Research Highlights - 2002 and 2003
Below are highlights of research reported by grantees supported by the Epidemiology and Genetics Research Program (EGRP). We can't begin to capture all the research contributions of our grantees and apologize for this. (The names that appear in boldface are those of the principal investigators of the EGRP-supported grants cited in the published reports.)
- Some Breast Cancers May Be Due to Inherited Susceptibility to Hormones at Puberty
- Lobular Breast Carcinoma on the Increase
- Obesity, Tamoxifen, and Outcomes in Women with ER-Positive Early-Stage Breast Cancer
- Estrogen Associated With Increased Risk for Breast Cancer in Asian Women
- Electromagnetic Fields Not Associated With Risk for Breast Cancer
- Dietary Changes Associated With Colorectal Cancer in Mexican Americans
- Loss of DNA Repair Capability in Colorectal Cancer Patients Increases With Age
- New Lead Found on Genetics of Familial Colorectal Cancer
- Searching for Reasons for Elevated Rates of Colon Cancer Among African Americans
- The Dietary Folate and Lung Cancer Connection Explored
- DNA Repair Gene Polymorphisms and Cigarette Smoking Interaction Found
- XPA Polymorphism Associated With Decreased Risk for Lung Cancer
- GST Detoxifying Gene Variant Linked to Lung Cancer in Men, Younger Individuals
- A Y Chromosome May Play Role in Risk of Prostate Cancer Among Asians
- New Clues Found on Genetic Susceptibility for Aggressive Prostate Cancer
- The Hunt for Prostate Cancer Susceptibility Genes Proves Difficult
- Mononucleosis Related to Epstein-Barr Virus and Risk for Hodgkin's Lymphoma
- Explanation Found for HPV 16's Strong Association With Cervical Cancer
- Oncogenic Human Papilloma Virus Infection and Progression to Cervical Cancer
Some Breast Cancers May Be Due to Inherited Susceptibility to Hormones at Puberty
Thomas Mack, M.D., M.P.H., and Ann Hamilton, Ph.D., of the University of Southern California at Los Angeles, have found that certain breast cancers may be linked to an unusual inherited sensitivity to the ovarian hormones that flood the body at puberty. Among identical female twins who both were diagnosed with breast cancer, the twin who began menstruating earlier was more than five times as likely as the other twin to develop breast cancer first. Females who started menstruating before age 12 were especially susceptible to getting breast cancer first within the pair. In contrast, some of the well-known risk factors for breast cancer, such as late age at first pregnancy and at menopause, were associated with increased risk for breast cancer only among pairs of identical and fraternal twins in which one twin had breast cancer, but not among those in which both twins had the disease. These findings suggest that there may be another pathway to development of breast cancer that is related to genetic susceptibility. In some genetically susceptible women, elevated ovarian hormone levels at puberty might affect breast cells when they are still immature and vulnerable, and the damage may manifest itself as cancer decades later.
Hamilton AS, Mack TM. Puberty and genetic susceptibility to breast cancer in a case control study in twins. N Engl J Med 2003 Jun 5;348(23):2313-22.
Lobular Breast Carcinoma on the Increase
Research has suggested that combined estrogen and progestin hormone replacement therapy (CHRT) may be associated with increased risk for breast cancer, particularly invasive lobular breast carcinoma. The finding is noteworthy because lobular carcinoma is more difficult to detect by physical examination and mammography. Janet Daling, Ph.D., of Fred Hutchinson Cancer Research Center, and colleagues now report that incidence rates for lobular carcinoma increased steadily from 1987 to 1999 (the proportion increasing from 9.5 to 15.6 percent of all breast cancer cases), while rates for ductal carcinoma remained constant. The increase in rates for lobular carcinoma was most pronounced for women ages 50 and older.
In further research focusing on postmenopausal women, Daling and others found that the risk for invasive lobular breast carcinoma and other histologic types of breast cancer increased among women who were currently taking CHRT. Unopposed estrogen replacement therapy (ERT) was not associated with increased risk for any histologic type of breast cancer. Neither CHRT nor ERT substantially increased the risk for ductal breast carcinoma. They also found that incidence rates for lobular carcinoma in situ have steadily increased over the past 25 years among postmenopausal women. These findings suggest the need for further research to explore reasons for these trends.
