Latina province

Unusual north-south migration of 60 000 people from Veneto, Friuli and Emilia Romagna to Latina province area during the 1930s

People were mainly manual workers, farmers and their families involved in land reclamation that drained the marsh area extending from the southern boundaries of Rome to Terracina

From: Tumori, 80: 101-105, 1994

Pool of Italian Cancer Registries(AIRTUM)

http://www.registri-tumori.it/cms/

Latina province cancer registry. Male1 born in northern Italy: observed vs expected cases, standardized incidence ratio (SIR), 95% confidence interval (CI) by site. 1983-87 Site Observed Expected SIR CI Mouth, pharynx 15 9.45 159 89-262 Esophagus 3 2.70 111 22-324 Stomach 24 17.61 136 87-203 Colon 14 13.76 102 55-171 Rectum 9 8.99 100 46-190 Liver 11 6.63 166 83-297 Biliary tract 2 3.08 65 7-234 Pancreas 8 5.16 155 67-305 Larynx 11 7.55 146 72-260 Lung 93 60.37 154 124-189 A Bone 0 0.33 0 0-1125 Connective tissue 2 1.78 112 12-405 Skin (melanomas) 2 1.79 111 12-403 Skin (carcinomas) 52 35.03 148 111-195 B Prostate 26 13.81 188 123-276 C Testis 0 0.47 0 0-785 Bladder 31 26.05 119 81-169 Kidney, urinary tract 6 3.71 162 59-352 Central nervous system 6 2.95 303 74-442 Thyroid 1 0.36 281 4-1562 Unspecified site, metastases 8 4.30 186 80-366 Unknown origin 3 2.72 110 22-322 Non-Hodgkin lymphomas 6 5.08 118 43-257 Hodgkin’s lymphoma 2 1.47 136 15-491 Multiple mieloma 1 1.63 61 1-342 Leukaemias 12 6.53 184 95-321 All site 354 249.36 142 127-157 d 1Age ≥55 years a p<0.05; b p<0.01; c p<0.005; d p<0.001. From: Tumori, 80: 101-105, 1994

Number of subjects to be followed until the age of 84 years to detect one incident cancer, by site and sex. Pool of Italian Cancer Registries. Period 2005-2007

SITE MALE FEMALE Upper respiratory and digestive tract cancers 36 166 Stomach 28 57 Colorectum 10 17 Liver 34 95 Pancreas 51 64 Lung 9 35 Melanoma of skin 43 58 Non melanoma skin cancer 9 15 Breast 553 8 Corpus uteri - 47 Ovary - 74 Prostate 7 - Kidney and other urinary cancer 36 84 Bladder 13 69 Thyroid 152 56 Non-Hodgkin lymphoma 45 61 All cancers except non melanoma skin cancer 2 2 From: “I numeri del cancro in Italia 2011”.

www.registritumori.it/PDF/AIOM2011/I_numeri_del_cancro_2011.pdf (modified)

Number of subjects to be followed until the age of 84 years to observe one death by cancer site and sex. Pool of Italian Cancer Registries. Period 2005-2007

SITE MALE FEMALE Upper respiratory and digestive tract cancers 71 344 Stomach 38 82 Colorectum 25 45 Liver 40 112 Pancreas 50 67 Lung 10 44 Melanoma of skin 269 513 Breast 32 Corpus uteri 897 Ovary 104 Prostate 33 Kidney and other urinary cancer 94 244 Bladder 51 306 Thyroid 1184 897 Hodgkin’s lymphoma 110 152 All cancers except non melanoma skin cancer 3 6

From: “I numeri del cancro in Italia 2011”. www.registritumori.it/PDF/AIOM2011/I_numeri_del_cancro_2011.pdf (modified)

Five most frequently diagnosed cancer and percentage on the overall number of cases (excl. non-melanoma skin cancer). Pool of Italian cancer registries. Period 2005-2007, by gender and age-classes

From: http://www.registri-tumori.it/cms/node/2172. (modified)

Males Females0-49 50-69 70+ 0-49 50-69 70+

1° Testis(11%)

Prostate(22%)

Prostate(21%)

Breast(40%)

Breast(35%)

Breast(20%)

2° Melanoma(10%)

Colorectum (15%)

Lung(17%)

Thyroid(13%)

Colorectum (13%)

Colorectum (17%)

3° Colorectum(8%)

Lung(14%)

Colorectum (15%)

