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Other highlights in the January 18 JNCI

Journal of the National Cancer Institute

HIV Infection Associated with Increased Risk of High-Grade Cervical Squamous Intraepithelial Lesions (HSILs)
Women infected with HIV types 1 and 2 may have a higher risk of HSIL than HIV-negative women, according to a new study in Senegalese women.

Stephen E. Hawes, Ph.D., of the University of Washington in Seattle, and colleagues studied a cohort of 627 women with and without HIV types 1 and/or 2 and/or high-risk human papillomavirus (HPV) infection in Senegal, West Africa. They followed the women for a mean of 2.2 years with evaluations every 4 months.

They found that women infected with both HIV and a high-risk HPV type were at greatest risk of developing a cervical cancer precursor called HSIL. HIV-positive women with low CD4 cell counts and high plasma HIV RNA levels were at increased risk of HSIL. The authors conclude that an increased risk of developing HSIL among HIV-infected women is primarily associated with increased HPV persistence that may be related to immunosuppression induced by HIV infection.

Contact: Clare Hagerty, 206-685-1323,

Sex Hormones Not a Useful Predictor of Breast Cancer Risk
Sex hormone levels in the blood are not associated with the risk of developing breast cancer in postmenopausal women who are in high-risk groups, according to a new study.

Several studies have suggested that increased levels of the sex hormones estradiol and testosterone and decreased levels of a protein that binds to sex hormones called sex hormone-binding globulin are associated with an increased risk of breast cancer in postmenopausal women. Although tamoxifen is commonly used to treat breast cancer in postmenopausal women, one study suggested that raloxifene, a selective estrogen receptor modulator (SERM), was associated with a larger reduction in breast cancer risk among women with high levels of estradiol.

Mary S. Beattie, M.D., of the University of California in San Francisco, and colleagues examined the levels of sex hormones estradiol and testosterone, and sex hormone-binding globulin in the blood plasma of 135 postmenopausal women with breast cancer and 275 postmenopausal control women who had been treated with tamoxifen or placebo as part of a breast cancer prevention trial. The authors sought to determine whether sex hormone levels are associated with breast cancer risk, and whether breast cancer risk reduction varied by sex hormone level among women on tamoxifen, which is also a SERM.

Their results showed that levels of sex hormones were not associated with breast cancer risk in these women and cannot be used as a predictor for breast cancer risk or determine who would most benefit from tamoxifen treatment. Tamoxifen had the same effect on breast cancer risk in women with high and low levels of estradiol. The authors suggest that the study should be repeated in other populations with a high risk of developing breast cancer.

Contact: Nancy Chan, 415-885-7277,

Increasing Penetrance of BRCA2 Increases Mutations Over Time, Study Shows
The incidence of breast cancer before 70 years in Icelandic women who carry a specific mutation in the BRCA2 gene increased fourfold between 1920 and 2002, according to a new study.

About 7% of Icelandic women diagnosed with breast cancer carry the specific BRCA2 mutation, including 24% of women diagnosed with breast cancer before the age of 40.

Laufey Tryggvadóttir, managing director of the Icelandic Cancer Registry in Reykjavik, and colleagues analyzed tissue samples from 847 patients diagnosed with breast cancer between 1921 and 1985 in Iceland. Eighty-eight patients carried the BRCA2 mutation. The authors found that the incidence of breast cancer in the mutation carriers increased from 19% to 72% between 1920 and 2002. A similar magnitude of increase was seen in relatives of the breast cancer patients who did not carry the mutation and in the general Icelandic population. In the same time period, the risk of death for BRCA2 mutation carriers increased from 13% to 27%. The authors suggest that the main cause of the large increase in breast cancer incidence, both in carriers of the BRCA2 mutation and in women without the mutation, is likely related to changing lifestyle during the last several decades.

Contact: Laufey Tryggvadóttir, Icelandic Cancer Registry, 354-690-3766,

Variation in IGF1 Gene Associated with Risk of Prostate Cancer
A new study suggests that genetic variation in the insulin-like growth factor 1 (IGF1) gene may be associated with the risk of prostate cancer.

Earlier studies have shown that men with the highest circulating levels of IGF-I, the product of the IGF1 gene, are at an increased risk of developing prostate cancer. It was not known, however, if variations in the IGF1 gene were associated with an increased risk of developing prostate cancer.

Matthew Freedman, M.D., at the Dana-Farber Cancer Institute and Broad Institute of Harvard and MIT in Cambridge, and colleagues examined specific variations in the IGF1 gene called single nucleotide polymorphisms (SNPs) largely derived from a public SNP database in 4610 individuals with and without prostate cancer. They identified two specific polymorphisms on the IGF1 gene that were associated with an increased risk of prostate cancer. "Our results suggest that inherited variation in IGF1 may play a role in prostate cancer risk," they write.

Contact: Bill Schaller, Dana-Farber Cancer Institute, 617-632-5357,

Study Examines the Association Between Diabetes Mellitus and Risk of Colorectal Cancer
People with diabetes may have a higher risk of developing colorectal cancer, according to a new study.

Diets high in fat, energy, protein, red meat, and carbohydrates and low in fruit and vegetables are associated with an increased risk of colorectal cancer. Studies have suggested that this risk may be related to the insulin pathway, which regulates blood sugar levels, and is associated with diabetes mellitus.

Adeline Seow, M.D., of the National University of Singapore, and colleagues examined diet and cancer incidence in a lean population of 63,257 Singapore Chinese men and women between ages 45 and 74, with initial evaluation from April 1993 to December 1998. Researchers found 636 cases of colorectal cancer by December 2002. Diagnosis of diabetes mellitus was associated with an increased risk of colorectal cancer in men and women. The incidence of colorectal cancer among people with diabetes was 208.9 cases per 100,000 people and was 140.2 cases per 100,000 people among nondiabetics. Persons who reported having physician-diagnosed diabetes when recruited into the study had a 50% higher risk of developing colorectal cancer subsequently, compared with non-diabetics.

The authors write, "In summary, we observed that diabetes mellitus was a risk factor for colorectal cancer in Singapore Chinese and that this association was statistically significant among those with high intake of total calories and low levels of physical activity, both of which are independent predictors of high insulin levels. Our results provide support for an association between hyperinsulemia and colorectal cancer, even in a relatively lean population."

Contact: Fun Yip, (65) 6516-1374,

Study Examines IGF1 Gene, HNPCC, and Colorectal Cancer Risk
A new study has shown that having a low number of specific sequences of the IGF1 gene called CA-repeats is associated with an increased risk of colorectal cancer in people with the disorder hereditary nonpolyposis colorectal cancer (HNPCC). The study was completed by Marsha L. Frazier, Ph.D., of the M. D. Anderson Cancer Center in Houston, and colleagues. People with HNPCC are at an elevated risk of several cancers, including colorectal cancer. The new study is the first to show that variants of the IFG1 gene may be associated with the risk of a hereditary form of cancer.

Contact: Laura Sussman, M.D. Anderson Cancer Center, 713-745-2457,

Also in the January 18 JNCI:
HPV Testing a Cost-Effective Strategy for Women with Equivocal Cervical Screening Results:


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