Li CI, Anderson BO, Daling JR, Moe RE. Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA 2003 Mar 19;289(11):1421-4.
Daling JR, Malone KE, Doody DR, Voigt LF, Bernstein L, Coates RJ, Marchbanks PA, Norman SA, Weiss LK, Ursin G, Berlin JA, Burkman RT, Deapen D, Folger SG, McDonald JA, Simon MS, Strom BL, Wingo PA, Spirtas R. Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma. Cancer 2002 Dec 15;95(12):2455-64.
Li CI, Anderson BO, Daling JR, Moe RE. Changing incidence of lobular carcinoma in situ of the breast. Breast Cancer Res Treat 2002 Oct;75(3):259-68.
Obesity, Tamoxifen, and Outcomes in Women with ER-Positive Early-Stage Breast Cancer
James Dignam, Ph.D., of The University of Chicago, and colleagues have found that obesity is not associated with an increased risk of recurrence among women with early-stage, hormone-responsive breast cancer, and does not appear to decrease the effectiveness of the drug tamoxifen. This finding supports use of tamoxifen for women of all body types. Earlier studies suggested that risk for breast cancer recurrence and death was increased for obese women compared with lean women, but these studies included women with different stages of breast cancer. Further, obesity was found to be associated with increased risk for contralateral breast cancer, other new primary cancers, and overall mortality. The findings are from analysis of data on 3,385 women enrolled in a National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized, placebo-controlled clinical trial (B-14) evaluating the effectiveness of tamoxifen following surgery for lymph node-negative, estrogen receptor (ER)-positive breast cancer.
Dignam JJ, Wieand K, Johnson KA, Fisher B, Xu L, Mamounas EP. Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 2003 Oct 1;95(19):1467-76.
Estrogen Associated With Increased Risk for Breast Cancer in Asian Women
epidemiologic studies on estrogen and breast cancer have been conducted
in white populations. A new study assessed the association in Asian women
whose levels of estrogen are substantially lower than those of white women.
Herbert Yu, M.D., Ph.D., of Yale University, and Wei Zheng,
Ph.D., of Vanderbilt University, and colleagues found that elevated
sex hormones in the circulation, both estrogen and androgen, were associated
with increased risk for breast cancer even in the Asian population with
relatively low sex hormone levels. The finding suggests that the role
of endogenous sex hormones in breast cancer is the same in the Asian population
as in white women. Dr. Yu is pictured far left, and Dr. Zheng is to his
Yu H, Shu XO, Shi R, Dai Q, Jin F, Gao YT, Li BD, Zheng W. Plasma sex steroid hormones and breast cancer risk in Chinese women. Int J Cancer 2003 May 20;105(1):92-7.
Electromagnetic Fields Not Associated With Risk for Breast Cancer
M. Cristina Leske, M.D., M.P.H., of Stony Brook University, and colleagues found no indication that electromagnetic fields (EMFs) increase risk for breast cancer in a study that included comprehensive measurements of EMFs in and around the outside of the homes of study participants, and data collected by interview. The findings offer reassurance to individuals who have been concerned about a possible link between EMFs and risk for breast cancer. The results are consistent with an earlier NCI-funded study of EMFs and breast cancer that included in-home measurements, adding further weight to the strength of the evidence.
Schoenfeld ER, O'Leary ES, Henderson K, Grimson G, Kabat GC, Ahnn S, Kaune WT, Gammon MD, Leske MC. Electromagnetic fields and breast cancer on Long Island: A case-control study. Am J Epidemiol 2003 July 158(1):47-58.
Dietary Changes Associated With Colorectal Cancer in Mexican Americans
Kristine Monroe, Ph.D., of the University of Southern California at Los Angeles, and Laurence Kolonel, M.D., Ph.D., of the University of Hawaii, and colleagues examined changes in dietary practices that might be consistent with the increasing incidence of colorectal cancer in the Mexican-American migrant population of Los Angeles. Some food traditions were retained by Mexican Americans, but the dietary changes resulting from acculturation were significant and support an association between colorectal cancer risk and certain dietary components, especially alcohol as a risk factor and vegetables as protective factors. The scientists found an 11 percent and 9 percent decrease in calorie-adjusted mean intake of vegetables, excluding legumes, in U.S.-born men and women, respectively, compared with Mexican-born study participants. The decline in mean vegetable intake was lower, 18 percent and 15 percent, respectively, when legumes were included in the vegetable category. There also was a decrease in intake of nonstarch polysaccharides (dietary fiber) from vegetables, 13 percent in men and 10 percent in women. The study is based on data from the EGRP-funded Multiethnic Cohort Study.