Melanoma (8%)

Corpus uteri(7%)

Lung(7%)

4° Non-Hodgkin lymphoma

(8%)

Bladder (10%)

Bladder (11%)

Cervix uteri(6%)

Lung(6%)

Stomach (6%)

5° Thyroid (6%)

Upper respiratory and digestive tract

(5%)

Stomach (6%)

Colorectum(5%)

Thyroid(4%)

Pancreas(5%)

Melanoma: Italy. Incidence rates (Eu. Stand. Per 100 000) by geographical area and sex. Pool of Italian Cancer Registries. 2005-2007

Nord Center South

14.31

12.27

6.44

13.54

12.18

6.11

Males Females

From: www.registri-tumori.it/PDF/AIOM2011/I_numeri_del_cancro_2011_+_errata_corrige.pdf (modified)

Skin melanoma. Relative survival (%), 2000-2004. Male & female. Pool of 31 cancer registries. Italy

1 year 3 years 5 years

96

8985

From: Epidemiol Prev 2011; 35 (5-6) suppl 3: 1-200 (Modified)

Incidence and mortality cancer trends, 1998-2005. Annual percent change. Pool of Italian cancer registriesSite Males Females

Incidence Mortality Incidence Mortality Upper respiratory and digestive tract cancers -3.2 -3.4 +1.4 +1.4

Oesophagus -1.9 -2.5 -0.1 +1.0

Stomach -3.3 a) -2.1 b) -8.2

-3.5 -3.5

Colorectum +0.8 -0.5 +0.6 -1.4

Liver -0.7 -1.2 -1.0 -1.3

Gallbladder -0.2 +03 -2.0 -0.2

Pancreas +0.3 -0.1 c) +2.1 d) -0.2

+0.3

Lung -2.6 -2.3 +1.3 +1.5

Melanoma of skin +3.8 +2.6 +1.9 -0.3

Non melanoma skin cancer -0.7 +0.8 -0.1 +5.7

Mesothelioma +1.1 +1.3

Soft tissue cancer +2.9 -1.4 +0.1 -1.1

Kaposi’s sarcoma -4.8 -6.0

Breast e) +3.4 f) -0.4

-1.0

Cervix uteri -3.4 -3.8

Corpus uteri +0.9 +0.3

Ovary -1.2 -1.4

Prostate a) +7.3 b) +3.4

-1.7

Testis +4.5 +1.6

Kidney and other urinary cancer +0.3 -0.4 +1.1 +0.5

Bladder -0.8 -1.9 -0.4 -1.6

Brain -0.3 +0.1 +0.7 +1.0

Thyroid c) +10.0 d) + 4.2

-0.9 +7.1 -3.4

Hodgkin’s lymphoma +1.1 -0.3 +2.1 -2.1

Non-Hodgkin lymphoma e) +4.2 f) -1.1

-3.2 -0.2 -2.2

Multiple myeloma -2.0 -0.6 -0.9 -0.3

Leukaemia -2.9 -1.9 -1.4 -0.4

All cancers except non melanoma skin cancer +0.3 -1.7 +0.3 -0.8

Statistically significant increase of the estimated annual percent change Statistically significant decrease of the estimated annual percent change

Years: a)1998-2003, b)2003-2005; c)1998-2001, d)2001-2005; e)1998-2000, f)2000-2005.

From: www.registri-tumori.it/PDF/AIRTUM2009Trend/E&P33_4-5S1_19_trend.pdf (modified)

Prevalence, Italy, 01.01.2006. Number of subjects by cancer site. Male & female. Pool of Italian Cancer Registries.

From: www.registri-tumori.it/cms/?q=Rapp2010 (Modified)

Leukaemias

Cervix uteri

Larynx

Stomach

Trachea, bronchus and lung

SKIN MELANOMA

Thyroid

Kidney and other urinary organ

Corpus uteri

Non-Hodgkin Lymphoma

Head and neck

Prostate

Bladder

Colon and rectum

Female breast

51378

53361

54650

69225

75365

80802

81131

84413

91689

95250

106727

216716

223533

296687

522235

*cancer site with N. subjects ≥ 50 000)

