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PDF - 41KB, Characteristics of Study Population.

Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type.Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site.Results: The five polymorphisms were not associated with ovarian carcinoma overall (Ptrend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; Pheterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05).Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification.Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology. Cancer Epidemiol Biomarkers Prev; 19(7); 1822–30. ©2010 AACR.

Background: Recent findings suggest that alcohol consumption may reduce risk of multiple myeloma.Methods: To better understand this relationship, we conducted an analysis of six case–control studies participating in the International Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary ORs and 95% confidence intervals (CI) relating different measures of alcohol consumption and multiple myeloma risk were computed by unconditional logistic regression with adjustment for age, race, and study center.Results: Cases were significantly less likely than controls to report ever drinking alcohol (men: OR = 0.72; 95% CI, 0.59–0.89; women: OR = 0.81; 95% CI, 0.68–0.95). The inverse association with multiple myeloma was stronger when comparing current to never drinkers (men: OR = 0.57; 95% CI, 0.45–0.72; women: OR = 0.55; 95% CI, 0.45–0.68), but null among former drinkers. We did not observe an exposure–response relationship with increasing alcohol frequency, duration, or cumulative lifetime consumption. Additional adjustment for body mass index, education, or smoking did not affect our results; and the patterns of association were similar for each type of alcohol beverage examined.Conclusions: Our study is, to our knowledge, the largest of its kind to date, and our findings suggest that alcohol consumption may be associated with reduced risk of multiple myeloma.Impact: Prospective studies, especially those conducted as pooled analyses with large sample sizes, are needed to confirm our findings and further explore whether alcohol consumption provides true biologic protection against this rare, highly fatal malignancy. Cancer Epidemiol Biomarkers Prev; 22(9); 1620–7. ©2013 AACR.

Supplementary Tables S1-S6, Supplementary References. Supplementary Table S1. Characteristics of included studies; S2. Complete-case analysis of ten years estimated hazard ratios (HR) for all cause death in patients with ovarian cancer. S3. Complete-case analysis of ten years estimated subhazard ratios (SHR) for ovarian cancer death in patients with ovarian cancer. S4. Ten years estimated subhazard ratios (SHR) for ovarian cancer death in patients with ovarian cancer (with multiple imputation for missing grade and stage). S5. Complete-case analysis of ten years estimated hazard ratios (HR) for all cause death in patients with high grade serous ovarian cancer. S6. Ten years estimated hazard ratios (HR) for all cause death in patients with high grade serous ovarian cancer (with multiple imputation for missing stage).

Supplementary Tables 1-2 from Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium

PDF - 8738K, Figure S1 H&E staining from three high-grade serous (A, B, C) and three endometrioid carcinomas (D, E, F)

PDF - 53KB, Risk of Multiple Myeloma associated with alcohol consumption in pooled study population by ever and former drinkers.

PDF - 64KB, Risk of Multiple Myeloma associated with beer, wine, liquor consumption in pooled study population by gender.

PDF - 59K, Legend for Supplementary Figure 1.

Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case–control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI.Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls.Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04–1.14; P = 0.007]. We observed significant heterogeneity by study design (P = 0.04), noting the BMI–multiple myeloma association only for population-based studies (Ptrend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m2; OR, 1.2; 95% CI, 1.1–1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI (Pinteraction 2) or obese (30+ kg/m2) in both younger and usual adulthood (vs. individuals consistently 2), but not for those overweight or obese at only one time period.Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood.Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876–85. ©2017 AACR.

Table S1. Characteristics of the case-control studies included in the International Multiple Myeloma Consortium (IMMC) Lifestyle Factors Pooling Project (LFPP). Table S2. Usual adult BMI and pooled relative risk of multiple myeloma in population-based case-control studies within category of selected demographic risk factors. Table S3. Usual adult BMI and pooled relative risk of multiple myeloma in hospital-based case-control studies within category of selected demographic risk factors. Table S4. Pooled relative risk of multiple myeloma by category of weight and height: overall and by study design and interview type.

