all susceptibility SNPs were site specific, with the exception of rs6983269 which is known to predispose to both colorectal and prostate cancer. This study confirms that susceptibility loci at FGFR2, 8q24 and TNCR9 predispose to sporadic breast cancer in the West of Ireland. It also suggests that low penetrance susceptibility SNPs for breast, prostate and colorectal cancer are distinct. Although 8q24 harbours variants that predispose to all three cancers, the susceptibility loci within the region appear to be specific for the different cancer types with the exception of rs6983269 in colon and prostate cancer. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

DNA-repair genetic polymorphisms and risk of breast cancer in Cyprus

The DNA repair pathway is known to play a role in the etiology of breast cancer. A number of studies have demonstrated that common germline variants in genes involved in the DNA repair pathway influence breast cancer risk. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 12 single nucleotide polymorphisms (SNPs) in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. We found significant associations with breast cancer for SNPs in the BRCA2 and MRE11A genes. Carriers of the BRCA2 rs1799944 variant (991 Asp) were found to have an increased risk of breast cancer (OR = 1.41, 95% CI 1.08–1.83, P = 0.01) with P _trend = 0.0076. Homozygous carriers of the MRE11A rs601341 A allele had an increased risk of breast cancer (OR = 1.36, 95% CI 1.08–1.71, P = 0.009) with P _trend = 0.0087. This study suggests that genetic variants in BRCA2 and MRE11A are associated with breast cancer risk.     

Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Objective  A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism. Methods  We prospectively examined the diabetes–prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Results  During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68–0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62–0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum ≥8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74–1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87–3.07; BMI < 25 kg/m²) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07–2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively). Conclusion  In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.     

Body size and risk of prostate cancer in Jamaican men

We investigated the associations between body size and risk of prostate cancer in a hospital-based case–control study in Jamaica. Height, weight, waist, and hip circumference were measured at enrollment, and data collected on medical and lifestyle factors for newly diagnosed cases (n = 243) and controls (n = 275). Compared with men in the normal range of waist-hip ratio (WHR), men with WHR ≥0.95 were at greater risk of total prostate cancer (OR,1.72; CI, 1.01–3.00) and high-grade cancer (OR, 2.02; CI, 1.03–3.96). With additional control for BMI, the association with WHR remained significant for total prostate cancer (OR, 1.90; CI, 1.01–3.53) and high-grade disease (OR, 2.94; CI, 1.34–6.38). There was no association between waist circumference and cancer without control for BMI but after controlling for BMI, waist circumference >90 cm (OR, 2.45; CI, 1.01–5.94) and >102 cm (OR, 5.57; CI, 1.43–18.63) showed a dose–response relationship with high-grade disease. Height and BMI were not associated with risk of prostate cancer. Abdominal obesity may be associated with risk of high-grade prostate cancer. Risk may be greater in those with higher abdominal obesity relative to overall size. The results further highlight the importance of investigating relationships by characteristics of the tumor.     

Reproductive factors and histologic subtype in relation to mortality after a breast cancer diagnosis

Evidence suggests that certain reproductive factors are more strongly associated with the incidence of lobular than of ductal breast cancer. The mechanisms influencing breast cancer incidence histology may also affect survival. Women with invasive breast cancer (N = 22,302) diagnosed during 1986–2005 were enrolled in a series of population-based studies in three US states. Participants completed telephone interviews regarding reproductive exposures and other breast cancer risk factors. Histologic subtype was obtained from state cancer registries. Vital status and cause of death were determined through December 2006 using the National Death Index. Women were followed for 9.8 years on average with 3,050 breast cancer deaths documented. Adjusted hazard rate ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression models for breast cancer-specific and all-cause mortality. Parity was inversely associated with breast cancer-specific mortality (P _Trend = 0.002). Associations were similar though attenuated for all-cause mortality. In women diagnosed with ductal breast cancer, a 15% reduction in breast cancer-specific mortality was observed in women with five or more children when compared to those with no children (HR = 0.85, 95% CI: 0.73–1.00). A similar inverse though non-significant association was observed in women with lobular subtype (HR = 0.70, 95% CI: 0.43–1.14). The trend did not extend to mixed ductal–lobular breast cancer. Age at first birth had no consistent relationship with breast cancer-specific or all-cause mortality. We found increasing parity reduced mortality in ductal and lobular breast cancer. The number of full-term births, rather than age at first birth, has an effect on both breast cancer-specific and overall mortality.     

