Scientific Highlights

ALL CANCERS

Dairy Food and Calcium Intake

Dairy food and calcium intake in relation to total cancer and cancer at individual sites was examined in the NIH-AARP Diet and Health Study. During an average of seven years of follow-up, 36,965 and 16,605 cancer cases in men and women, respectively, were identified. Calcium intake was not related to total cancer in men but was nonlinearly associated with total cancer in women; the risk decreased up to approximately 1,300 mg/d, above which no further risk reduction was observed (see Figure 1). In men and women, dairy food and calcium intakes were inversely associated with cancers of the digestive system, particularly for colorectal cancer. (Park Y, Leitzmann MF, Subar AF, Hollenbeck A, Schatzkin A. Dairy food, calcium, and risk of cancer in the NIH-AARP Diet and Health Study. Arch Intern Med 2009;169:391−401)

Occupational Exposure to Heterocyclic Aromatic Amine Pesticides

Cancer incidence was evaluated among 20,646 imazethapyr-exposed pesticide applicators enrolled in the Agricultural Health Study, a prospective cohort of 57,311 licensed pesticide applicators enrolled from 1993 to 1997. A total of 2,907 incident cancers developed through 2004. The authors found significant trends in risk with increasing lifetime exposure days for bladder cancer and colon cancer. Rate ratios increased by 137% for bladder cancer and 78% for colon cancer when those with highest exposure were compared to the nonexposed. The excess risk for colon cancer was limited to proximal cancers (rate ratio = 2.7). (Koutros S, Lynch CF, Ma X, Lee WJ, Hoppin JA, Christensen CH, Andreotti G, Freeman LB, Rusiecki JA, Hou L, Sandler DP, Alavanja MC. Heterocyclic aromatic amine pesticide use and human cancer risk: Results from the U.S. Agricultural Health Study. Int J Cancer 2009;124:1206−1212)

Risks by Type of Meat Intake

This study assessed the relationships of red, white, and processed meat intakes to risk for total and cause-specific mortality in the NIH-AARP Diet and Health Study. There were 47,976 male deaths and 23,276 female deaths during 10 years of follow-up. Men and women in the highest vs. lowest quintile of red (hazard ratio [HR] = 1.31 and 1.36, respectively) and processed meat (HR = 1.16 and 1.25, respectively) intakes had elevated risks for overall mortality. Men and women had elevated risks for cancer mortality for red (HR = 1.22 and 1.20, respectively) and processed meat (HR = 1.12 and 1.11, respectively) intakes and for cardiovascular disease mortality for red (HR = 1.27 and 1.50, respectively) and processed meat (HR = 1.09 and 1.38, respectively) intakes. When comparing the highest with the lowest quintile of white meat intake, there was an inverse association for total mortality and cancer mortality as well as for all other deaths for men and women. (Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin A. Meat intake and mortality: A prospective study of over half a million people. Arch Intern Med 2009;169:562−571)

 

BREAST CANCER

Two New Risk Alleles Identified

A three-stage genome-wide association study (GWAS) of breast cancer was conducted among 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility initiative. In stage one, 528,173 single nucleotide polymorphisms (SNPs) in 1,145 cases of invasive breast cancer and 1,142 controls were genotyped. In stage two, 24,909 top SNPs in 4,547 cases and 4,434 controls were analyzed. In stage three, the authors investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433) resides in a large linkage disequilibrium block neighboring NOTCH2 and FCGR1B; this signal was stronger for estrogen receptor–positive tumors. A second SNP on chromosome 14q24.1 (rs999737) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. Associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26, and 16q12.1 were also confirmed. (Thomas G, Jacobs KB, Kraft P, Yeager M, Wacholder S, Cox DG, Hankinson SE, Hutchinson A, Wang Z, Yu K, Chatterjee N, Garcia-Closas M, Gonzalez-Bosquet J, Prokunina-Olsson L, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver R, Prentice R, Jackson R, Kooperberg C, Chlebowski R, Lissowska J, Peplonska B, Brinton LA, Sigurdson A, Doody M, Bhatti P, Alexander BH, Buring J, Lee IM, Vatten LJ, Hveem K, Kumle M, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Chanock SJ, Hunter DJ. A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet 2009;41:579−584)  