Monroe KR, Hankin JH, Pike MC, Henderson BE, Stram DO, Park S, Nomura AM, Wilkens LR, Kolonel LN. Correlation of dietary intake and colorectal cancer incidence among Mexican-American migrants: The Multiethnic Cohort Study. Nutr Cancer 2003;45(2):133-47.
Loss of DNA Repair Capability in Colorectal Cancer Patients Increases With Age
The frequency of loss of expression of the DNA repair gene hMLH1 in colorectal cancer patients is strongly associated with increasing age, according to research by Noralane Lindor, M.D., of the Mayo Clinic, and colleagues. The loss was most pronounced in tumors of female patients, and in tumors that originated on the right side of the colon. Loss of gene expression in right-sided tumors occurred in almost 50 percent of patients who were more than 90 years of age. The age-related trend also was seen in males and in tumors that originated in the left colon. The findings suggest the need for additional research on possible environmental or genetic reasons for the damage, and the possibility of developing a non-invasive method to screen for the disease. The study population was drawn from the EGRP-funded Colon Cancer Family Registries.
Kakar S, Burgart LJ, Thibodeau SN, Rabe KG, Petersen GM, Goldberg RM, Lindor NM. Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age. Cancer 2003 Mar 15;97(6):1421-7.
New Lead Found on Genetics of Familial Colorectal Cancer
New research points to a chromosomal region responsible for forms of familial colorectal cancer unrelated to well known hereditary forms of the disease. Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) account for about 5 percent of colorectal cancers, but an additional 20 percent of individuals with the cancer report having a first-degree relative with the disease. Whole genome scans were conducted to test for genetic linkage in 53 kindreds in which two or more siblings were diagnosed with colorectal by age 65 or younger, or who had advanced colon adenomas of greater than one centimeter, or showed high-grade dysplasia. Kindreds with FAP, HNPCC, or other known hereditary forms of the cancer were excluded.
Sanford Markowitz, M.D., Ph.D., of Case Western Reserve University, and colleagues found that a single locus (9q22.2-31.2) can contribute to susceptibility in patients with familial colorectal cancer unrelated to known syndromes. Additional research will be needed to determine if the findings are generalizable to larger populations.
Wiesner GL, Daley D, Lewis S, Ticknor C, Platzer P, Lutterbaugh J, MacMillen M, Baliner B, Willis J, Elston RC, Markowitz SD. A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2. Proc Natl Acad Sci 2003 Oct 28;100(22):12961-5.
Searching for Reasons for Elevated Rates of Colon Cancer Among African Americans
African Americans have the highest incidence rate for colon cancer among U.S. racial ethnic groups, and the reasons are largely unknown. The North Carolina Colon Cancer Study, which is a large case-control study with similar numbers of African Americans and whites, provides a unique opportunity to search for clues. Jessie Satia-Abouta, Ph.D., and Robert Sandler, M.D., M.P.H., of the University of North Carolina at Chapel Hill, and colleagues found that total energy intake consistently was positively associated with increased risk for colon cancer for both whites and African Americans. However, associations with individual macronutrients (fat, carbohydrate, protein) varied somewhat by race and adjustment for energy intake.
For African Americans, saturated fat was associated with increased risk for colon cancer when risk estimates were not adjusted for total energy intake, and dietary fiber was statistically significantly associated with reduced risk both with and without adjustment for total energy intake. These findings, coupled with those from an earlier study specific to African Americans, suggest that a high-fiber, low saturated fat diet may decrease risk for colon cancer for this group. For whites, when risk estimates were not adjusted for total energy, high intakes of total energy and most macronutrients were positively associated with increased risk for colon cancer, but the associations largely disappeared when total energy was taken into account. Alcohol intake was not associated with increased risk for colon cancer in either racial group.