Interleukin-22 genetic polymorphisms and risk of colon cancer

Interleukin-22 (IL-22) is a member of the IL-10 family of anti-inflammatory cytokines that mediates epithelial immunity. IL-22 expression is enhanced in inflamed colon mucosa in individuals with inflammatory bowel disease. We carried out an association study to examine the hypothesis that common variation in the IL-22 gene is associated with risk of colon cancer. Seven tagging SNPs were genotyped in 561 colon cancer cases and 722 population controls. Information on lifestyle risk factors was collected via a self-administered questionnaire. The rs1179251 SNP conferred an estimated odds ratio (OR) of 1.46 (95% CI = 1.04–2.05) and 2.10 (95% CI = 0.66–6.66), respectively, for those heterozygous and homozygous for the G variant (p _additive = 0.013) after adjustment for age, gender, and race; the OR assuming a dominant model was 1.50 (95% CI = 1.05–2.08, p _dominant = 0.016). No other SNP was statistically significantly associated with colon cancer risk. Haplotype analysis found that one haplotype containing the rs1179251 G allele gave an estimated 52% increase in risk of colon cancer for individuals with at least one copy (OR = 1.52, 95% CI = 1.12–2.06, p = 0.0073). Our findings suggest that the rs1179251 SNP in IL-22 is associated with risk of colon cancer.     

Use of blood-pressure-lowering medication and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort

Objectives  To examine the association between use of anti-hypertensive drugs and prostate cancer incidence among 48,389 men in the Cancer Prevention Study II Nutrition Cohort. Methods  Proportional hazards models were used to calculate rate ratios (RR) for use of Beta-Blockers (BBs), Calcium Channel Blockers (CCBs), and ACE Inhibitors (ACE) and incident prostate cancer in time-dependent analyses. Results  During follow-up from 1997 to 2005, we identified 3,031 cases of incident prostate cancer. Anti-hypertensive use was associated with slightly decreased risk of all (RR = 0.90, 95% CI 0.83–0.98) and organ-confined low-grade prostate cancer (RR = 0.89, 95% CI 0.81–0.99), but was not statistically significantly associated with aggressive-fatal prostate cancer (RR = 0.93, 95% CI 0.79–1.10). BB and ACE inhibitor treatment was associated with an approximately 10% lower risk for all prostate cancer in models adjusted for age and race. These associations were attenuated and lost statistical significance when adjusted for history of heart disease. No trend with duration of use was detected. Conclusions  These results do not support the hypothesis that anti-hypertensive medication is strongly associated with risk of prostate cancer. Confounding by concurrent illness may explain inverse associations seen in other studies.     

Physical activity, sedentary behavior, and the risk of colon and rectal cancer in the NIH-AARP Diet and Health Study

Objective  In order to prospectively investigate physical activity at varying intensities and sedentary behavior in relation to colorectal cancer. Methods  We considered 488,720 participants of the NIH-AARP Diet and Health Study who were aged 50–71 years at baseline in 1995–1996. Through 31 December, 2003, we identified 3,240 and 1,482 colorectal cancers among men and women, respectively. We estimated multivariable relative risks (RR) and 95% confidence intervals (CI) of colorectal cancer using Cox regression. Results  Engaging in exercise/sports five or more times per week compared to never or rarely exercising was associated with a reduced risk of colon cancer among men (p = 0.001; RR = 0.79, 95% CI = 0.68–0.91) and a suggestive decrease in risk among women (p = 0.376; RR = 0.85, 95% CI = 0.70–1.04). Engaging in exercise/sports was also associated with a decreased risk of rectal cancer in men (P = 0.074; RR comparing extreme categories = 0.76, 95% CI = 0.61–0.94). In men, we observed inverse relations of both low intensity (p = 0.017; RR = 0.81, 95% CI = 0.65–1.00 for ≥7 h/week) and moderate to vigorous intensity activity (p = 0.037; RR = 0.82, 95% CI = 0.67–0.99 for ≥7 h/week) to colon cancer risk. In contrast, sedentary behavior (time spent watching television/videos) was positively associated with colon cancer (p < 0.001; RR = 1.61, 95% CI = 1.14–2.27 for ≥9 h/day) among men. Similar, but less pronounced relations were observed in women. Conclusion  Engaging in physical activity of any intensity is associated with reductions in colon and rectal cancer risk. Conversely, time spent sedentary is associated with increased colon cancer risk.     

