DESCRIPTION: (Adapted from the Applicant's Abstract): Infection with an
oncogenic type of HPV is etiologic for cervical cancer; however, such
infection is common, and it is important to determine why only a subset of
HPV-infected women develop cervical cancer. Differences between individuals
in the development of, or the failure to repair, DNA damage may be involved
in cervical carcinogenesis by influencing both the likelihood and the
location of HPV integration into human DNA, or by otherwise influencing the
occurrence and persistence of gene mutations. Assessing such differences
between individuals represents an intriguing new avenue of cervical cancer
The investigators propose to conduct an ancillary study within a currently
funded population based case control study to evaluate whether
constitutional genetic instability, as measured by lymphocyte bleomycin
sensitivity, influences risk of invasive cervical cancer. Cases will be
women aged 18-74 who are diagnosed with invasive cervical cancer from
1995-98. Controls will be similarly-aged women selected from the general
population using RDD. Blood samples will be collected for measurement of
lymphocyte bleomycin sensitivity as well as serologic evidence of HPV
infection. In-person interviews will be conducted, and cervical cancer
tissue will be collected to assess the presence of HPV DNA. Invasive
cervical cancer is associated with substantial mortality. Identifying
biomarkers of cervical cancer susceptibility may provide an important means
of distinguishing women who are most likely to develop this disease. This
knowledge may enable the development of therapeutic and preventive
intervention strategies that are targeted to women at high risk. If women
with cervical abnormalities who are at very low risk of disease progression
can be identified, this may allow a reduction in the overtreatment of
cervical disease that is currently believed to occur.
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