PDF - 100K, Table S1 Demographics from the OTTA cohorts representing the test set and excluded cases Table S2 Antibodies, details of immunohistochemical protocols and scoring cut-off Table S3 Training set revision of the COSP model - Areas under the curve (AUC) by histology and model Table S4 Test for heterogeneity for marker expression between training and testing set Table S5 Pairwise agreement of histological types in the testing set by classification method for A_COSP Table S6 Univariate Cox model in the testing set comparing A_COPS and TB_COSPv2. Table S7 Five-year survival estimates for four different type assignments as defined in the text within histological types Table S8 Demographics of endometrioid carcinomas in the test set classified by different methods Table S9 Prediction of type in test set among cases with unclear original diagnosis (N=71).

Supplementary Figure 2 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer

Supplementary Figure 3 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer

Supplementary Materials, Legends for Figures 1-5 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer

A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P < 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.

PDF file - 145K, Supplementary Table 1. Studies in the Ovarian Cancer Association Consortium (OCAC) are listed, as well as the abbreviation, location, type, and number of cases and controls for each study. Supplementary Table 2. The number of cases included in the analysis from each OCAC study site is listed by histologic subtype. Supplementary Table 3. Gene symbols and IDs are listed for NF-κB pathway genes that were tagged in this study, as well as chromosome position, number of SNPs tagged, and bin coverage of each gene using Hapmap or 1000 genomes as a reference. Supplementary Table 4. Reasons and numbers of samples excluded from the analysis following the sample quality control are described. Supplementary Table 5. We evaluated rs17561 and rs6785617 for interactions with known epidemiologic risk factors for risk of clear cell and LMP tumors, respectively, and report interaction p-values in the table below.

Supplementary Figure 4 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer

Supplementary Figure 1 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer

Supplementary Figure 5 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer

It has been reported that levo-1-methyl tryptophan (L-1MT) can block indoleamine-2,3-dioxygenase (IDO) expressed by human dendritic cells (DC), whereas dextro-1-methyl tryptophan (D-1MT) is inefficient. However, whether L-1MT or D-1MT can efficiently reverse IDO-induced arrest of human T-cell proliferation has not been clarified. Here, we show a marked immunosuppressive effect of IDO derived from INDO-transfected 293 cell, IDO+ ovarian cancer cells, and monocyte-derived DCs on CD4+ Th1 cells, CD8+ T cells, and natural killer cells derived from peripheral blood, ascites, and tumors of ovarian cancer patients. We found that, whereas L-1MT and D/L-1MT can restore proliferation of tumor-derived and peripheral blood T-cell subsets, D-1MT does not effectively restore IDO-induced arrest of T-cell proliferation. Although D-1MT inhibited kynurenine production at high concentrations, L-1MT was more effective in abrogating kynurenine generation and tryptophan depletion, whereas tryptophan was completely depleted by IDO even in the presence of high amounts of D-1MT. Together, the results indicate that, whereas the generation of tryptophan metabolites (kynurenines) by IDO is important in mediating suppression of T-cell proliferation, the degree to which tryptophan depletion is restored by 1MT is also critical in overcoming IDO-induced arrest of T-cell proliferation. [Cancer Res 2009;69(13):5498–504]

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p

While BRCA1 and BRCA2 mutations are known to confer the largest risk of breast cancer and ovarian cancer, the incomplete penetrance of the mutations and the substantial variability in age at cancer onset among carriers suggest additional factors modifying the risk of cancer in BRCA1/2 mutation carriers. To identify genetic modifiers of BRCA1/2, we carried out a whole-genome sequencing study of 66 ovarian cancer patients that were enriched with BRCA carriers, followed by validation using data from the Pan-Cancer Analysis of Whole Genomes Consortium. We found PPARGC1A, a master regulator of mitochondrial biogenesis and function, to be highly mutated in BRCA carriers, and patients with both PPARGC1A and BRCA1/2 mutations were diagnosed with breast or ovarian cancer at significantly younger ages, while the mutation status of each gene alone did not significantly associate with age of onset. Our study suggests PPARGC1A as a possible BRCA modifier gene. Upon further validation, this finding can help improve cancer risk prediction and provide personalized preventive care for BRCA carriers.

Objective:\ud We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries.\ud \ud Subjects and Methods:\ud The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared.\ud \ud Results:\ud The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (

Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance.We carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy.We found seven SNPs at 12q24.33 associated with PFS (The locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer.This finding provides insight into genetic markers associated with EOC outcome and potential treatment options.