In other analyses on this study population, vitamins E and C from food sources were associated with a reduction in risk for colon cancer among African Americans when comparing individuals with intake in the highest quartile to those in the lowest quartile. Beta-carotene, vitamin C, and calcium were associated with a reduction in risk for colon cancer among whites when comparing individuals in the highest to the lowest quartile. This research suggests that micronutrients may be independently associated with 30-70 percent reductions in risk for colon cancer in the two groups.
Satia-Abouta J, Galanko JA, Potter JD, Ammerman A, Martin CF, Sandler RS; North Carolina Colon Cancer Study. Associations of total energy and macronutrients with colon cancer risk in African Americans and Whites: results from the North Carolina Colon Cancer Study. Am J Epidemiol 2003 Nov 15;158(10):951-62.
Satia-Abouta J, Galanko JA, Martin CF, Potter JD, Ammerman A, Sandler RS. Associations of micronutrients with Colon Cancer risk in African Americans and whites: results from the North Carolina Colon Cancer Study. Cancer Epidemiol Biomarkers Prev 2003 Aug;12(8):747-54.
The Dietary Folate and Lung Cancer Connection Explored
Folate deficiency increasingly is believed to be associated with altered DNA methylation and synthesis and disruption of DNA repair, which might explain reports of a link between folate deficiency and risk of different types of cancer. Qingyi Wei, M.D., Ph.D., and Margaret Spitz, M.D., M.P.H., of The University of Texas M.D. Anderson Cancer Center, and colleagues found low dietary intake of folate to be associated with suboptimal DNA repair capability (as measured by the host cell reactivation assay). Studying a cancer-free population, they found that individuals in the lowest tertile of dietary folate intake had a greater reduction in DNA repair capability than those in the upper tertile of intake. The association also was more pronounced in individuals who did not use folate supplements than in those who did.
In other research, Hongbing Shen, Ph.D., Dr. Spitz, and colleagues found that dietary folate may protect against lung cancer in an analysis of data on 470 lung cancer patients who were former smokers and 472 former smoker controls. Former smokers were studied to avoid confounding bias from smoking. There was an inverse dose-response relationship between increasing intake of dietary folate and decreased risk of lung cancer. The association was especially apparent among those who drank alcoholic beverages, were former heavy smokers, reported having a family history of lung cancer, and those who did not take folate supplements. Dietary folate intake above the control median level was associated with a 40 percent decreased risk of lung cancer. If confirmed by other studies, the findings could have important public health implications for use of folate supplements or diet modification to increase intake of the vitamin in at-risk populations.
Wei Q, Shen H, Wang LE, Duphorne CM, Pillow PC, Guo Z, Qiao Y, Spitz MR. Association between low dietary folate intake and suboptimal cellular DNA repair capacity. Cancer Epidemiol Biomarkers Prev 2003 Oct;12(10):963-9.
Shen H, Wei Q, Pillow PC, Amos CI, Hong WK, Spitz MR. Dietary folate intake and lung cancer risk in former smokers: A case-control analysis. Cancer Epidemiol Biomarkers Prev 2003 Oct;12(10):980-6.
DNA Repair Gene Polymorphisms and Cigarette Smoking Interaction Found
David Christiani, M.D., of Harvard School of Public Health, and colleagues have published the first report demonstrating gene-smoking interaction between the joint effects of the DNA repair genes XRCC1 and ERCC2 and cumulative cigarette smoking exposure in risk for lung cancer. The magnitudes of these interactions appear to be associated with the number of variant alleles of the ERCC2 polymorphisms Asp312ASN and Lys751Gln and the XRCC1 Arg399Gln polymorphism. How cigarette smoking changes the DNA repair capability of the polymorphisms is not known.
Zhou W, Liu G, Miller DP, Thurston SW, Xu LL, Wain JC, Lynch TJ, Su L, Christiani DC. Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2003 Apr;12(4):359-65.
XPA Polymorphism Associated With Decreased Risk for Lung Cancer
Margaret Spitz, M.D., M.P.H., of the University of Texas M.D. Anderson Cancer Center (pictured elsewhere on the page), and colleagues have shown that an XPA polymorphism modulates nucleotide excision repair (NER) capacity and is associated with decreased risk for lung cancer, particularly among ever smokers. Individuals with the AG substitution in the 5-end of the non-coding region had a reduced risk of lung cancer. This pattern was statistically significant for Caucasians and Mexican Americans, but not for African Americans.