 

CERVICAL CANCER

Human Papillomavirus Type and Precancerous Lesions

The authors investigated the timing of diagnosis of histologic cervical intraepithelial neoplasia grade 3 or worse (CIN3+) using data from the Atypical Squamous Cells of Undetermined Significance–Low-grade Squamous Intraepithelial Lesion Triage Study. Among women who were positive for human papillomavirus type 16 (HPV-16) at enrollment, 85% of CIN3+ were diagnosed at enrollment, compared with 57% and 58%, respectively, in women who were HPV-18/45 positive and other carcinogenic type–positive at enrollment. In contrast, among women who were HPV-16 positive at enrollment, only 7% of CIN3+ were diagnosed at study exit, compared with 31% and 21%, respectively, of CIN3+ diagnosed at study exit in women who were HPV-18/45 positive and other carcinogenic type–positive at enrollment. Results also indicate an underrepresentation of HPV-18/45 in precancers; whether this is due to occult pathology needs further investigation. (Safaeian M, Schiffman M, Gage J, Solomon D, Wheeler CM, Castle PE. Detection of precancerous cervical lesions is differential by human papillomavirus type. Cancer Res 2009;69:3262−3266)

 

ESOPHAGEAL AND GASTRIC CANCERS

Nutrient Supplementation

In a randomized cancer prevention trial conducted in Linxian, China, in which 29,584 adults were given daily vitamin and mineral supplements, treatment with “factor D”—a combination of 50 µg selenium, 30 mg vitamin E, and 15 mg beta-carotene—led to decreased mortality from all causes, cancer overall, and gastric cancer. Participants who received factor D had lower overall mortality (HR = 0.95; a reduction in cumulative mortality from 33.62% to 32.19%), and gastric cancer mortality (HR = 0.89; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Factor D did not affect esophageal cancer mortality overall; however, this outcome decreased 17% among participants younger than 55 years (HR = 0.83) but increased 14% among those aged 55 years or older (HR = 1.14). Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation was associated with decreased stroke mortality. (Qiao YL, Dawsey SM, Kamangar F, Fan JH, Abnet CC, Sun XD, Johnson LL, Gail MH, Dong ZW, Yu B, Mark SD, Taylor PR. Total and cancer mortality after supplementation with vitamins and minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial. J Natl Cancer Inst 2009;101:507−518)

Nonsteroidal Anti-inflammatory Drug Use

The association between self-reported use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) in the past 12 months and gastric noncardia (n = 182), gastric cardia (n = 178), and esophageal adenocarcinomas (n = 228) was examined in a prospective cohort (n = 311,115) followed for seven years. Use of aspirin (HR = 0.64) or other NSAIDs (HR = 0.68) was associated with a lower risk of gastric non-cardia adenocarcinoma. No significant associations were found for either aspirin or other NSAIDs with gastric cardia cancer or esophageal adenocarcinoma. In a meta-analysis, aspirin or NSAID use was inversely associated with gastric and esophageal adenocarcinomas. (Abnet CC, Freedman ND, Kamangar F, Leitzmann MF, Hollenbeck AR, Schatzkin A. Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: Results from a cohort study and a meta-analysis. Br J Cancer 2009;100:551−557)