<Emphasis Type="Italic">AXIN2</Emphasis> polymorphism and its association with prostate cancer in a Turkish population

Polymorphism of AXIN2, a component of Wnt signaling, has been shown to play a role in tumorigenesis and dysregulated in cancer cells. In order to find out if AXIN2 polymorphism is a risk factor for prostate cancer, we analyzed eight polymorphic regions of this gene in 84 patients with prostate cancer and compared the results with 100 healthy controls in a Turkish population using PCR–RFLP methods. The genotype frequencies and risk factors of prostate cancer and control groups were analyzed by Chi-square test. We found a statistically significant result between prostate cancer risk and AXIN2 Intron2-956 + 16A/G (rs35285779) SNP. The frequency of the homozygous G/G (0%) and heterozygous A/G (18%) genotypes was significantly less in patients with prostate cancer than in healthy controls (7 and 32%, respectively) (P < 0.05) for this SNP. When compared with the wild-type A/A genotype of the controls, prostate cancer patients with the A/G and G/G genotype showed reduced risk of cancer; the adjusted odds ratio (OR) for patients with the homozygous G/G genotype was 0.87 (95% CI: 0.81–0.95) and for heterozygous A/G genotype was 0.42 (95% CI: 0.20–0.85). We found no statistically significant association between controls and prostate cancer for other seven SNPs of AXIN2 including Exon1-148 C/T (rs2240308), Exon1-432 T/C (rs2240308), Exon5-1365 G/A (rs9915936), Exon5-1386 C/T (rs1133683), Intron5-1712 + 19 T/G, Exon7-2062 C/T, and Intron7-2141 + 73 G/A (rs4072245) (P > 0.05). These results suggest that the AXIN2 Intron2 rs35285779 SNP is associated with development of prostate cancer as a protective SNP, while an association between other seven SNPs of the AXIN2 and risk of prostate cancer was not observed.     

Vitamin D receptor variants and breast cancer risk in the Polish population

The aim of the study was to determine whether four VDR gene single nucleotide polymorphisms (SNPs: rs1544410, rs731236, rs10735810 and rs4516035) are associated with breast cancer risk in Polish population. Two independent series of female patients were employed: 960 consecutive breast cancer cases, and 800 unselected early onset cases diagnosed under the age of 51. The control group for the consecutive breast cancer cases consisted of 960 healthy, age-matched women with a negative cancer family history. 550 healthy women, aged 51 or less, with negative cancer family history were selected as the independent controls for the early onset breast cancer cases. The frequencies of the VDR polymorphisms in the unselected cases when compared to the respective control population failed to reveal any association between the individual SNPs and disease. Examination of the group of early-onset patients, revealed an association between rs10735810 and increased breast cancer risk. Heterozygous carriers for the change had an OR = 1.73 (95% CI 1.33–2.26, P < 0.0001) and homozygous carriers OR = 2.34 (95% CI 1.71–3.21, P < 0.0001). The remaining three examined SNPs failed to show any association with disease risk. In summary, this study has identified an association between the VDR gene and early onset breast cancer risk in the Polish population.     