Wu X, Zhao H, Wei Q, Amos CI, Zhang K, Guo Z, Qiao Y, Hong WK, Spitz MR. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 2003 Mar;24(3):505-9.
GST Detoxifying Gene Variant Linked to Lung Cancer in Men, Younger Individuals
Research suggests that polymorphisms of glutathion transferases (GST), which are involved in detoxification of carcinogens, may alter the ability to detoxify and increase risk for certain cancers. Research by Xifeng Wu, M.D., Ph.D., and Margaret Spitz, M.D., M.P.H., of the University of Texas M.D. Anderson Cancer Center, and colleagues indicates that the GSTP1 exon 6 polymorphism is associated with increased risk for lung cancer especially in men, younger individuals, and ever smokers. This finding suggests that having the polymorphism may be an important genetic susceptibility factor. The scientists did not find that the exon 5 polymorphism, which also has been implicated in lung cancer, to be associated with increased risk for the disease.
Wang Y, Spitz MR, Schabath MB, Ali-Osman F, Mata H, Wu X. Association between glutathione S-transferase p1polymorphisms and lung cancer risk in Caucasians: a case-control study. Lung Cancer 2003 Apr;40(1):25-32.
Sunlight-Induced DNA Damage Associated With Increased Risk for Melanoma
Qingyi Wei, M.D., Ph.D., of the University of Texas M.D. Anderson Cancer Center, and colleagues have found that reduced DNA repair capability caused by ultraviolet light is associated with increased risk for melanoma. They also found a dose-response relationship between the DNA damage and risk for melanoma. This hospital-based case-control study is the largest and first epidemiologic study to show that reduced DNA repair capability may play a role in causation of sunlight-induced melanoma. Sunlight exposure, particularly intermittent bursts of exposure early in life, is directly associated with risk for melanoma. A relatively small proportion of individuals exposed to sunlight develop melanoma, however, suggesting that genetic susceptibility plays a role in causation of the cancer.
Wei Q, Lee JE, Gershenwald JE, Ross MI, Mansfield PF, Strom SS, Wang LE, Guo Z, Qiao Y, Amos CI, Spitz MR, Duvic M. Repair of UV light induced DNA damage and risk of cutaneous malignant melanoma. J Natl Cancer Inst 2003 Feb 19;95(4):308-15
Some Medications Associated With Decreased Risk of Non-Hodgkin's Lymphoma
The incidence of non-Hodgkin's lymphoma has been increasing steadily worldwide, and little is known about risk factors for the disease. Some studies have suggested that certain medications may have a protective effect against the cancer, but drug exposures were assessed in different ways in the studies. In research drawing upon the drug-dispensing records from community pharmacies and hospital records in the Netherlands, Elizabeth Holly, Ph.D., M.P.H., of the University of California at San Francisco, and colleagues report an inverse relationship between occurrence of non-Hodgkin's lymphoma and use of antihistamine medications (histamine2 blockers) and analgesics among women. They also found reductions in risk among women that were not statistically significant and may have been due to chance for other drugs studied. However, the inverse associations tended to increase with increasing duration of use of the drugs, suggesting reason for further study. The other drugs studied included nonsteroidal anti-inflammatory drugs, cholesterol-lowering drugs, and antibiotics.
Beiderbeck AB, Holly EA, Sturkenboom MC, Coebergh JW, Stricker BH, Leufkens HG. Prescription medications associated with a decreased risk of non-Hodgkin's lymphoma. Am J Epidemiol 2003 Mar 15;157(6):510-6.