Physical Activity

This study investigated the association between physical activity and esophageal and gastric carcinoma among 487,732 U.S. men and women in the NIH-AARP Diet and Health Study. Among 523 cases of esophageal carcinoma (149 squamous cell and 374 adenocarcinoma) and 642 cases of gastric carcinoma (313 cardia and 329 noncardia), physical activity was associated with reduced risk of combined esophageal and gastric adenocarcinomas but was unrelated to esophageal squamous cell carcinoma (ESCC). The inverse association with physical activity was strongest for gastric noncardia adenocarcinoma (relative risk [RR] for highest vs. lowest physical activity level = 0.62). Relationships were weaker and not significant for gastric cardia adenocarcinoma (RR = 0.83) and esophageal adenocarcinoma (RR = 0.75). No significant relationship with physical activity was observed for ESCC. (Leitzmann MF, Koebnick C, Freedman ND, Park Y, Ballard-Barbash R, Hollenbeck A, Schatzkin A, Abnet CC. Physical activity and esophageal and gastric carcinoma in a large prospective study. Am J Prev Med. 2009;36:112−119)

Telomeres and Chromosome Instability

The association between genome-wide chromosomal changes in cancer cells and telomere length/attrition in cancer/stroma cells was investigated in 47 ESCC patients. Telomere length differed significantly among cell types, such that length in infiltrative lymphocytes was greater than length of carcinoma-associated fibroblasts (CAFs), which were longer than cancer cells. Shortened telomeres were observed in cancer cells in 94% of the tumors examined. Telomere length in CAFs was significantly associated with chromosomal instability on 4q and 13q, and lymphocyte telomere length was significantly associated with instability on chromosomal arm 15q. Telomere attrition in cancer cells, defined as the telomere length in CAFs minus the telomere length in cancer cells, was significantly associated with chromosomal instability on 13q and 15q. (Zheng YL, Hu N, Sun Q, Wang C, Taylor PR. Telomere attrition in cancer cells and telomere length in tumor stroma cells predict chromosome instability in esophageal squamous cell carcinoma: A genome-wide analysis. Cancer Res 2009;69:1604−1614)

 

GENETICS

Genome-wide and Candidate Gene Study of Smoking Behaviors

The contribution of genetic variation to smoking behaviors was investigated in a joint analysis of two GWAS in 2,329 men from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and 2,282 women from the Nurses’ Health Study. Seven measures of smoking behavior, four continuous (cigarettes per day [CPD], age at initiation of smoking, duration of smoking, and pack years) and three binary (ever vs. never smoking, ≤ 10 vs. > 10 cigarettes per day [CPDBI], and current vs. former smoking) were analyzed. None of the SNPs achieved genome-wide significance (p < 10-7) in any combined analysis pooling evidence across the two studies; between two and seven SNPs with p < 10-5 for each of the seven measures were observed. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, multiple SNPs associated with CPD (p < 10-3) were identified, including rs1051730, which has been associated with nicotine dependence, smoking intensity, and lung cancer risk. The authors also selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual gene and gene-group analyses. Between two and five genes associated with each measure of smoking behavior were identified. Aside from CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p < 5.4 x 10-5). (Caporaso N, Gu F, Chatterjee N, Sheng-Chih J, Yu K, Yeager M, Chen C, Jacobs K, Wheeler W, Landi MT, Ziegler RG, Hunter DJ, Chanock S, Hankinson S, Kraft P, Bergen AW. Genome-wide and candidate gene association study of cigarette smoking behaviors. PLoS ONE 2009;4:e4653)

Mortality in Retinoblastoma Survivors

The authors examined cause-specific mortality among retinoblastoma survivors diagnosed between 1914 and 1996 at two U.S. institutions. A total of 151 deaths due to subsequent malignant neoplasms occurred among 1,092 hereditary retinoblastoma survivors (standardized mortality ratio [SMR] = 35) compared with 12 deaths among 762 nonhereditary retinoblastoma survivors (SMR = 2.5). Excess mortality from subsequent malignant neoplasms (particularly sarcomas, melanomas, and cancers of the brain and other parts of the nervous system) among hereditary retinoblastoma survivors extended beyond 40 years after retinoblastoma diagnosis. Elevated risk of death from lung cancer among hereditary retinoblastoma survivors was also confirmed. Relative rates of mortality from subsequent malignant neoplasms were higher among those who had been treated with radiotherapy than among those who had not. Cumulative mortality from subsequent malignant neoplasms at 50 years after retinoblastoma diagnosis was 25.5% for hereditary retinoblastoma survivors and 1.0% for nonhereditary retinoblastoma survivors (see Figure 2). (Yu CL, Tucker MA, Abramson DH, Furukawa K, Seddon JM, Stovall M, Fraumeni JF Jr, Kleinerman RA. Cause-specific mortality in long-term survivors of retinoblastoma. J Natl Cancer Inst 2009;101:581−591)

