Polymorphisms in the ICAM gene locus are not associated with breast cancer Risk.
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Breast Neoplasms↗
Biomedical subjects
David J Hunter
Publications and source records attributed to David J Hunter.
Lack of associations of selected variants in genes involved in cell cycle and apoptosis with skin cancer risk.
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Adult↗
Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer.
The Ala(222)Val single nucleotide polymorphism (SNP) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in one-carbon metabolism, has been associated with colorectal cancer risk. Many enzymes are involved in one-carbon metabolism, and SNPs in the corresponding genes may play a role in colorectal carcinogenesis. We examined 24 nonsynonymous SNPs in 13 genes involved in the one-carbon metabolism pathway in relation to the risk of colorectal cancer in a case-control study nested in the Nurses' Health Study and the Health Professionals Follow-up Study cohorts. Among 376 men and women with colorectal cancer and 849 controls, a reduced risk of colorectal cancer was observed for Val/Val versus Ala carriers of MTHFR Ala(222)Val [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.43-1.00]. An increased risk was suggested for the variant carrier genotypes versus homozygous wild-type for betaine hydroxymethyltransferase Arg(239)Gln (OR, 1.40; 95% CI, 1.07-1.83) and two linked SNPs in methionine synthase reductase, Ser(284)Thr (OR, 1.85; 95% CI, 1.05-3.27) and Arg(415)Cys (OR, 2.03; 95% CI, 1.15-3.56). The other SNPs were not associated with colorectal cancer risk. Also, none of the SNPs were associated with risk in subgroups of dietary methyl status or were jointly associated with colorectal cancer risk in combination with another SNP, except possibly SNPs in methionine synthase and transcobalamin II. However, these analyses of gene-diet interactions were limited in statistical power. Our results corroborate previous findings for MTHFR Ala(222)Val and suggest that other genes involved in one-carbon metabolism, particularly those that affect DNA methylation, may be associated with colorectal cancer risk.
Adult↗
A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
INTRODUCTION: Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/or androgen receptor (AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). METHODS: The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships (blocks) across the gene were then identified, and haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases and 7,480 controls). RESULTS: We found no association between any genetic variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed. CONCLUSION: Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.
Aged↗
Disclosure of sexual orientation and behavior in the Nurses' Health Study II: results from a pilot study.
OBJECTIVE: To examine disclosure of sexual orientation and response rates in a pilot study of questions on sexual orientation and gender of sexual partners in the Nurses' Health Study II. METHODS: A pilot questionnaire was mailed to random samples of 350 women from each of three marital status strata: never married, previously married, and currently married. We estimated prevalence of each category of sexual orientation in the pilot study. Response rates to the sexual orientation question for the pilot questionnaire and the 1995 cohort questionnaire were compared. RESULTS: The overall response rate to the pilot study was 78%. In the pilot study, 98% of women reported a sexual orientation of heterosexual, 0.1% bisexual, and 0.9% lesbian, with 0.7% either declining to answer, leaving the question blank, or categorizing themselves as none of the above, weighted for stratified sampling by marital status. The distribution of sexual orientation in the cohort study (N = 91,654) was similar. Asking women to participate in the pilot study of sexual orientation questions did not appear to cause participants to drop out of the cohort. Concordance between reported sexual orientation on the pilot study and the cohort study was high. CONCLUSIONS: Based on our experience, researchers may be encouraged to add questions on sexual orientation to large studies of women.
Bisexuality↗
Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II.
Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses' Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69-1.39; IGFBP-1, 0.95, 95% CI, 0.63-1.41; IGFBP-3, 1.10, 95% CI, 0.78-1.54; GH, 1.09, 95% CI, 0.82-1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.
Adult↗
Common variants of the endothelial nitric oxide synthase gene and the risk of coronary heart disease among U.S. diabetic men.