A Y Chromosome May Play Role in Risk of Prostate Cancer Among Asians
Silvia Paracchini, Ph.D., of the University of Oxford, Laurence Kolonel, M.D., Ph.D., of the University of Hawaii, and Brian Henderson, M.D., of the University of Southern California at Los Angeles, and colleagues investigated the role of the Y chromosome in prostate cancer in a case-control study nested within the Multiethnic Cohort Study. The analysis included data on 930 prostate cancer cases and 1,208 controls. The men were African American, white, Latino, and Japanese. Only the Y lineage O3, which was present almost exclusively in the Japanese study participants, was associated with a 63 percent increased risk of prostate cancer. The risk was modified by age and severity of disease. Japanese men under age 65 who had the Y lineage O3 had nearly a fourfold increased risk of developing severe prostate cancer. If studies of other Japanese or Asian populations yield similar findings, the scientists suggest that a systematic evaluation of the genetic changes in this lineage is warranted. (Drs. Kolonel and Henderson are pictured elsewhere on the page.)
Paracchini S, Pearce CL, Kolonel LN, Altshuler D, Henderson BE, Tyler-Smith C. A Y chromosomal influence on prostate cancer risk: The multi-ethnic cohort study. J Med Genet 2003 Nov;40(11):815-9.
New Clues Found on Genetic Susceptibility for Aggressive Prostate Cancer
A variety of genetic epidemiologic studies are investigating how better to identify men at risk for aggressive prostate cancer. These studies have important implications for improving diagnosis and treatment, and for identifying ways to prevent the disease. Previous research has suggested that chromosome 19q harbors a gene for aggressiveness of prostate cancer. Research by Stephen Thibodeau, Ph.D., of the Mayo Clinic, and colleagues confirms this finding and provides strong evidence of the association. The scientists analyzed genome scan data from men in 161 families among whom there was a family history of prostate cancer. The study also suggested that chromosome 4q may be involved in tumor aggressiveness.
In other research, Sara Strom, Ph.D., of the University of Texas M.D. Anderson Cancer Center, and colleagues found that the presence of a certain allele was strongly associated with younger age at diagnosis of prostate cancer. This "A" allele of the cell cycle regulating gene cyclin D1 also has been associated with early onset colorectal cancer and poorer prognosis for lung cancer. Still other research by Richard Everson, M.D., Ph.D., of Wayne State University, and colleagues indicates that certain polymorphisms in the androgen receptor and in genes that influence androgen metabolism are associated with increased risk for being diagnosed with prostate cancer and with more aggressive disease.
Slager SL, Schaid DJ, Cunningham JM, McDonnell SK, Marks AF, Peterson BJ, Hebbring SJ, Anderson S, French AJ, Thibodeau SN. Confirmation of linkage of prostate cancer aggressiveness with chromosome 19q. Am J Hum Genet 2003 Mar;72(3):759-62.
Sanchez-Ortiz RF, Yamamura Y, Frazier ML, Babalan RJ, Troncoso P, Pettaway CA, Strom S. Relationship between cyclin D1 polymorphism and age at diagnosis of prostate cancer. Proc Annu Meet Am Assoc Cancer Res 2003.
Powell IJ, Land SJ, Zhou J, Sun Y, Dey J, Patel NP, Sakr WA, Hughes MR, Everson RB. Influence of androgen receptor and androgen metabolism polymorphisms on prostate cancer prognosis after prostactectomy in an ethnically diverse population. Proc Annu Meet Am Assoc Cancer Res 2003.
The Hunt for Prostate Cancer Susceptibility Genes Proves Difficult
Despite strong evidence for the existence of prostate cancer susceptibility genes, the search for such genes has been frustrating. The International Consortium for Prostate Cancer Genetics (ICPCG) demonstrates how difficult this research has been in a review of eight genome-wide linkage searches for chromosomal regions associated with development of the cancer. The ICPCG, with William Isaacs, Ph.D., of Johns Hopkins University as principal investigator, is funded through a grant from EGRP.
The review was based on 1,293 families with multiple cases of prostate cancer, but even with these numbers, no chromosomal region was found to be especially promising. Eleven linkage peaks with LOD scores in excess of 2 were identified, but no chromosomal region was reported as significant at this level by more than one study. Further, only one of these linkage peaks corresponded to a peak previously suggested by another group.
The ICPCG's review shows that prostate cancer is genetically complex, and that combined analyses of large family sets will be needed to evaluate reliably the linkage evidence. The consortium plans such analyses with a combined dataset on more than 2,000 families, which will provide the statistical power to detect genes of much smaller effect, and allow a more reliable evaluation of subsets based on family history, disease aggressiveness, and co-occurrence of other types of cancer.
