The incidence of
cutaneous malignant melanoma has increased dramatically in white skinned
populations throughout the world over past decades. The state of Queensland has the highest incidence of
melanoma in the world with life time incidences of 1 in 13 males and a in 16 females. Over the past 20 years, the principal
investigators have conducted several large scale studies into the molecular
genetics and genetic epidemiology of melanoma and its risk factors,
particularly nevus density and pigmentation. Recently, the focus has been on
the roles of sun exposure and known melanoma susceptibility genes (CDKN2A and
CDK4) and pigmentation genes (MC1R). We now have the largest and
best-described population-based sample of melanoma cases and their families
in the world. We wish to extend these resources and perform new analyses to
elucidate the pathways from genotype and environmental risk factors, via
intervening phenotypic variables to melanoma.
The investigators for
this National Institutes of Health (NIH) funded study of the genetics of
melanoma have been studying the molecular genetics and genetic epidemiology
of melanoma and its risk factors for around 20 years. This study will follow
up the participants of previous studies. There are 6 groups of respondents,
based on their previous participation in the following studies:
The Queensland Familial Melanoma Project (QFMP)
Beginning in 1994, the
QFMP was undertaken by Nick Martin, Joanne Aitken
and others. This is the largest family and twin study study
of CMM yet conducted in an unselected,
geographically-defined population, and includes the largest population-based
sample of melanoma cases in the world. Family history information was
obtained from all 12,014 Queensland residents with a first primary CMM diagnosed between
1982-1990 (sourced from the Queensland Cancer registry). Further
detailed information on melanoma history and standard risk factors was sought
from all twins, familial CMM cases, and their relatives; and from a sample of
non-familial CMM cases and their relatives, to give a final sample of
1,912 families. Of these families, 1,403 families contain a single member
with CMM, 415 contain two, 67 contain
three, and 27 families contain 4 or more cases. These families are the basis
for the three groups refered
to as high, medium and low risk. Each family has a proband, who is the principal contact for the family. Members of
these families have been bled and asked questionnaires in three separate
waves between about 1994 and now.
Risk Melanoma Study - Nick Hayward
Some families included in
a study by Nick Hayward of high risk melanoma families (3+cases) that began
around 1985 overlap with families in the QFMP.
Undertaken by David
Whiteman in 1995, this matched (1:3) case control study sought to determine
whether plausible determinants of adult CMM were associated with CMM in childhood. 61 cases of CMM in children under 15 years were
notified to the QCR from January 1987 to June 30, 1994. Controls were randomly selected
from schools and matched for sex and age. 31 cases were bled.
A population based
case-control study was carried out to examine the risk factors for melanoma
in adolescents. All 250 cases of melanoma diagnosed in adolescents aged 15-19
years, between 1987 to 1994 and notified to the QCR
were included in the study. Melanoma cases were matched to a control by sex,
age and region of residence. 201 cases were bled.
Men over 50 study
This study by David
Whiteman was of 150 men over 50 diagnosed with melanoma. Participants were
not asked to give a blood sample.
1b. Specific aims
follow up 1,912 families of the Queensland Familial Melanoma Project
(QFMP) in order to update survival status and risk factor information.
obtain blood samples from all melanoma cases, one unaffected sibling of proband, and available parents of all high familial
risk families, intermediate risk families, and a 50% sample of low risk
follow-up probands and families from three overlapping substudies of melanoma in children, adolescents and
older men using the same interview and blood collection protocols as
augment these samples with previously collected DNA samples from 600 age matched, sex, ethnically matched community
controls for whom camparible risk factor data
identify all common intronic single nucleotide polymorphisms (SNPs) of the CDKN2A gene, and exonic
SNPs of the P gene by sequencing these genes
in 100 subjects of diverse melanoma risk and pigmentation type.
type by allele specific oligonucleotide hybridisation (ASO) newly identified
and previously discovered SNPs in genes of the
cell cycle axis (CDKN2A, CDKN2B, CDK4), and pigmentation axis (MC1R, P).
fine map a major quantitative trait locus (QTL) affecting nevus density
linked to CDKN2A in the Brisbane Twin Nevus Study (BTNS)
extend a 10cM genome scan of the BTNS to 800 twin families.
We will interview
all probands, all affected sibs and one unaffected sib closest in age to the
family for whom we obtain a proband sample, we shall attempt to obtain a
sample from one unaffected sibling, all available parents and all other
affected relatives. In the absence of parents, we will aim to obtain samples
from 2 unaffected sibs per unavailable parent.
Click on the links below to access the following publications in PDF
(If you do not have Adobe Acrobat Reader you can download it here)
G, Duffy DL, Eldridge A, Grace M, Mayne C, O'Gorman L, Aitken
JF, Neale MC, Hayward NK, Green AC, Martin NG: A
major quantitative-trait locus for mole density is linked to the familial
melanoma gene CDKN2A: a maximum-likelihood combined linkage and association
analysis in twins and their sibs. Am J Hum Genet 1999 Aug;65(2):483-92.
JS, Duffy DL, Box NF, Aitken JF, O'Gorman LE, Green
AC, Hayward NK, Martin NG, Sturm RA: Melanocortin-1 receptor polymorphisms
and risk of melanoma: Is the association explained solely by pigmentation
phenotype? American Journal of Human Genetics 66:176-186, 2000.
F Box, David L Duffy, Rachel E. Irving, Anne Russell, Wei
Chen, Lyn R GrifĂths,▓ Peter G Parsons, Adele C Green, and Richard A Sturm.
Melanocortin-1 Receptor Genotype is a Risk Factor for Basal and Squamous Cell
Carcinoma. Journal of Investigative Dermatology 116(2):1-7, Feb, 2001
J, Millar D, Goldman A, Heenan P, Stark M, Eldon M,
Clark S, Martin NG, Hayward NK: Lack of genetic and epigenetic changes in
Cdkn2a in melanocytic nevi. Journal of Investigative Dermatology 117(2):383-384,
NF, Duffy DL, Chen W, Stark M, Martin NG, Sturm RA, Hayward NK: MC1R genotype
modifies risk of melanoma in families segregating CDKN2A mutations. American
Journal of Human Genetics 69(4):765-773, Oct 2001.
Siskind V, Aitken
J, Green A, Martin, NG: Sun exposure and interaction with family history in
risk of melanoma in Queensland, Australia. International Journal of Cancer
97(1): 90-95, Jan 2002.
Pamela M. et al. High frequency of BRAF mutations in nevi. Published online
25 November 2002. Doi:10.1038/ng1054
from the Queensland Familial Melanoma Project
from the Adolescent Melanoma Study and
from the Childhood Melanoma Study and
from the 50+ Men Melanoma Study
and their families