Endothelial nitric oxide synthase (eNOS) gene represents a promising candidate gene for coronary heart disease (CHD) because of its impact on eNOS activity. We systematically examined the associations of eight variants of the eNOS gene (two potentially functional variants [-786T>C and Glu298Asp] and six tagging single nucleotide polymorphisms) with CHD risk in a large cohort of diabetic patients. Among 861 diabetic men (>97% Caucasian) from the Health Professionals Follow-Up Study, 220 developed CHD, and 641 men without cardiovascular disease were used as control subjects. Genotype distributions of -786T>C and Glu298Asp polymorphisms were not significantly different between case and control subjects. CHD risk was significantly higher among men with the variant allele at the rs1541861 locus (intron 8 A/C) than men without it (adjusted odds ratio 1.5 [95% confidence interval 1.1-2.1]). Moreover, among control subjects, plasma soluble vascular cell adhesion molecule concentrations were significantly higher among carriers of this allele (P 0.019) and carriers of the variant allele of the -786T>C (P 0.010), or the Glu298Asp polymorphism (P 0.002), compared with noncarriers. In conclusion, our data suggested that -786T>C, Glu298Asp, and an intron 8 polymorphism of the eNOS gene are potentially involved in the atherogenic pathway among U.S. diabetic men.
Aged↗
Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men.
Emerging evidence indicates that variation in the transcription factor 7-like 2 (TCF7L2) gene may play a role in the pathogenesis of type 2 diabetes. In a prospective, nested, case-control study (n = 3,520) within the Nurses' Health Study (687 type 2 diabetic case and 1,051 control subjects) and the Health Professionals Follow-up Study (886 case and 896 control subjects), we examined the association of a common variant of the TCF7L2 gene (rs12255372 [T/G]) with type 2 diabetes risk among Caucasians. Frequencies of the T-allele were significantly higher among case than control subjects; each copy of the T-allele was associated with a 1.32-fold (P = 0.0002) and 1.53-fold (P < 0.0001) increased type 2 diabetes risk in women and men, respectively. The odds ratios (95% CI) associated with homozygous carriers of the T-allele were 1.86 (1.30-2.67) and 2.15 (1.48-3.13) in women and men, respectively. Population-attributable risks for diabetes associated with the T-allele were 14.8 and 22.3% for women and men, respectively. In a meta-analysis of 3,347 case and 3,947 control subjects, each copy of the T-allele was associated with a 1.48-fold increased risk (P < 10(-16)). Our findings confirm that the TCF7L2 gene represents an important locus for predicting inherited susceptibility to type 2 diabetes.
Adult↗
Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer.
Chronic inflammation has been hypothesized to be a risk factor for prostate cancer. The Toll-like receptor 4 (TLR4) presents the bacterial lipopolysaccharide (LPS), which interacts with ligand-binding protein and CD14 (LPS receptor) and activates expression of inflammatory genes through nuclear factor-kappaB and mitogen-activated protein kinase signaling. A previous case-control study found a modest association of a polymorphism in the TLR4 gene [11381G/C, GG versus GC/CC: odds ratio (OR), 1.26] with risk of prostate cancer. We assessed if sequence variants of TLR4 were associated with the risk of prostate cancer. In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped 16 common (>5%) single nucleotide polymorphisms (SNP) discovered in a resequencing study spanning TLR4 to test for association between sequence variation in TLR4 and prostate cancer. Homozygosity for the variant alleles of eight SNPs was associated with a statistically significantly lower risk of prostate cancer (TLR4_1893, TLR4_2032, TLR4_2437, TLR4_7764, TLR4_11912, TLR4_16649, TLR4_17050, and TLR4_17923), but the TLR4_15844 polymorphism corresponding to 11381G/C was not associated with prostate cancer (GG versus CG/CC: OR, 1.01; 95% confidence interval, 0.79-1.29). Six common haplotypes (cumulative frequency, 81%) were observed; the global test for association between haplotypes and prostate cancer was statistically significant (chi(2) = 14.8 on 6 degrees of freedom; P = 0.02). Two common haplotypes were statistically significantly associated with altered risk of prostate cancer. Inherited polymorphisms of the innate immune gene TLR4 are associated with risk of prostate cancer.