 

HEAD AND NECK CANCERS

Risks Associated with Alcohol Type

The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate associations with beverage consumption for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls) using never drinkers of alcohol (1,124 cases, 3,487 controls) as a common reference group. They observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios [ORs] = 1.6, 1.9, 2.2, and 5.4 for ≤ 5, 6–15, 16–30, and > 30 drinks per week, respectively) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6). Among wine-only drinkers, the ORs for moderate levels of consumption frequency approached the null, whereas the ORs for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3). (Purdue MP, Hashibe M, Berthiller J, La Vecchia C, Dal Maso L, Herrero R, Franceschi S, Castellsague X, Wei Q, Sturgis EM, Morgenstern H, Zhang ZF, Levi F, Talamini R, Smith E, Muscat J, Lazarus P, Schwartz SM, Chen C, Neto JE, Wünsch-Filho V, Zaridze D, Koifman S, Curado MP, Benhamou S, Matos E, Szeszenia-Dabrowska N, Olshan AF, Lence J, Menezes A, Daudt AW, Mates IN, Pilarska A, Fabianova E, Rudnai P, Winn D, Ferro G, Brennan P, Boffetta P, Hayes RB. Type of alcoholic beverage and risk of head and neck cancer—a pooled analysis within the INHANCE Consortium. Am J Epidemiol 2009;169:132−142)  

 

LEUKEMIA

Early Chronic Lymphocytic Leukemia Markers

The authors examined whether chronic lymphocytic leukemia (CLL) was always preceded by monoclonal B-cell lymphocytosis (MBL) among 77,469 healthy adults who were enrolled in the PLCO Cancer Screening Trial. Forty-five subjects in whom CLL was diagnosed up to 6.4 years later were identified. Through analysis of peripheral blood samples and use of six-color flow cytometry (with antibodies CD45, CD19, CD5, CD10, kappa, and lambda) and immunoglobulin heavy-chain gene rearrangement by reverse-transcriptase polymerase-chain-reaction assay, the association between MBL and subsequent CLL was determined and the immunoglobulin gene repertoire of the prediagnostic B-cell clones characterized. On the basis of either flow-cytometric or molecular analysis, 44 of 45 patients with CLL had a prediagnostic B-cell clone; in 91% of patients, the presence of the B-cell clone was confirmed by both methods. The presence of immunoglobulin heavy-chain variable (IgVH) genes was determined in 78% of prediagnostic clones. Of these clones, 46% were IgVH3 subgroup genes (including 17% IgVH3-23 genes), and 26% were IgVH4 subgroup genes (including 11% IgVH4-34 genes). Seventy-seven percent of the IgVH sequences had mutations. (Landgren O, Albitar M, Ma W, Abbasi F, Hayes RB, Ghia P, Marti GE, Caporaso NE. B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 2009;360:659−667)

 

LUNG CANCER

Red Meat, Processed Meat, and Meat Mutagens

The association of red meat, processed meat, and meat mutagen intake with lung cancer risk was investigated among 1,903 cases and 2,073 controls in the Environment and Genetics in Lung Cancer Etiology study, a population-based case-control study. Red and processed meat were positively associated with lung cancer risk (highest vs. lowest tertile: ORs = 1.8 and 1.7, respectively); the risks were strongest among never smokers (ORs = 2.4 and 2.5, respectively). Intakes of heterocyclic amines (HCAs) and benzo(a)pyrene were also associated with increased risk. Significant positive associations for both meat groups were found for adenocarcinoma and squamous cell carcinoma but not for small cell carcinoma. (Lam TK, Cross AJ, Consonni D, Randi G, Bagnardi V, Bertazzi PA, Caporaso NE, Sinha R, Subar AF, Landi MT. Intakes of red meat, processed meat, and meat mutagens increase lung cancer risk. Cancer Res 2009;69:932−939)