The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes.We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics.The ORs associated for high-grade serous ovarian cancer were 3.01 forWe have found strong evidence that carriers of

Our objective was to determine whether the frequencies of non-ovarian cancers (NOC) within families in a large Familial Ovarian Cancer Registry (FOCR) are significantly different from the frequencies listed in the SEER database. The FOCR was established in 1981. Registry members are families with two or more first degree relatives who have a diagnosis of ovarian cancer, three or more cases of cancer on one side of the family with at least one being ovarian, at least one female with two or more primary cancers in which one is ovary, or a history of two or more cancers in the family with at least one being ovarian cancer diagnosed before the age of 45. The data was analyzed to find relative rates of 10 of the most common cancers found within the database, with the exception of ovarian and breast. These include bladder, CNS, cervical, colorectal, liver, lung, pancreas, prostate, stomach, and uterine. Cancers were further stratified by age at diagnosis, and compared to information in the SEER database. There are 2,671 pedigrees and a total of 50,454 individuals within the FOCR. There are 1,938 families with two or more relatives with ovarian cancer, accounting for 4,816 individuals with ovarian cancer. The total number of individuals with ovarian cancer is 5,421. Of these individuals with ovarian cancer, 2,249 have been verified with testing or physician correspondence. The frequencies of the NOCs within the registry were higher than that of the general population as described in the SEER database. In particular, the overall frequencies of cancers of the bladder, cervix, prostate, and uterus were higher within the FOCR at 2.3, 7.4, 25.2, and 11.9 per 1,000 respectively. Furthermore, diagnoses of both cervical and uterine cancers tended to occur at an earlier age within the FOCR. The overall frequencies of cancers of the bladder, cervix, prostate, and uterus are higher in the FOCR compared with a general population database. Future studies on segregation analysis and genome-wide linkage studies are warranted on families with NOC within the Familial Ovarian Cancer Registry.

Serum lipid levels are major risk factors for cardiovascular disease. In addition to diet, exercise, genetics, age and race, serum concentrations of persistent organic pollutants (POPs) influence concentrations of serum lipids. We investigated associations between fasting concentrations of 35 polychlorinated biphenyl (PCB) congeners and nine organochlorine pesticides in relation to total serum lipids, total cholesterol, low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides in 525 Caucasian and African American residents of Anniston, Alabama, who were not on any lipid-lowering medication. In Model 1, data were adjusted for age, age quadratic, gender, BMI, alcohol consumption, smoking and exercise, while in Model 2, additional adjustment was done for other POPs. As compared to Caucasians, African Americans had lower levels of total lipids and triglycerides with higher concentrations of HDL cholesterol, but higher concentrations of PCBs and pesticides. Total pesticides were more strongly associated with elevations in serum lipids than were total PCBs, and the associations were stronger in African Americans. Total DDTs were not associated with serum lipids after adjustment for other POPs in either racial group, while the strongest positive associations were seen for hexachlorobenzene (HCB) in both racial groups. Racial differences in lipid profiles, concentrations of POPs and associations between POP concentrations and serum lipids are relevant to racial differences in rates of cardiovascular disease. Keywords: PCBs, Pesticides, Cardiovascular disease, Cholesterol, Triglycerides, HDL

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

Experimental studies suggest that dioxin-like compounds influence thyroid function, although human studies have presented equivocal results. Great Lakes sportfish consumers represent a population with greater potential for exposure to dioxin-like compounds than non-consumers. Thirty-eight licensed anglers participating in a dioxin exposure study, consumers and non-consumers, conducted as part of the New York Angler Cohort Study, donated blood and completed questionnaires regarding demographic, clinical, and sportfish consumption data. Sera were analyzed for polychlorinated dibenzo- p -dioxins (PCDDs), dibenzofurans (PCDFs), coplanar biphenyls (PCB), and PCB IUPAC #153, in addition to thyroid stimulating hormone (TSH), total and free thyroxine (T 4 and fT 4 ), total triiodothyronine (T 3 ), and lipids. An inverse linear association between serum fT 4 and the sum of dioxin-like congener concentrations (∑DIOXs) in serum ( B = −0.3, 95% CI = −0.5, −0.1) was identified adjusting for PCB #153 and serum lipids ( R 2 = 0.3, p = 0.02, n = 37). The results of this study are preliminary but suggest an inverse association between dioxin-like compounds and fT 4 .