Adult↗
Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies.
CONTEXT: Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. OBJECTIVE: To evaluate the association between dietary fiber intake and risk of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725,628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. MAIN OUTCOME MEASURE: Incident colorectal cancer. RESULTS: During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR = 0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR = 0.94; 95% CI, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to <15 g/d, the pooled multivariate RR was 1.18 (95% CI, 1.05-1.31) for less than 10 g/d (11% of the overall study population); and RR, 1.00 (95% CI, 0.85-1.17) for 30 or more g/d. Fiber intake from cereals, fruits, and vegetables was not associated with risk of colorectal cancer. The pooled multivariate RRs comparing the highest vs lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95% CI, 0.90-1.11) for colon cancer and 0.85 (95% CI, 0.72-1.01) for rectal cancer (P for common effects by tumor site = .07). CONCLUSIONS: In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer.
Colorectal Neoplasms↗
Genetic variation in the HSD17B1 gene and risk of prostate cancer.
Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites.
17-Hydroxysteroid Dehydrogenases↗
Frequency and predictors of inappropriate management of recurrent gout attacks in a longitudinal study.
OBJECTIVE: To evaluate the patterns and determinants of medication use during recurrent gout attacks. METHODS: We followed participants with documented gout in an online prospective case-crossover study. During an attack, subjects were asked if they had consulted a physician for the attack and what medications they were using. Definitely inappropriate therapy was defined as use of allopurinol or a uricosuric agent acutely without having used it as a prophylactic. Potentially inappropriate therapy was defined as use of analgesics alone, alternative remedies, or no medications. We estimated the risk of having >or= 1 attack in 1 year using life table methods. We examined the relation of various risk factors to the risk of inappropriate therapy using Poisson regression. RESULTS: Among 232 participants (mean age 52 yrs, 81% male) with documented gout, the risk of having >or= 1 attack in a year was 69%. One hundred ten participants consulted a physician for each attack, 49 did so for only some attacks, while 43 never consulted a physician for any attack. Fifty-three participants had definitely (n = 10) or potentially (n = 43) inappropriate therapy for their recurrent attacks. Physician consultation for an attack was associated with increased risk of inappropriate therapy (risk ratio, RR, 2.5, p = 0.006), whereas an increasing number of gout attacks was associated with lower risk of inappropriate therapy (RR 0.8, p = 0.01). CONCLUSION: Given the high risk of recurrent attacks and the substantial number of persons whose attacks are not appropriately managed, further education about management of gout attacks for both patients and physicians may be warranted.
Adult↗
Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania.
OBJECTIVES: To examine the association of anemia with mortality and disease progression among a cohort of women with HIV in Dar es Salaam, Tanzania. METHODS: Time to all-cause death, AIDS-related death, and a 50% decrease in CD4 cell count among 1078 HIV-positive pregnant women enrolled in a clinical trial of vitamin supplementation from 1995-2003. RESULTS: Adjusted models showed that anemia was associated with an increased risk of all-cause mortality (relative hazard [RH]: 2.06, 95% CI: 1.52 to 2.79 for moderate anemia and RH: 3.19, 95% CI: 2.23 to 4.56 for severe anemia) and AIDS-related mortality (RH: 2.21, 95% CI: 1.53 to 3.19 for moderate anemia and RH: 3.47, 95% CI: 2.25 to 5.33 for severe anemia), independent of CD4 cell count, World Health Organization clinical stage, age, pregnancy, vitamin supplementation, and body mass index. Anemia was also associated with a more rapid decline in CD4 counts, measured as time to a 50% drop in CD4 cell count from baseline. Erythrocyte characteristics suggestive of iron deficiency were also associated with all-cause and AIDS-related death and a 50% decline in CD4 cell count. CONCLUSIONS: Anemia is an independent predictor of mortality and disease progression in this cohort. Screening for anemia, coupled with prevention and treatment efforts, should be included in HIV care initiatives, particularly those that target women.