 

LYMPHOMA

Organochlorine Exposure and Immune Gene Variation

To examine whether an association between organochlorine exposure and non-Hodgkin lymphoma (NHL) is modified by immune gene variation, the authors genotyped 61 polymorphisms in 36 immune genes among 1,172 NHL cases and 982 controls. They examined three exposures with elevated risk: PCB180 (plasma, dust measurements), the toxic equivalency quotient (an integrated functional measure of several organochlorines) in plasma, and alpha-chlordane (dust measurements, self-reported termiticide use). Associations between all three exposures and NHL risk were limited to the same genotypes for IFNG (C-1615T) (TT) and IL4 (5’-UTR, Ex1-168C>T) (CC) (see Figure 3). Associations between PCB180 in plasma and dust and NHL risk were limited to the same genotypes for IL16 (3’-UTR, Ex22+871A>G) (AA), IL8 (T-251A) (TT), and IL10 (A-1082G) (AG/GG). This provides one of the first examples of a potential gene-environment interaction for NHL. (Colt JS, Rothman N, Severson RK, Hartge P, Cerhan JR, Chatterjee N, Cozen W, Morton LM, De Roos AJ, Davis S, Chanock S, Wang SS. Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma. Blood 2009;113:1899−1905)

 

MULTIPLE MYELOMA

Previous Monoclonal Gammopathy of Undetermined Significance

The frequency with which multiple myeloma (MM) is preceded by a premalignant asymptomatic monoclonal gammopathy of undetermined significance (MGUS) was assessed among 77,469 healthy adults enrolled in the PLCO Cancer Screening Trial. Seventy-one individuals who developed MM during the course of the study and had serially collected (up to six) pre-diagnostic serum samples obtained 2–9.8 years prior to MM diagnosis were identified. Using assays for monoclonal (M)-proteins and kappa-lambda free light chains (FLC), MGUS was present in 100%, 98.3%, 97.9%, 94.6%, 100%, 93.3%, and 82.4% at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In about half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. (Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV. Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma: a prospective study. Blood 2009;113:5412–5417)

Familial Risks Associated with MGUS

Using data from Sweden, the authors identified 4,458 MGUS patients, 17,505 population-based controls, and first-degree relatives of patients (n = 14,621) and controls (n = 58,387). Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (RR = 2.8), MM (RR = 2.9), lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia (LPL/WM) (RR = 4.0), and CLL (RR = 2.0). Relatives of patients with IgG/IgA MGUS had a 4.0-fold, 2.9-fold, and 20-fold elevated risk of developing MGUS, MM, and LPL/WM, respectively. Relatives of IgM MGUS patients had a 5.0-fold increased CLL risk and nonsignificant excess MM and LPL/WM risks. The results were very similar when risks were assessed by type of first-degree relative, age at MGUS (above/below 65 years), and sex. Risk of NHL or Hodgkin lymphoma was not increased among MGUS relatives. (Landgren O, Kristinsson SY, Goldin LR, Caporaso NE, Blimark C, Mellqvist UH, Wahlin A, Bjorkholm M, Turesson I. Risk of plasma-cell and lymphoproliferative disorders among 14,621 first-degree relatives of 4,458 patients with monoclonal gammopathy of undetermined significance (MGUS) in Sweden. Blood 2009; Jan 30 [E-pub ahead of print])

 