Lifetime lactation in relation to breast cancer risk was examined in a case-control study in two counties in western New York. Cases were women age 40 years and over with incident, primary, histologically confirmed breast cancer. Controls were age- and county-frequency matched, selected from New York State driver's license records (for those less than age 65 years) and from Health Care Finance Administration Records (for those age 65 or more). Included were women with at least one livebirth (253 premenopausal and 367 postmenopausal cases and 266 premenopausal and 427 postmenopausal controls). Breast cancer risk was very weakly associated with long duration of lactation among premenopausal women; the odds ratio for at least 20 months lifetime lactation was 0.50 (95% confidence interval 0.21-1.12). Among postmenopausal women, the protective effect of lactation was restricted to women with first lactation before age 25 years (odds ratio = 0.67, 95% confidence interval 0.46-0.95). However, age at first birth was highly correlated with age at first lactation. Neither insufficient milk as a reason for not breastfeeding nor having received medication to stop milk flow was associated with increased risk. These findings are in accordance with accumulating evidence that lactation may have a weak protective effect on breast cancer risk.

This postdoctoral research fellowship included a thorough investigation of genetic and environmental determinants of breast cancer risk. Major findings from this research include the following: (1) smoking may be an important risk factor for breast cancer among postmenopausal women with genetically-determined slow acetylation phenotype; (2) the null GSTM1 genotype may be associated with breast cancer risk among premenopausal smokers, but is not an overall risk factor for breast cancer; (3) the CYP1A1 variant genotype is not a strong risk factor for breast cancer, but may be associated with greater risk among smokers; (4) consumption of processed meats, high sources of known mammary mutagens, may increase risk for premenopausal breast cancer, particularly among women with rapid NAT2 genotype; (5) the CYP2E1 variant genotype is not associated with risk, but may be a risk factor for premenopausal smokers; (6) higher serum organochlorine levels were not associated with greater risk of postmenopausal breast cancer; (7) higher serum levels of PCBs were associated with increased risk of breast cancer among parous women who never lactated; and (8) the CYP1A1 variant genotype was a risk factor for women with high PCB body burden. Methodological issues concerning the investigation of organochlorine compounds in epidemiologic studies were explored.

Risk of multiple myeloma (MM), a highly fatal cancer, is increased in older age, men, African Americans, and persons with monoclonal gammopathy of undetermined significance (MGUS). Modifiable risk factors for MM remain obscure. Tobacco and alcohol use findings are inconsistent. To further assess the etiologic role of these lifestyle factors, the International Multiple Myeloma Consortium (IMMC) pooled individual-level questionnaire data from 6 case-control studies with alcohol data (n: cases=1,484, controls=6,542) and 9 case-control studies with smoking data (n: cases=2,662, controls=11,890). A pooled multivariable logistic regression analysis using a random effects model and adjusting for age, race, and study center location showed a decreased MM risk among men who reported ever drinking alcohol regularly compared with non-drinkers [odds ratio (OR) 0.71, 95% confidence interval (CI) 0.57–0.87], while results among women were null (OR 0.98, 0.76–1.26). Frequency, duration, and cumulative lifetime consumption of alcohol use were not linearly associated with MM risk among men or women. Neither a history of cigarette smoking compared to never smokers, nor any quantification of dose or duration of smoking was associated with MM risk in the pooled study population. Our findings are very similar to those reported from a pooled analysis of smoking and alcohol use conducted among case-control studies of non-Hodgkin lymphoma, a collection of lymphoid malignancies that are predominatly B-cell in origin, like MM (1, 2). Prospective studies may provide further insight into the association between alcoholic beverage consumption and MM risk. References: 1. Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS, Stagnaro E, Willett EV, Dal Maso L, Serraino D, Chang ET, Cozen W, Davis S, Severson RK, Bernstein L, Mayne ST, Dee FR, Cerhan JR, Hartge P; InterLymph Consortium. Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis. Lancet Oncol 2005;6:469–76. 2. Morton LM, Hartge P, Holford TR, Holly EA, Chiu BC, Vineis P, Stagnaro E, Willett EV, Franceschi S, La Vecchia C, Hughes AM, Cozen W, Davis S, Severson RK, Bernstein L, Mayne ST, Dee FR, Cerhan JR, Zheng T. Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph). Cancer Epidemiol Biomarkers Prev 2005;14:925–33. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B115.