Anemia↗
Moving upstream or muddying the waters? Incentives for managing for health.
OBJECTIVES: The objective of this study was to identify factors influencing the capacity of NHS managers to 'manage for health'. STUDY DESIGN: Semi-structured interviews (32) were carried out over the telephone or face to face with national stakeholders (15) and NHS senior managers (17) from four Strategic Health Authorities (SHAs) and five Primary Care Trusts (PCTs) in England. Interviews were transcribed and a qualitative analysis carried out. RESULTS: The current system of targets and incentives prioritised access to acute services, public health skills were too thinly spread, baseline data were inadequate, decision-making for public health investment was fragmented and evidence for effective interventions was scanty. Health improvement targets should be plausible, longer term and locally owned, but key factors in creating a proactive public health organisation were a strong public health ethos, and effective management and leadership skills. Strengthening the NHS's role in managing for health was welcomed, but enthusiasm was tempered by concurrent NHS policy initiatives and incentives pulling in opposing directions. CONCLUSIONS: Key NHS policy initiatives have been developed in isolation from each other. While their combined effect remains unpredictable, they may serve to threaten the welcome shift towards managing for health improvement.
Health Status↗
CYP19 (aromatase) haplotypes and endometrial cancer risk.
Endogenous estrogen exposure is an important determinant of endometrial cancer risk. Aromatase, encoded by CYP19, catalyzes the aromatization of androstenedione and testosterone to estrone and estradiol, respectively. Several common genetic polymorphisms in CYP19 have been identified, including a TCT insertion/deletion and a (TTTA)(n) repeat polymorphism in intron IV as well as a 3'UTR C/T polymorphism. We evaluated these 3 polymorphisms plus an additional 9 noncoding polymorphisms as individual genotypes and predicted haplotypes as risk factors for endometrial cancer using a nested case-control study design. Invasive endometrial cancer cases (n = 222) and matched controls (n = 666) were identified among participants in the Nurses' Health Study who had provided a blood sample in 1989-1990 (n = 32,826). We estimated haplotypes from unphased genotype data spanning > 123 kb of CYP19. Six haplotypes constructed from 10 SNPs were estimated with a frequency > or = 5%. The highest prevalence haplotype (33% among cases, 28% among controls) was significantly associated with endometrial cancer risk (p = 0.03). Loci with variant alleles that comprise the risk haplotype were independently associated with endometrial cancer, with relative risk estimates ranging from 1.68 (95% CI 1.13-2.48) to 2.07 (95% CI 1.33-3.23), comparing variant allele carriers to wild-type homozygotes. We observed significant interactions between menopausal status and 2 of the high-risk loci (p = 0.03 and p < 0.01), with > 2-fold increased risk for variant allele carriers who were postmenopausal but no association between genotype and endometrial cancer among premenopausal women. We evaluated associations between CYP19 haplotypes and plasma steroid hormone levels. The haplotype associated with endometrial cancer risk is also significantly associated with the ratios of estrone to androstenedione and estradiol to testosterone, the products and substrates of the enzyme aromatase, encoded by CYP19. Our data suggest that there is a high-frequency CYP19 haplotype related to higher estrogen to androgen ratios and increased risk of endometrial cancer and that this association may primarily pertain to postmenopausal women.
Adult↗
Dietary patterns and the risk of postmenopausal breast cancer.