OVARIAN CANCER

TP53 Gene Variants

The authors assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population included 5,206 invasive ovarian cancer cases (2,829 of which were serous) and 8,790 controls from 13 studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 SNPs in the TP53 region. Significant findings from this discovery phase were followed up for replication in the other OCAC studies. Five SNPs showed significant associations with risk in one or more of the discovery investigations and were followed up by OCAC. Mixed effects analysis confirmed associations with serous invasive cancers for two correlated (r² = 0.62) SNPs: rs2287498 (median per allele OR = 1.30) and rs12951053 (median per allele OR = 1.19). Analyses of other histologic subtypes suggested similar associations with endometrioid but not with mucinous or clear cell cancers. (Schildkraut JM, Goode EL, Clyde MA, Iversen ES, Moorman PG, Berchuck A, Marks JR, Lissowska J, Brinton L, Peplonska B, Cunningham JM, Vierkant RA, Rider DN, Chenevix-Trench G, Webb PM, Beesley J, Chen X, Phelan C, Sutphen R, Sellers TA, Pearce L, Wu AH, Van Den Berg D, Conti D, Elund CK, Anderson R, Goodman MT, Lurie G, Carney ME, Thompson PJ, Gayther SA, Ramus SJ, Jacobs I, Krüger Kjaer S, Hogdall E, Blaakaer J, Hogdall C, Easton DF, Song H, Pharoah PD, Whittemore AS, McGuire V, Quaye L, Anton-Culver H, Ziogas A, Terry KL, Cramer DW, Hankinson SE, Tworoger SS, Calingaert B, Chanock S, Sherman M, Garcia-Closas M; Australian Ovarian Cancer Study Group. Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer. Cancer Res 2009;69:2349−2357)

 

PROSTATE CANCER

Adipokine Gene Effects

Common variants of the IL6, LEP, LEPR, TNF, and ADIPOQ genes were examined among 1,053 prostate cancer cases and 1,053 controls in a large cohort of Finnish men. The authors also examined genotypes in relation to serum insulin, IGF-1, and IGF-1:IGFBP-3 among 196 controls. Variant alleles at three loci (–14858A>G, –13973A>C, –13736C>A) in a potential regulatory region of the LEP gene conferred a 20% reduced risk of prostate cancer. At the –14858A>G locus, heterozygotes and homozygotes for the A allele had an OR for prostate cancer of 0.76 and 0.79, respectively. At 13288G>A, relative to the GG genotype, the AA genotype was associated with a suggestive increased risk of prostate cancer (OR = 1.29; confidence interval = 0.99–1.67; p for trend = 0.05). Polymorphisms in the IL6, LEPR, TNF, and ADIPOQ genes were not associated with prostate cancer. The association of the allelic variants in the LEP gene with prostate cancer risk supports a role for leptin in prostate carcinogenesis. (Moore SC, Leitzmann MF, Albanes D, Weinstein SJ, Snyder K, Virtamo J, Ahn J, Mayne ST, Yu H, Peters U, Gunter MJ. Adipokine genes and prostate cancer risk. Int J Cancer 2009;124:869−876)

Metabolizing Genes and HCAs

Genetic data from the PLCO Cancer Screening Trial were used to determine if prostate cancer risks associated with dietary HCAs (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [PhIP]; 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline [MeIQx]; and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [DiMeIQx]) from cooked meat were modified by SNPs in genes involved in HCA metabolism (CYP1A1, CYP1A2, CYP1B1, GSTA1, GSTM1, GSTM3, GSTP1, NAT1, NAT2, SULT1A1, SULT1A2, and UGT1A loci). The study included 1,126 prostate cancer cases and 1,127 controls selected for GWAS for prostate cancer. The strongest evidence for an interaction was noted between DiMeIQx and MeIQx and the polymorphism rs11102001 downstream of the GSTM3 locus. Among men carrying the A variant, the risk of prostate cancer associated with high DiMeIQx intake was 2.3-fold greater than that with low intake. HCAs may act as promoters of malignant transformation by altering mitogenic signaling. (Koutros S, Berndt Sl, Sinha R, Ma X, Chatterjee N, Alavanja MC, Zheng T, Huang WY, Hayes RB, Cross AJ. Xenobiotic metabolizing gene variants, dietary heterocyclic amine intake, and risk of prostate cancer.  Cancer Res 2009;69:1877−1884)

 