Hypercholesterolemia and prostate cancer: a hospital-based case–control study

Objective  High levels of serum cholesterol have been proposed to increase the risk of prostate cancer but the epidemiologic evidence is limited. Methods  We conducted a hospital-based case–control study in Fargo, ND, USA, to examine the association between hypercholesterolemia and prostate cancer. Cases were men with incident, histologically confirmed prostate cancer. Controls were men without clinical cancer who were seen at the same hospital for an annual physical exam. Demographic and clinical data were abstracted from patients’ medical charts. Results  From a patient population aged 50 to 74 years old, we obtained data on 312 White cases and 319 White controls. Hypercholesterolemia was defined as total cholesterol greater than 5.17 (mmol/l). Univariate logistic regression showed a significant association between hypercholesterolemia and prostate cancer (odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.19–2.27). This association changed only slightly after adjustment for age, family history of prostate cancer, body mass index, type 2 diabetes, smoking, and multivitamin use (OR = 1.58, 95% CI: 1.11–2.24). A significant association was found between low HDL and prostate cancer (OR = 1.57, 95% CI: 1.04–2.36). High LDL was associated with a 60% increased risk for prostate cancer (OR = 1.60, 95% CI: 1.09–2.34). Compared to never smokers, current smokers had an 84% increased risk for prostate cancer (OR = 1.84, 95% CI: 1.09–3.13). Conclusion  This study adds to recent evidence that hypercholesterolemia may increase the risk of prostate cancer in white men.     

Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus

Population-based studies have reported significant associations between specific genetic polymorphisms and breast cancer susceptibility. A number of studies have demonstrated that common variants of genes involved in the DNA repair pathway act as low penetrance breast cancer susceptibility alleles. We aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the DNA repair genes XRCC1, XRCC2 and XRCC3 and breast cancer in MASTOS, a population-based case–control study of 1,109 Cypriot women with breast cancer diagnosed between 40 and 70 years and 1,177 age-matched healthy controls. Five coding SNPs were genotyped including rs1799782, rs25489 and rs25487 in XRCC1, rs3218536 in XRCC2 and rs861539 in XRCC3. Homozygous XRCC1 280His carriers had an increased risk of breast cancer (odds ratio 4.68; 95% CI 1.01–21.7; P = 0.03). The XRCC2 188His allele was associated with a marginal protective effect for breast cancer (odds ratio 0.79; 95% CI 0.62–1.00; P = 0.05). No significant associations were observed between the other three SNPs and breast cancer. This study suggests that genetic variation in SNPs in XRCC1 and XRCC2 genes may influence breast cancer susceptibility.     

Obesity and breast cancer survival in ethnically diverse postmenopausal women: the Multiethnic Cohort Study

Breast cancer survival has been found to be lower in obese women, but few studies have evaluated ethnic variations in this association. This study examined all-cause and breast cancer-specific survival by body mass index (BMI) in the Multiethnic Cohort (MEC) study for African American, Native Hawaiian, Japanese American, Latino, and Caucasian women. Female MEC participants free of breast cancer, aged ≥50 years at cohort entry, and diagnosed with primary invasive breast cancer during follow-up were included in the analyses (n = 3,842). Cox proportional hazards regression was used to estimate the effect of pre-diagnostic adult BMI (<22.5, 22.5–24.9, 25.0–29.9, ≥30 kg/m²) on the risk of mortality. Mean age at diagnosis was 68.8 years (range 50–89 years). During a mean follow-up of 6.2 ± 3.8 years after diagnosis, there were 804 deaths that included 376 breast cancer-specific deaths. After adjustment for breast cancer characteristics, including hormone receptor status, stage at diagnosis, and treatment, obese women had a higher risk of all-cause [hazard ratio (HR) = 1.54; 95% confidence interval (CI): 1.23, 1.91] and breast cancer-specific (HR = 1.45; 95% CI: 1.05, 2.00) mortality compared to women with high-normal BMI; however, being overweight did not affect survival. There was no evidence of ethnic differences in the BMI effect on all-cause (P _interaction = 0.87) or breast cancer-specific (P _interaction = 0.63) mortality. Our findings are consistent with the literature that maintaining moderate weight throughout adult life may be beneficial for breast cancer survival in women and this appears to hold for all ethnic groups.     