World burden of skin cancers: summary results for the year 2000

Disease *DALYs (000) Deaths Incident cases

Melanoma 690.248 65 161 211 921

Squamous cell carcinoma 161.892 13 534 2 883 037

Basal cell carcinoma 57.983 3245 10 532 711

Total 910.123 81 940 13 627 669

*disability-adjusted life year

From: www.who.int/uv/publications/solaradgbd/en/index.html

Risk Factors for cutaneous melanoma

Constitutional features Phototype (I, II, III) Hair colour (Red, Blond, Light Brown) Skin colour (Light colour) Eye colour (Blue, Green, Hazel) Naevi (Atypical naevi, number of

naevi) Freckles (High density)

Behavioural features Sun exposure (Intermittent, Chronic) Sun exposure (In childhood, In

Adulthood) Use of indoor tanning equipment

Actinic damage indicators Family history

Personal history

Melanoma prevention practices

• Seeking shade• Wearing broad spectrum sunscreen• Covering up with a shirt and/or a hat• Wearing sunglasses

Early detection pratices

• Skin self-examinations• Examinations by medical professionals

Skin cancer risk factors in childhood: findings of a survey in an Italian area characterized by an atypical migration (A)Objective: to evaluate the association of different phenotypes with sun sensitivity factors, sun protection behavior and ethnicity in school-age children.Design: cross sectional study in the framework of a survey of children using a self-administered questionnaire.Setting and participants: 35 412 children attending primary schools in the provinces of Latina and Rome, located in the Lazio region (Italy), in the 1998-2001 time period.

From: Ramazzotti V et al. Epidemiol Prev. 2009 Jan-Apr;33(1-2):45-50. (Modified)

Skin cancer risk factors in childhood: findings of a survey in an Italian area characterized by an atypical migration (B)Results«FOTO positive» phenotype was directly associated with:•the tendency to sunburn (OR 4.64; 95% CI 4.39-4.89)•the presence of freckles on the face (OR 1.65; 95% CI 1.55-1.77)•the presence of naevi on the left forearm (OR 1.18; 95% CI 1.12-1.25)•the number of grandparents born in northern areas (OR 1.54; 95% CI 1.15-2.07, for four northern grandparents versus none)•the residence in Latina Province (OR 1.13; 95% CI 1.07-1.20)•the use of sunscreens (OR 1.70; 95% CI 1.55-1.88)«FOTO positive» phenotype was inversely associated with•the male sex (OR 0.91; 95% CI 0.86-0.96)•the increase of school-class level (OR 0.66; 95% CI 0.61-0.72, for the highest versus the lowest school-class level)•the ability to tan (OR 0.38; 95% CI 0.34-0.42)

From: Ramazzotti V et al. Epidemiol Prev. 2009 Jan-Apr;33(1-2):45-50. (Modified)

Sun protection behavior in primary school children: comparison between pre- andpost-intervention results. Valencia, Spain; 2007 - 2008

_______________________________________________________________________________________ Characteristics Baseline (%) Post-intervention (%) p value _______________________________________________________________________________________ Sun avoidance at midday Never/rarely/sometimes 65 80 0.01 Often/always 35 20 Sunscreens Sometimes/often 31 28 0.61 Always 69 72 High-SPF sunscreens Rarely/sometimes/often 28 23 0.80 Always 72 77 High-SPF, all days Rarely/sometimes/often 47 43 0.99 Always 53 57 Timing sunscreens 20 min before sun exposure 63 70 0.42 At/during exposure 37 30 Sunscreen re-application Rarely/sometimes 47 37 0.28 Often/always 53 63 Hats Never/rarely/sometimes 37 45 0.23 Often/always 63 55 T-Shirt Never/rarely/sometimes 39 47 0.99 Often/always 61 52 Sunglasses Never 45 36 0.69 Rarely/sometimes/often/always 55 64 Sunburns in the last summer No 81 91 0.15 Yes 19 9 ____________________________________________________________________________________ Cercato MC, Nagore E, Ramazzotti V, Sperduti I, Guillén C. Improving sun-safe knowledge, attitude and behaviour in parents of primary school children: a pilot study. J Cancer Educ. 2013 Mar;28(1):151-7

CDKN2A

• 5% - 10% of all melanomas are hereditary– Of those

Up to 40% are explained by mutations in theCyclin-dependent kinase inhibitor 2°

CDKN2A

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

In USA individuals positive for a mutation in CDKN2A have a

76% estimated lifetime risk of developing melanoma

(lifetime risk in the general population: 2%)

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

MC1R

Variants in melanocortin- 1 receptor (MC1R) gene

confer risk of melanoma(to a lesser degree of a mutation in CDKN2A)

Risk by MC1R is greater in individuals withdarker

hairhyesskin colorCancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Use of genetic testing and counseling for melanoma risk: effects (a)

Will individuals who test positive for genetic mutations increase their sun avoidance and skin examination behaviors?