SKIN CANCER

AIDS and Nonkeratinocytic Skin Cancer

The authors linked data from U.S. AIDS and cancer registries to evaluate risk of nonkeratinocytic skin cancers (melanoma, Merkel cell carcinoma (MCC), and appendageal carcinomas, including sebaceous carcinoma [SC]) in 497,142 persons with AIDS. From 60 months before to 60 months after AIDS onset, persons with AIDS had elevated risks of melanoma (standardized incidence ratio [SIR] = 1.3), MCC (SIR = 11), and SC (SIR = 8.1). Risk for appendageal carcinomas increased with progressive time relative to AIDS onset. Risk of these skin cancers was higher among non-Hispanic whites than among other racial/ethnic groups, and melanoma risk was highest among men who had sex with men. Melanoma risk was unrelated to CD4 cell count at AIDS onset. Risks for melanoma and appendageal carcinomas rose with increasing exposure to ultraviolet radiation. The greatly increased risks for MCC and SC suggest an etiologic role for immunosuppression. (Lanoy E, Dores GM, Madeleine MM, Toro JR, Fraumeni JF Jr, Engels EA. Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States. AIDS 2009;23:385−393)

SC and Related Cancer Risks

Sebaceous tumors of the skin occurring in association with an internal malignancy characterize Muir-Torre syndrome (MTS), a variant of hereditary nonpolyposis colon cancer (Lynch syndrome). The authors calculated cutaneous SC incidence rates (IRs) and IR ratios in nine U.S. Surveillance, Epidemiology, and End Results program registries (1973 to 2003). Among 664 cases of cutaneous SC, nearly 90% were diagnosed among whites (IR = 0.11 per 100,000 person-years), with significantly lower IR noted among blacks (IR = 0.04). Whereas eyelid SC IRs demonstrated no sex differences and stabilized in recent years, IRs of non-eyelid SC predominated in men and rose steadily over time. Survivors of SC had a 43% increased risk of subsequent cancer, and risk of SC was 52% higher among survivors of other cancers. Whether before or after SC, the significant excesses of other primary cancers were limited to non-eyelid SC cases. Patterns suggestive of genetic predisposition included more than 20-fold risks for early-onset SC associated with colon, pancreatic, ovarian, or uterine corpus cancers, whereas late-onset SC predisposed to ureter cancer. This population-based study of cutaneous SC revealed an association with a spectrum of early-onset cancers consistent with MTS. (Dores GM, Curtis RE, Toro JR, Devesa SS, Fraumeni JF Jr. Incidence of cutaneous sebaceous carcinoma and risk of associated neoplasms: Insight into Muir-Torre syndrome. Cancer 2008;113:3372−3381)

 

THYROID CANCER

Thyroid Disease after In Utero I-131 Exposure

The authors present estimated risks of thyroid disease from exposure in utero to I-131 fallout from the Chernobyl nuclear accident. They conducted a cross-sectional thyroid screening study from 2003 to 2006 among 2,582 mother-child pairs from Ukraine in which the mother had been pregnant at the time of the accident on April 26, 1986, or up to about two months after the accident, when I-131 fallout was still present (1,494 from contaminated areas, 1,088 in the comparison group). Individual cumulative in utero thyroid dose estimates were derived from estimated I-131 activity in the mother’s thyroid (mean 72 mGy; range 0–3230 mGy). There were seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm identified as a result of the screening. The estimated excess OR per gray for thyroid carcinoma was nonsignificantly elevated (excess OR per gray = 11.66). No radiation risks were identified for other thyroid diseases. Results support  a conservative approach to medical uses of I-131 during pregnancy. (Hatch M, Brenner A, Bogdanova T, Derevyanko A, Kuptsova N, Likhtarev I, Bouville A, Tereshchenko V, Kovgan L, Shpak V, Ostroumova E, Greenebaum E, Zablotska L, Ron E, Tronko M. A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to iodine-131 from Chernobyl fallout. J Clin Endocrinol Metab 2009;94:899−906)

 

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