The association between individual foods and breast cancer has been inconsistent. Therefore, we examined the association between diet and risk of postmenopausal breast cancer by the alternative approach of dietary patterns. Dietary patterns were identified with factor analysis from food consumption data collected from a food frequency questionnaire in 1984. Relative risks were computed using proportional hazard models and adjusted for known risk factors for breast cancer. Between 1984 and 2000, we ascertained 3,026 incident cases of postmenopausal breast cancer. We identified 2 major dietary patterns. The prudent pattern is characterized by higher intake of fruits, vegetables, whole grains, low-fat dairy products, fish and poultry, while the Western pattern is characterized by higher intake of red and processed meats, refined grains, sweets and desserts and high-fat dairy products. Neither of the patterns was associated with overall risk of postmenopausal breast cancer. However, a positive association between the Western pattern score was observed among smokers at baseline (relative risk = 1.44, comparing top to bottom quintiles; 95% CI = 1.02-2.03; p for trend = 0.03). An inverse association was observed between the prudent pattern and estrogen receptor-negative cancer (relative risk = 0.62; 95% CI = 0.45-0.88; p for trend = 0.006). Among the major food groups, higher consumptions of fruits (relative risk for 1 serving/day increase = 0.88; 95% CI = 0.80-0.97; p = 0.009) and vegetables (relative risk = 0.94; 95% CI = 0.88-0.99; p = 0.03) were significantly associated with decreased risk for ER(-) breast cancer. In conclusion, we did not observe an overall association between the prudent or Western pattern and overall breast cancer risk. However, a Western-type diet may elevate risk of breast cancer among smokers, and a prudent diet may protect against estrogen receptive-negative tumors.
Breast Neoplasms↗
Prospective study of N-acetyltransferase-2 genotypes, meat intake, smoking and risk of colorectal cancer.
Consumption of red meat has been associated with elevated risk of colorectal cancer; however, mechanisms underlying this relationship are not well established. N-acetyltransferase 2 (NAT2) appears to activate carcinogenic heterocyclic amines found in meat as well as cigarette smoke. Genetic variation in this enzyme, associated with rapid acetylation, may modulate the influence of meat intake on cancer risk. We examined the risk of incident colorectal cancer according to NAT2 genotypes, meat intake and smoking in a prospective, nested case-control study among 32,826 women enrolled in the Nurses' Health Study who provided prediagnostic blood specimens. We matched 183 women with colorectal cancer to 443 controls. Although acetylator genotype alone was not associated with the risk of colorectal cancer, women with rapid acetylator genotypes experienced a greater risk associated with intake of > or = 0.5 serving of beef, pork or lamb as a main dish per day compared to intake of less meat (multivariate OR = 3.01; 95% CI = 1.10-8.18). In contrast, among slow acetylators, intake of beef, pork or lamb was not associated with risk of colorectal cancer (multivariate OR = 0.87; 95% CI = 0.35-2.17). The interaction between acetylator genotype and meat intake approached statistical significance (P interaction = 0.07). Moreover, compared to slow acetylators who smoked < or = 35 pack-years and ate < 0.5 serving/day of red meat, the OR for rapid acetylators who smoked > 35 pack-years and ate > or = 0.5 serving/day was 17.6 (95% CI 2.0-158.3). These prospective data suggest that red meat may increase the risk of colorectal cancer, particularly among genetically susceptible individuals. The influence of NAT2 genotype on this association supports a role for heterocyclic amines in mediating the effect of red meat on colorectal carcinogenesis.
Adult↗
Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women.
BACKGROUND: Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis, but human data for this role have been conflicting, possibly because of problems related to study design or measurement of iron exposure. We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospective, nested case-control study of women enrolled in the Nurses' Health Study. METHODS: Among 32 826 women who provided a blood specimen, we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection. We assessed iron intake, mutations in the HFE gene that are associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma biochemical measures of total body iron, including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin. Logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). All statistical tests were two-sided. RESULTS: Women with any HFE gene mutation had higher total body iron stores, as reflected by higher transferrin saturations (P < .001) and lower levels of the ratio of transferrin receptors to ferritin (P = .02), than women with no HFE gene mutation. However, HFE gene mutations were not associated with risk of adenoma (multivariable RR = 1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation (multivariable RR = 0.96, 95% CI = 0.63 to 1.47; Ptrend = .66), the ratio of transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60; Ptrend = .99), or dietary iron intake (multivariable RR = 1.04, 95% CI = 0.68 to 1.57; Ptrend = .94). CONCLUSIONS: Although our study used several distinct measures of iron status (i.e., genetic mutations, biochemical markers, and dietary intake) and a nested case-control design, we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women.
Adenoma↗