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Use of genetic testing and counseling for melanoma risk: effects (b)

Will individuals who test negative (or inconclusive) for mutations be less vigilant because of a reassurance effect?

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Aspinwall LG et al. CDKN2A genetic test reporting improves early detection intentions and practices in high-risk melanoma

families.

• Total body skin examinations by medical professional• Skin self-examinations

In n. 77 individuals with: CDKN2A (+) and personal history of melanoma; CDKN2A (+) and no personal history of melanoma; CDKN2A (-);

This group reported a significant increase in monthly skin self-examination intentions and behaviors at follow up

Cancer Epidemiol Biomarkers Prev 2008; 17(6): 1510 - 1519

Bergernmar M et al. Family members’perceptions of genetic testing for malignant melanoma – A prospective interview study.

In 11 unaffected members of melanoma-prone familiesMeasurement of:

Anxiety and depression Risk perception Sun-related habits

1. Before2. At disclosure3. Six months after disclosure CDKN2A Genetic test Results4. On year post-disclosure

Disclosure of genetic test results did not change perceived risk for melanoma

Eur J Oncol 2002; 3(11): 653-654

Glanz KL et al. Melanoma Genetic Testing, Counseling, and Adherence to Skin Cancer Prevention and Detection Behaviors

(A)

Randomized control trialTwo groups of individuals (73 adults) in hereditary melanoma families

A. Individuals enrolled in melanoma families (a. three or more cases of melanoma on the same side of family; b. two or more cases in first degree relatives)

B. All participants completed a full body skin examination of moles and provided a blood and/or buccal swab sample for CDKN2A and MC1R genotyping

Intervention group: offering genetic counseling and test results (35 individuals) Control group: not offering genetic counseling and test results (38 individuals)

1. Baseline Survey (see specific items)

2. Genetic counseling session with a genetic counselor

3. Follow-up survey (for months after)

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Glanz KL et al. Melanoma Genetic Testing, Counseling, and Adherence to Skin Cancer Prevention and Detection Behaviors (B)

Aims: to investigate the effect of offering genetic counseling and testing on:

Behavior Attitudes Perceived risk of melanoma Current and intended sun avoidance/protection Skin examination behaviors

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Differences between intervention and control groups at baseline

p-valueAge NS% High risk NS% Previously diagnosed melanoma NS% Ever getting genetic testing NS% With a family member who had ever had genetic testing NS__________________________________________________________________

I C% Female 80.0 57.9 0.04% BMI overweight/obese 40.0 65.80.03% Family history of melanoma (other than self) 25.7 52.6 0.03% Very good or excellent self rated health 88.5 52.70.01Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Changes in Behaviors in Behaviors and Attitudes from Baseline to Follow-Up (1 a)

Prevention & Detection Behaviors p-value_______________________________________________________________Sun Protection Habits NSWear Sunscreen NSWear Sunglasses NSSeek Shade NSWear a Hat NSLimit Hours in the Sun NSSkin Examination by a Medical Professional NSSun Exposure: Weekday NSSun exposure: Weekend NSSunburn Frequency NS

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Changes in Behaviors in Behaviors and Attitudes from Baseline to Follow-Up (2)

Perceptions and Beliefs p-value______________________________________________________________Perceived Skin Cancer Risk NSPerceived Benefits of Sun Protection NSPerceived Barriers to Sun Protection NSAwareness of Genetic Counseling NSPerceived Benefits of Genetic Counseling NS

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Changes in Behaviors and Attitudes from Baseline to Follow-Up (1 b)

Prevention & Detection Behaviors Score Mean SD p-value

I C______________________________________________________________a)Wear Shirt (1-4) Baseline 2.80 3.00

Follow-up 2.60 2.39 0.047_____________________________________________________________________

b)Skin Self - Examination (1-4) Baseline 1.89 1.71 Follow-up 1.23 1.84 0.002

_____________________________________________________________________a) Higher scores = greater frequency of the behaviorb) Lower scores = more recent self examination

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14

Conclusions

Feedback of CDKN2A and MC1R genotype“does not appear to decrease sun protection behaviors”

also among families without known pathogenic CDKN2A mutations

Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):607-14