Melatonin pathway genes and breast cancer risk among Chinese women

Previous studies suggest that melatonin may act on cancer growth through a variety of mechanisms, most notably by direct anti-proliferative effects on breast cancer cells and via interactions with the estrogen pathway. Three genes are largely responsible for mediating the downstream effects of melatonin: melatonin receptors 1a and 1b (MTNR1a and MTNR1b), and arylalkylamine N-acetyltransferase (AANAT). It is hypothesized that genetic variation in these genes may lead to altered protein production or function. To address this question, we conducted a comprehensive evaluation of the association between common single nucleotide polymorphisms (SNPs) in the MTNR1a, MTNR1b, and AANAT genes and breast cancer risk among 2,073 cases and 2,083 controls, using a two-stage analysis of genome-wide association data among women of the Shanghai Breast Cancer Study. Results demonstrate two SNPs were consistently associated with breast cancer risk across both study stages. Compared with MTNR1b rs10765576 major allele carriers (GG or GA), a decreased risk of breast cancer was associated with the AA genotype (OR = 0.78, 95% CI = 0.62–0.97, P = 0.0281). Although no overall association was seen in the combined analysis, the effect of MTNR1a rs7665392 was found to vary by menopausal status (P-value for interaction = 0.001). Premenopausal women with the GG genotype were at increased risk for breast cancer compared with major allele carriers (TT or TG) (OR = 1.57, 95% CI = 1.07–2.31, P = 0.020), while postmenopausal women were at decreased risk (OR = 0.58, 95% 0.36–0.95, P = 0.030). No significant breast cancer associations were found for variants in the AANAT gene. These results suggest that common genetic variation in the MTNR1a and 1b genes may contribute to breast cancer susceptibility, and that associations may vary by menopausal status. Given that multiple variants in high linkage disequilibrium with MTNR1b rs76653292 have been associated with altered function or expression of insulin and glucose family members, further research may focus on clarifying this relationship.     

The association of atopic diseases with breast, prostate, and colorectal cancers: a meta-analysis

There is a long-standing interest in finding whether allergic disorders cause or prevent cancer. We meta-analyzed associations of allergies with prostate, breast, and colorectal cancers. We searched MEDLINE, EMBASE, and Web of Science between 1966 and 2008 and eligible reference lists. A total of 16 observational studies were included. Meta-analyses revealed no evidence that asthma, hay fever, or ‘any allergy’ are associated with cancers of the breast (relative risk, RR = 0.93, 95% CI: 0.73–1.19 for asthma; 1.04, 0.94–1.16 for hay fever; 1.01, 0.94–1.08 for any allergy); prostate (RR = 0.93, 95% CI: 0.76–1.15 for asthma; 0.96, 0.87–1.05 for hay fever; 1.01, 0.87–1.17 for any allergy); or colorectum (RR = 0.95, 95% CI: 0.77–1.16 for asthma; 0.95, 0.86–1.05 for hay fever; 0.94, 0.85–1.04 for any allergy). There was a positive association of atopy (assessed by allergen-specific IgE or skin prick testing) with prostate cancer (RR = 1.43, 95% CI: 1.08–1.91), but not breast (1.18, 0.90–1.55) or colorectal (1.32, 0.69–2.53) cancers. There is little epidemiological support for the immune surveillance theory or antigenic stimulation theory in breast or colorectal carcinogenesis. The findings for prostate cancer warrant further investigation.     

Vitamin and mineral use and risk of prostate cancer: the case–control surveillance study

Background  Many studies have evaluated the association between vitamin and mineral supplement use and the risk of prostate cancer, with inconclusive results. Methods  The authors examined the relation of use of multivitamins as well as several single vitamin and mineral supplements to the risk of prostate cancer risk among 1,706 prostate cancer cases and 2,404 matched controls using data from the hospital-based case–control surveillance study conducted in the United States. Odds ratios (OR) and 95% confidence intervals (CI) for risk of prostate cancer were estimated using conditional logistic regression model. Results  For use of multivitamins that did not contain zinc, the multivariable odds ratios of prostate cancer were 0.6 for 1–4 years, 0.8 for 5–9 years, and 1.2 for 10 years or more, respectively (p for trend = 0.70). Men who used zinc for ten years or more, either in a multivitamin or as a supplement, had an approximately two-fold (OR = 1.9, 95% CI: 1.0, 3.6) increased risk of prostate cancer. Vitamin E, beta-carotene, folate, and selenium use were not significantly associated with increased risk of prostate cancer. Conclusion  The finding that long-term zinc intake from multivitamins or single supplements was associated with a doubling in risk of prostate cancer adds to the growing evidence for an unfavorable effect of zinc on prostate cancer carcinogenesis.