Easton DF, Schaid DJ, Whittemore AS, Isaacs WJ. Where are the prostate cancer genes? A summary of eight genome wide searches. Prostate 2003 Dec 1;57(4):261-9.
Mononucleosis Related to Epstein-Barr Virus and Risk for Hodgkin's Lymphoma
Infectious mononucleosis related to infection with Epstein-Barr virus (EBV) is associated with an increased risk for Hodgkin's lymphoma in young adults. This finding is from a study of more than 60,000 young adults in two Danish cohorts of patients who tested positive for infectious mononucleosis. Mads Melbye, M.D., Ph.D., of the Statens Serum Institut in Copenhagen, and colleagues found no evidence of an increased risk of EBV-negative Hodgkin's lymphoma following infectious mononucleosis. However, there was a 4-fold increased risk of EBV-positive Hodgkin's lymphoma after infectious mononucleosis. The estimated median incubation time from mononucleosis to diagnosis of EBV-positive Hodgkin's lymphoma was 4.1 years.
This study makes a convincing connection among infectious mononucleosis, EBV, and the development of Hodgkin's disease. The risk of Hodgkin's disease after infectious mononucleosis is low about 1 case per 1,000 persons with EBV-related mononucleosis, suggesting that other co-factors are involved.
Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang JS, Madsen M, Rosdahl N, Konradsen HB, Storm HH, Melbye M. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med 2003 Oct 2;349(14):1324-32.
Explanation Found for HPV 16's Strong Association With Cervical Cancer
Human papillomavirus (HPV) 16, which is responsible for about one-half of all cervical cancers, appears to be more successful in escaping immune surveillance than other HPV types. The findings may explain why HPV 16 plays a major role in causing cervical cancer. Howard Strickler, M.D., M.P.H., of the Albert Einstein College of Medicine, and colleagues compared the prevalence and incidence of different HPV types among HIV-positive women who had varying levels of T cells, an indicator of immune status.
Strickler HD, Palefsky JM, Shah KV, Anastos K, Klein RS, Minkoff H, Duerr A, Massad LS, Celentano DD, Hall C, Fazzari M, Cu-Uvin S, Bacon M, Schuman P, Levine AM, Durante AJ, Gange S, Melnick S, Burk RD. Human papillomavirus type 16 and immune status in human immunodeficiency virus-seropositive women. J Natl Cancer Inst 2003 Jul 16;95(14):1062-71.
Oncogenic Human Papilloma Virus Infection and Progression to Cervical Cancer
Precursor lesions of the cervix detected by cytology persist longer and are more likely to progress in women who have oncogenic types of human papilloma virus infections (HPV) than in women with non-oncogenic types of HPV infections or in uninfected women. These findings reported by Eduardo Franco, Dr.P.H., of McGill University, and colleagues, suggest that testing for HPV in women who have abnormal PAP smears may help identify patients who would benefit from more intensive follow-up and chemopreventive treatment. Other patients might be followed at longer intervals and potentially could avoid invasive diagnostic and therapeutic procedures.
Schlecht NF, Platt RW, Duarte-Franco E, Costa MC, Sobrinho JP, Prado JC, Ferenczy A, Rohan TE, Villa LL, Franco EL. Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia. J Natl Cancer Inst 2003 Sep 3;95(17):1336-43.
Clinic-Based Study Designs Give More Accurate Estimates of Penetrance
Alice Whittemore, Ph.D., and Gail Gong, Ph.D., of Stanford University School of Medicine, used computer simulations to compare the performance of two study designs based on family data for estimating the disease risk associated with mutations of known disease-susceptibility genes. The scientists found that clinic-based designs, where families are ascertained because they meet certain criteria for multiple disease occurrence in the family, yielded more accurate estimates than did population-based designs, where families are sampled through population-based registries of affected individuals. The reason may be that clinic-based designs include more identified mutation carriers. The study was conducted with assistance from the EGRP-funded Cancer Family Registries.
Gong G, Whittemore AS. Optimal designs for estimating penetrance of rare mutations of a disease susceptibility gene. Genet Epidemiol 2003 Apr;24(3):173-80.
Two papers on research methods may be of interest to epidemiologists: